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  1. Quercetin Prevents Diastolic Dysfunction Induced by a High-Cholesterol Diet: Role of Oxidative Stress and Bioenergetics in Hyperglycemic Rats

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    Rodrigo L. Castillo

    2018-01-01

    Full Text Available Alterations in cardiac energy metabolism play a key role in the pathogenesis of diabetic cardiomyopathy. Hypercholesterolemia associated with bioenergetic impairment and oxidative stress has not been well characterized in the cardiac function under glycemic control deficiency conditions. This work aimed to determine the cardioprotective effects of quercetin (QUE against the damage induced by a high-cholesterol (HC diet in hyperglycemic rats, addressing intracellular antioxidant mechanisms and bioenergetics. Quercetin reduced HC-induced alterations in the lipid profile and glycemia in rats. In addition, QUE attenuated cardiac diastolic dysfunction (increased E:A ratio, prevented cardiac cholesterol accumulation, and reduced the increase in HC-induced myocyte density. Moreover, QUE reduced HC-induced oxidative stress by preventing the decrease in GSH/GSSG ratio, Nrf2 nuclear translocation, HO-1 expression, and antioxidant enzymatic activity. Quercetin also counteracted HC-induced bioenergetic impairment, preventing a reduction in ATP levels and alterations in PGC-1α, UCP2, and PPARγ expression. In conclusion, the mechanisms that support the cardioprotective effect of QUE in rats with HC might be mediated by the upregulation of antioxidant mechanisms and improved bioenergetics on the heart. Targeting bioenergetics with QUE can be used as a pharmacological approach to modulate structural and functional changes of the heart under hypercholesterolemic and hyperglycemic conditions.

  2. Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic β-Cells Function

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    Catalina Carrasco-Pozo

    2017-01-01

    Full Text Available Cholesterol plays an important role in inducing pancreatic β-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic β-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV. Sulforaphane also attenuated the cholesterol-induced activation of the NFκB pathway, normalizing the expression of pro- and anti-inflammatory cytokines. In addition, it also inhibited the decrease in sirtuin 1 expression and greatly increased Pgc-1α expression in Min6 cells. Sulforaphane increased the expression of antioxidant enzymes downstream of the Nrf2 pathway and prevented lipid peroxidation induced by cholesterol. The antioxidant and anti-inflammatory properties of sulforaphane and its ability to protect and improve mitochondrial bioenergetic function contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction. Our data provide a scientifically tested foundation upon which sulforaphane can be developed as nutraceutical to preserve β-cell function and eventually control hyperglycemia.

  3. Statins Prevent Dextrose-Induced Endoplasmic Reticulum Stress and Oxidative Stress in Endothelial and HepG2 Cells.

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    Kojanian, Hagop; Szafran-Swietlik, Anna; Onstead-Haas, Luisa M; Haas, Michael J; Mooradian, Arshag D

    Statins have favorable effects on endothelial function partly because of their capacity to reduce oxidative stress. However, antioxidant vitamins, unlike statins, are not as cardioprotective, and this paradox has been explained by failure of vitamin antioxidants to ameliorate endoplasmic reticulum (ER) stress. To determine whether statins prevent dextrose-induced ER stress in addition to their antioxidative effects, human umbilical vein endothelial cells and HepG2 hepatocytes were treated with 27.5 mM dextrose in the presence of simvastatin (lipophilic statin that is a prodrug) and pravastatin (water-soluble active drug), and oxidative stress, ER stress, and cell death were measured. Superoxide generation was measured using 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride. ER stress was measured using the placental alkaline phosphatase assay and Western blot of glucose-regulated protein 75, c-jun-N-terminal kinase, phospho-JNK, eukaryotic initiating factor 2α and phospho-eIF2α, and X-box binding protein 1 mRNA splicing. Cell viability was measured by propidium iodide staining. Superoxide anion production, ER stress, and cell death induced by 27.5 mM dextrose were inhibited by therapeutic concentrations of simvastatin and pravastatin. The salutary effects of statins on endothelial cells in reducing both ER stress and oxidative stress observed with pravastatin and the prodrug simvastatin suggest that the effects may be independent of cholesterol-lowering activity.

  4. Inhibition of macrophage oxidative stress prevents the reduction of ABCA-1 transporter induced by advanced glycated albumin.

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    de Souza Pinto, Raphael; Castilho, Gabriela; Paim, Bruno Alves; Machado-Lima, Adriana; Inada, Natalia M; Nakandakare, Edna Regina; Vercesi, Aníbal Eugênio; Passarelli, Marisa

    2012-05-01

    We investigated the role of aminoguanidine and benfotiamine on the inhibition of reactive oxygen species (ROS) generation in macrophages induced by advanced glycated albumin (AGE-albumin) and its relationship with cell cholesterol homeostasis, emphasizing the expression of the ATP binding cassette transporter A-1 (ABCA-1). AGE-albumin was made by incubating fatty acid-free albumin with 10 mM glycolaldehyde. ROS production and ABCA-1 protein level were determined by flow cytometry in J774 macrophages treated along time with control (C) or AGE-albumin alone or in the presence of aminoguanidine or benfotiamine. Mitochondrial function was evaluated by oxygraphy. Compared to C-albumin, AGE-albumin increased ROS production in macrophages, which was ascribed to the activities of NADPH oxidase and of the mitochondrial system. Mitochondrial respiratory chain activity was reduced in cells incubated with AGE-albumin. ROS generation along time was associated with the reduction in macrophage ABCA-1 protein level. Aminoguanidine prevented ROS elevation and restored the ABCA-1 content in macrophages; on the other hand, benfotiamine that promoted a lesser reduction in ROS generation was not able to restore ABCA-1 levels. Inhibition of oxidative stress induced by AGE-albumin prevents disturbances in reverse cholesterol transport by curbing the reduction of ABCA-1 elicited by advanced glycation in macrophages and therefore may contribute to the prevention of atherosclerosis in diabetes mellitus.

  5. Geranylgeranylacetone prevents stress-induced decline of leptin secretion in mice.

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    Itai, Miki; Kuwano, Yuki; Nishikawa, Tatsuya; Rokutan, Kazuhito; Kensei, Nishida

    2018-01-01

    Geranylgeranylacetone (GGA) is a chaperon inducer that protects various types of cell and tissue against stress. We examined whether GGA modulated energy intake and expenditure under stressful conditions. After mice were untreated or treated orally with GGA (0.16 g per kg body weight per day) for 10 days, they were subjected to 2-h restraint stress once or once a day for 5 consecutive days. GGA administration did not affect corticosterone response to the stress. Restraint stress rapidly decreased plasma leptin levels in control mice. GGA significantly increased circulating leptin levels without changing food intake and prevented the stress-induced decline of circulating leptin. However GGA-treated mice significantly reduced food intake during the repeated stress, compared with control mice. GGA prevented the stress-induced decline of leptin mRNA and its protein levels in epidydimal adipose tissues. We also found that GGA decreased ghrelin mRNA expression in gastric mucosa before the stress, whereas GGA-treated mice recovered the ghrelin mRNA expression to the baseline level after the repeated stress. Leptin and ghrelin are now recognized as regulators of anxiety and depressive mood. Our results suggest that GGA may regulate food intake and relief stress-induced mood disturbance through regulating leptin and ghrelin secretions. J. Med. Invest. 65:103-109, February, 2018.

  6. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

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    Natalia Nuño-Lámbarri

    2016-01-01

    Full Text Available Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.

  7. Free cholesterol accumulation impairs antioxidant activities and aggravates apoptotic cell death in menadione-induced oxidative injury.

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    Lee, Waisin; Xu, Mingjing; Li, Yue; Gu, Yong; Chen, Jianping; Wong, Derek; Fung, Peter C W; Shen, Jiangang

    2011-10-01

    Although the relationship between hypercholesterolemia and oxidative stress has been extensively investigated, direct evidence regarding to the roles of cholesterol accumulation in the generations of reactive oxygen species (ROS) and apoptotic cell death under oxidative stress is lack. In this study, we investigated productions of superoxide anions (O(2)(-)) and nitric oxide (NO), and apoptotic cell death in wild type Chinese hamster ovary (CHO) cells and cholesterol accumulated CHO cells genetically and chemically. Oxidative stress was induced by menadione challenge. The results revealed that abundance of free cholesterol (FC) promoted menadione-induced O(2)(-) and NO productions. FC accumulation down-regulated eNOS expression but up-regulated NADPH oxidases, and inhibited the activities of superoxide dismutase (SOD) and catalase. Treatment of menadione increased the expressions of iNOS and qp91 phox, enhanced the activities of SOD and catalase in the wild-type CHO cells but inhibited the activity of glutathione peroxidase in the cholesterol accumulated CHO cells. Moreover, FC abundance promoted apoptotic cell death in these cells. Taken together, those results suggest that free cholesterol accumulation aggravates menadione-induced oxidative stress and exacerbates apoptotic cell death. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Evaluation of lipid profile and oxidative stress in STZ-induced rats treated with antioxidant vitamin

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    Danielle Ayr Tavares de Almeida

    2012-08-01

    Full Text Available The present study investigated the effect of supplementation of vitamin E on streptozotocin (STZ-induced diabetic rats by measuring blood glucose, changes in body weight, food and water intake, lipid profile, serum urea and creatinine level, and antioxidant enzyme activity. Male Wistar rats were divided into four groups: control rats (GI; rats receiving vitamin E (GII; STZ-induced diabetic rats (GIII and STZ-induced diabetic rats treated with vitamin E (GIV. Vitamin E reduced (p<0.05 blood glucose and urea, improved the lipid profile (decreased the serum levels of total cholesterol, LDL cholesterol, VLDL cholesterol and triacylglycerols, and increased HDL cholesterol and increased total protein in STZ-induced diabetic rats (GIV. Vitamin prevented changes in the activity of SOD and GSH-Px and in the concentration of lipid hydroperoxide. These results suggested that vitamin E improved hyperglycaemia and dyslipidaemia while inhibiting the progression of oxidative stress in STZ-induced diabetic rats.

  9. Effect of increased magnesium intake on plasma cholesterol, triglyceride and oxidative stress in alloxan-diabetic rats.

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    Olatunji, L A; Soladoye, A O

    2007-06-01

    Cardiovascular disorders are the primary causes of morbidity and mortality in patients with diabetes mellitus (DM). Agents that improve lipid profile and reduce oxidative stress have been shown to reduce the ensuing risk factors. In the present study, we investigated whether increased magnesium intake could improve hyperglycaemia, dyslipidaemia, and reduce oxidative stress in alloxan-induced diabetic rats. Male Wistar rats were divided into non-diabetic (ND), diabetic (DM) and diabetic fed on a high magnesium diet (DM-Mg) groups. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) were used as markers of oxidative stress. Plasma levels of ascorbic acid, magnesium and calcium were also determined. Diabetes was induced by injecting alloxan (100 mg/kg B.W). The fasting blood glucose levels were significantly lower in the DM-Mg rats than in the DM rats. Plasma total cholesterol, triglyceride, TBARS levels were significantly higher while plasma HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, ascorbic acid levels were significantly lowered in DM rats compared with the ND rats. Increased intake of magnesium significantly abrogated these alterations. There were no significant differences in the plasma levels of magnesium and calcium between the DM and ND groups. However, plasma levels of magnesium but not calcium were significantly elevated in DM-Mg rats when compared with other groups. In conclusion, these results suggest that diet rich in magnesium could exert cardioprotective effect through reduced plasma total cholesterol, triglyceride, oxidative stress and ameliorated HDL-cholesterol/total cholesterol ratio as well as increased plasma ascorbic acid and magnesium in diabetic rats.

  10. Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: An updated mini-review

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    Erdi Sozen

    2017-08-01

    Full Text Available Endoplasmic reticulum (ER is the major site of protein folding and calcium storage. Beside the role of ER in protein homeostasis, it controls the cholesterol production and lipid-membrane biosynthesis as well as surviving and cell death signaling mechanisms in the cell. It is well-documented that elevated plasma cholesterol induces adverse effects in cardiovascular diseases (CVDs, liver disorders, such as non-alcoholic fatty liver disease (NAFLD, non-alcoholic steatosis hepatitis (NASH, and metabolic diseases which are associated with oxidative and ER stress. Recent animal model and human studies have showed high cholesterol and ER stress as an emerging factors involved in the development of many metabolic diseases. In this review, we will summarize the crucial effects of hypercholesterolemia and ER stress response in the pathogenesis of CVDs, NAFLD/NASH, diabetes and obesity which are major health problems in western countries. Keywords: Endoplasmic reticulum stress, High cholesterol, Cardiovascular diseases, Non-alcoholic fatty liver disease, Non-alcoholic steatosis hepatitis

  11. Transcranial Stimulation of the Dorsolateral Prefrontal Cortex Prevents Stress-Induced Working Memory Deficits.

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    Bogdanov, Mario; Schwabe, Lars

    2016-01-27

    Stress is known to impair working memory performance. This disruptive effect of stress on working memory has been linked to a decrease in the activity of the dorsolateral prefrontal cortex (dlPFC). In the present experiment, we tested whether transcranial direct current stimulation (tDCS) of the dlPFC can prevent stress-induced working memory impairments. We tested 120 healthy participants in a 2 d, sham-controlled, double-blind between-subjects design. Participants completed a test of their individual baseline working memory capacity on day 1. On day 2, participants were exposed to either a stressor or a control manipulation before they performed a visuospatial and a verbal working memory task. While participants completed the tasks, anodal, cathodal, or sham tDCS was applied over the right dlPFC. Stress impaired working memory performance in both tasks, albeit to a lesser extent in the verbal compared with the visuospatial working memory task. This stress-induced working memory impairment was prevented by anodal, but not sham or cathodal, stimulation of the dlPFC. Compared with sham or cathodal stimulation, anodal tDCS led to significantly better working memory performance in both tasks after stress. Our findings indicate a causal role of the dlPFC in working memory impairments after acute stress and point to anodal tDCS as a promising tool to reduce cognitive deficits related to working memory in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Working memory deficits are prominent in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Similar working memory impairments have been observed in healthy individuals exposed to acute stress. So far, attempts to prevent such stress-induced working memory deficits focused mainly on pharmacological interventions. Here, we tested the idea that transcranial direct current stimulation of the dorsolateral prefrontal

  12. Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

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    Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

    2017-03-15

    It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Hepatocyte Growth Factor Reduces Free Cholesterol-Mediated Lipotoxicity in Primary Hepatocytes by Countering Oxidative Stress

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    Mayra Domínguez-Pérez

    2016-01-01

    Full Text Available Cholesterol overload in the liver has shown toxic effects by inducing the aggravation of nonalcoholic fatty liver disease to steatohepatitis and sensitizing to damage. Although the mechanism of damage is complex, it has been demonstrated that oxidative stress plays a prominent role in the process. In addition, we have proved that hepatocyte growth factor induces an antioxidant response in hepatic cells; in the present work we aimed to figure out the protective effect of this growth factor in hepatocytes overloaded with free cholesterol. Hepatocytes from mice fed with a high-cholesterol diet were treated or not with HGF, reactive oxygen species present in cholesterol overloaded hepatocytes significantly decreased, and this effect was particularly associated with the increase in glutathione and related enzymes, such as γ-gamma glutamyl cysteine synthetase, GSH peroxidase, and GSH-S-transferase. Our data clearly indicate that HGF displays an antioxidant response by inducing the glutathione-related protection system.

  14. 2-heptyl-formononetin increases cholesterol and induces hepatic steatosis in mice

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    Andersen, Charlotte; Schjoldager, Janne Gram; Tortzen, Christian

    2013-01-01

    Consumption of isoflavones may prevent adiposity, hepatic steatosis, and dyslipidaemia. However, studies in the area are few and primarily with genistein. This study investigated the effects of formononetin and its synthetic analogue, 2-heptyl-formononetin (C7F), on lipid and cholesterol metabolism...... in C57BL/6J mice. The mice were fed a cholesterol-enriched diet for five weeks to induce hypercholesterolemia and were then fed either the cholesterol-enriched diet or the cholesterol-enriched diet-supplemented formononetin or C7F for three weeks. Body weight and composition, glucose homeostasis......, and plasma lipids were compared. In another experiment, mice were fed the above diets for five weeks, and hepatic triglyceride accumulation and gene expression and histology of adipose tissue and liver were examined. Supplementation with C7F increased plasma HDL-cholesterol thereby increasing the plasma...

  15. Inactivation of basolateral amygdala prevents chronic immobilization stress-induced memory impairment and associated changes in corticosterone levels.

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    Tripathi, Sunil Jamuna; Chakraborty, Suwarna; Srikumar, B N; Raju, T R; Shankaranarayana Rao, B S

    2017-07-01

    Chronic stress causes detrimental effects on various forms of learning and memory. The basolateral amygdala (BLA) not only plays a crucial role in mediating certain forms of memory, but also in the modulation of the effects of stress. Chronic immobilization stress (CIS) results in hypertrophy of the BLA, which is believed to be one of the underlying causes for stress' effects on learning. Thus, it is plausible that preventing the effects of CIS on amygdala would preclude its deleterious cognitive effects. Accordingly, in the first part, we evaluated the effect of excitotoxic lesion of the BLA on chronic stress-induced hippocampal-dependent spatial learning using a partially baited radial arm maze task. The BLA was ablated bilaterally using ibotenic acid prior to CIS. Chronically stressed rats showed impairment in spatial learning with decreased percentage correct choice and increased reference memory errors. Excitotoxic lesion of the BLA prevented the impairment in spatial learning and reference memory. In the retention test, lesion of the BLA was able to rescue the chronic stress-induced impairment. Interestingly, stress-induced enhanced plasma corticosterone levels were partially prevented by the lesion of BLA. These results motivated us to evaluate if the same effects can be observed with temporary inactivation of BLA, only during stress. We found that chronic stress-induced spatial learning deficits were also prevented by temporary inactivation of the BLA. Additionally, temporary inactivation of BLA partially precluded the stress-induced increase in plasma corticosterone levels. Thus, inactivation of BLA precludes stress-induced spatial learning deficits, and enhanced plasma corticosterone levels. It is speculated that BLA inactivation-induced reduction in corticosterone levels during stress, might be crucial in restoring spatial learning impairments. Our study provides evidence that amygdalar modulation during stress might be beneficial for strategic

  16. FEL induced molecular operation on cultured fibroblast and cholesterol ester

    International Nuclear Information System (INIS)

    Awazu, Kunio; Ogino, Seiji; Nishimura, Eiichi; Tomimasu, Takio; Yasumoto, Masato.

    1997-01-01

    Free Electron Lasers can be used to molecular operation such as the delivery of a number of molecules into cells or the separation of cholesterol ester. First, cultured NIH3T3 cells are exposed to high-intensity short pulse Free Electron Laser (FEL). The FEL is tuned to an absorption maximum wavelength, 6.1 μm, which was measured by microscopic FTIR. A fluorescence dye in the cell suspension is more absorbed into the cell with the FEL exposure due to the FEL-induced mechanical stress to the cell membrane. A quantitative fluorescence microscopy is used to determine the efficiency of delivery. Second, as a compound in a lipid cell, cholesterol ester was exposed to 5.75 μm FEL. FTIR measurement was done to evaluate the modification of the cholesterol ester. The result showed that the fluorescence intensity of sample cells were higher than that of control cells, and there was significant difference between the control and the sample group. Blebbing and the colony formation of the cells were observed for cells with mechanical stress. As for the cholesterol ester, it can be modified by the FEL irradiation. These results showed that FEL can be used as a molecular operational tool by photo-chemical and photo-mechanical interaction. (author)

  17. Anthocyanin prevents CD40-activated proinflammatory signaling in endothelial cells by regulating cholesterol distribution.

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    Xia, Min; Ling, Wenhua; Zhu, Huilian; Wang, Qing; Ma, Jing; Hou, Mengjun; Tang, Zhihong; Li, Lan; Ye, Qinyuan

    2007-03-01

    Intracellular tumor necrosis factor receptor-associated factors (TRAFs) translocation to lipid rafts is a key element in CD40-induced signaling. The purpose of this study was to investigate the influence of anthocyanin on CD40-mediated proinflammatory events in human endothelial cells and the underlying possible molecular mechanism. Treatment of endothelial cells with anthocyanin prevented from CD40-induced proinflammatory status, measured by production of IL-6, IL-8, and monocyte chemoattractant protein-1 through inhibiting CD40-induced nuclear factor-kappaB (NF-kappaB) activation. TRAF-2 played pivotal role in CD40-NF-kappaB pathway as TRAF-2 small interference RNA (siRNA) diminished CD40-induced NF-kappaB activation and inflammation. TRAF-2 overexpression increased CD40-mediated NF-kappaB activation. Moreover, TRAF-2 almost totally recruited to lipid rafts after stimulation by CD40 ligand and depletion of cholesterol diminished CD40-mediated NF-kappaB activation. Exposure to anthocyanin not only interrupted TRAF-2 recruitment to lipid rafts but also decreased cholesterol content in Triton X-100 insoluble lipid rafts. However, anthocyanin did not influence the interaction between CD40 ligand and CD40 receptor. Our findings suggest that anthocyanin protects from CD40-induced proinflammatory signaling by preventing TRAF-2 translocation to lipid rafts through regulation of cholesterol distribution, which thereby may represent a mechanism that would explain the anti-inflammatory response of anthocyanin.

  18. Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats.

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    Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

    2015-04-01

    Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Air bubbles induce a critical continuous stress to prevent marine biofouling accumulation

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    Belden, Jesse; Menesses, Mark; Dickenson, Natasha; Bird, James

    2017-11-01

    Significant shear stresses are needed to remove established hard fouling organisms from a ship hull. Given that there is a link between the amount of time that fouling accumulates and the stress required to remove it, it is not surprising that more frequent grooming requires less shear stress. One approach to mitigate marine biofouling is to continuously introduce a curtain of air bubbles under a submerged surface; it is believed that this aeration exploits the small stresses induced by rising bubbles to continuously prevent accumulation. Although curtains of rising bubbles have successfully prevented biofouling accumulation, it is unclear if a single stream of bubbles could maintain a clean surface. In this talk, we show that single bubble stream aeration can prevent biofouling accumulation in regions for which the average wall stress exceeds approximately 0.01 Pa. This value is arrived at by comparing observations of biofouling growth and prevention from field studies with laboratory measurements that probe the associated flow fields. We also relate the spatial and temporal characteristics of the flow to the size and frequency of the rising bubbles, which informs the basic operating conditions required for aeration to continuously prevent biofouling accumulation.

  20. Topical cholesterol in clofazimine induced ichthyosis

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    Pandey S

    1994-01-01

    Full Text Available Topical application of 10% cholesterol in petrolatum significantly (P< 0.05 controlled the development of ichthyosis in 62 patients taking 100 mg clofazimine daily for a period of 3 months. However, topical cholesterol application did not affect the lowering of serum cholesterol induced by oral clofazimine. Probable mechanism of action is being discussed.

  1. N-acetylcysteine prevents stress-induced anxiety behavior in zebrafish.

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    Mocelin, Ricieri; Herrmann, Ana P; Marcon, Matheus; Rambo, Cassiano L; Rohden, Aline; Bevilaqua, Fernanda; de Abreu, Murilo Sander; Zanatta, Leila; Elisabetsky, Elaine; Barcellos, Leonardo J G; Lara, Diogo R; Piato, Angelo L

    2015-12-01

    Despite the recent advances in understanding the pathophysiology of anxiety disorders, the pharmacological treatments currently available are limited in efficacy and induce serious side effects. A possible strategy to achieve clinical benefits is drug repurposing, i.e., discovery of novel applications for old drugs, bringing new treatment options to the market and to the patients who need them. N-acetylcysteine (NAC), a commonly used mucolytic and paracetamol antidote, has emerged as a promising molecule for the treatment of several neuropsychiatric disorders. The mechanism of action of this drug is complex, and involves modulation of antioxidant, inflammatory, neurotrophic and glutamate pathways. Here we evaluated the effects of NAC on behavioral parameters relevant to anxiety in zebrafish. NAC did not alter behavioral parameters in the novel tank test, prevented the anxiety-like behaviors induced by an acute stressor (net chasing), and increased the time zebrafish spent in the lit side in the light/dark test. These data may indicate that NAC presents an anti-stress effect, with the potential to prevent stress-induced psychiatric disorders such as anxiety and depression. The considerable homology between mammalian and zebrafish genomes invests the current data with translational validity for the further clinical trials needed to substantiate the use of NAC in anxiety disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats.

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    Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Alam, Md Ashraful

    2015-01-01

    We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis.

  3. Activating transcription factor 6 mediates oxidized LDL-induced cholesterol accumulation and apoptosis in macrophages by up-regulating CHOP expression.

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    Yao, Shutong; Zong, Chuanlong; Zhang, Ying; Sang, Hui; Yang, Mingfeng; Jiao, Peng; Fang, Yongqi; Yang, Nana; Song, Guohua; Qin, Shucun

    2013-01-01

    This study was to explore whether activating transcription factor 6 (ATF6), an important sensor to endoplasmic reticulum (ER) stress, would mediate oxidized low-density lipoprotein (ox-LDL)- induced cholesterol accumulation and apoptosis in cultured macrophages and the underlying molecular mechanisms. Intracellular lipid droplets and total cholesterol levels were assayed by oil red O staining and enzymatic colorimetry, respectively. Cell viability and apoptosis were determined using MTT assay and AnnexinV-FITC apoptosis detection kit, respectively. The nuclear translocation of ATF6 in cells was detected by immunofluorescence analysis. Protein and mRNA levels were examined by Western blot analysis and real time-PCR, respectively. ATF6 siRNA was transfected to RAW264.7 cells by lipofectamin. Exposure of cells to ox-LDL induced glucose-regulated protein 78 (GRP78). C/EBP homologous protein (CHOP), a key-signaling component of ER stress-induced apoptosis, was up-regulated in ox-LDL-treated cells. ATF6, a factor that positively regulates CHOP expression, was activated by ox-LDL in a concentration- and time- dependent manner. The role of the ATF6-mediated ER stress pathway was further confirmed through the siRNA-mediated knockdown of ATF6, which attenuated ox-LDL-induced upregulation of CHOP, cholesterol accumulation and apoptosis in macrophages. In addition, the phosphorylation of double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK), another factor that positively regulates CHOP expression, was induced in the presence of ox-LDL, and PERK-specific siRNA also inhibited the ox-LDL-induced upregulation of CHOP and apoptosis in RAW264.7 cells. These results demonstrate that ER stress-related proteins, particularly ATF6 and its downstream molecule CHOP, are involved in ox-LDL-induced cholesterol accumulation and apoptosis in macrophages.

  4. Role of Cardamom (Elettaria cardamomum) in Ameliorating Radiation Induced Oxidative Stress In Rats

    International Nuclear Information System (INIS)

    Darwish, M.M.; Abd El Azime, A. Sh.

    2013-01-01

    Radiation is one of the most widespread sources of environmental stress in living environment which cause oxidative stress and metabolic changes. The present study aims to evaluate the antioxidant effect of Cardamom (Elettaria cardamomum) on gamma radiation-induced oxidative damage in liver and heart tis sues. The study was conducted on forty (40) rats which were classified into four equal groups. Group1: Control group, Group. 2: rats given cardamom in basal diet.Group3: Irradiated rats, rats were subjected to whole body gamma irradiation at 6 Gy delivere d as single exposure dose. Group 4: irradiated +cardamom: rats receiving cardamom for 4 weeks and irradiated. The animals were scarified 24h after irradiation. Irradiated animals had significant increase in oxidative stress markers in liver and heart tissues expressed by significant increase of malondialdehyde (MDA) content associated to significant depletion of superoxide dismutase (SOD) , catalase (CAT) activities, and reduced glutathione (GSH) content . Hepatic and cardiac changes included significant increases of serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) , total cholesterol(TC), triacylglycerol(TAG), low-density lipoprotein cholesterol(LDL-C), and iron concentration. While, a significant decre ase in high-density lipoprotein-cholesterol (HDL-C), manganese and copper were observed. Addition of cardamom to the basal diet prior to gamma radiation, improved the tested parameters . So it is a therapeutic alternative for oxidative stress, hyperlipidaemia and trace elements changes. . The data obtained in this study suggest that cardamom may prevent liver and heart from radiation-induced damage.

  5. Novel oxindole derivatives prevent oxidative stress-induced cell death in mouse hippocampal HT22 cells.

    Science.gov (United States)

    Hirata, Yoko; Yamada, Chika; Ito, Yuki; Yamamoto, Shotaro; Nagase, Haruna; Oh-Hashi, Kentaro; Kiuchi, Kazutoshi; Suzuki, Hiromi; Sawada, Makoto; Furuta, Kyoji

    2018-03-15

    The current medical and surgical therapies for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease offer symptomatic relief but do not provide a cure. Thus, small synthetic compounds that protect neuronal cells from degeneration are critically needed to prevent and treat these. Oxidative stress has been implicated in various pathophysiological conditions, including neurodegenerative diseases. In a search for neuroprotective agents against oxidative stress using the murine hippocampal HT22 cell line, we found a novel oxindole compound, GIF-0726-r, which prevented oxidative stress-induced cell death, including glutamate-induced oxytosis and erastin-induced ferroptosis. This compound also exerted a protective effect on tunicamycin-induced ER stress to a lesser extent but had no effect on campthothecin-, etoposide- or staurosporine-induced apoptosis. In addition, GIF-0726-r was also found to be effective after the occurrence of oxidative stress. GIF-0726-r was capable of inhibiting reactive oxygen species accumulation and Ca 2+ influx, a presumed executor in cell death, and was capable of activating the antioxidant response element, which is a cis-acting regulatory element in promoter regions of several genes encoding phase II detoxification enzymes and antioxidant proteins. These results suggest that GIF-0726-r is a low-molecular-weight compound that prevents neuronal cell death through attenuation of oxidative stress. Among the more than 200 derivatives of the GIF-0726-r synthesized, we identified the 11 most potent activators of the antioxidant response element and characterized their neuroprotective activity in HT22 cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. GRP94 Regulates Circulating Cholesterol Levels through Blockade of PCSK9-Induced LDLR Degradation

    Directory of Open Access Journals (Sweden)

    Steve Poirier

    2015-12-01

    Full Text Available Clearance of circulating low-density lipoprotein cholesterol (LDLc by hepatic LDL receptors (LDLR is central for vascular health. Secreted by hepatocytes, PCSK9 induces the degradation of LDLR, resulting in higher plasma LDLc levels. Still, it remains unknown why LDLR and PCSK9 co-exist within the secretory pathway of hepatocytes without leading to complete degradation of LDLR. Herein, we identified the ER-resident GRP94, and more precisely its client-binding C-terminal domain, as a PCSK9-LDLR inhibitory binding protein. Depletion of GRP94 did not affect calcium homeostasis, induce ER stress, nor did it alter PCSK9 processing or its secretion but greatly increased its capacity to induce LDLR degradation. Accordingly, we found that hepatocyte-specific Grp94-deficient mice have higher plasma LDLc levels correlated with ∼80% reduction in hepatic LDLR protein levels. Thus, we provide evidence that, in physiological conditions, binding of PCSK9 to GRP94 protects LDLR from degradation likely by preventing early binding of PCSK9 to LDLR within the ER.

  7. Gallic acid prevents nonsteroidal anti-inflammatory drug-induced gastropathy in rat by blocking oxidative stress and apoptosis.

    Science.gov (United States)

    Pal, Chinmay; Bindu, Samik; Dey, Sumanta; Alam, Athar; Goyal, Manish; Iqbal, Mohd Shameel; Maity, Pallab; Adhikari, Susanta S; Bandyopadhyay, Uday

    2010-07-15

    Nonsteroidal anti-inflammatory drug (NSAID)-induced oxidative stress plays a critical role in gastric mucosal cell apoptosis and gastropathy. NSAIDs induce the generation of hydroxyl radical ((*)OH) through the release of free iron, which plays an important role in developing gastropathy. Thus, molecules having both iron-chelating and antiapoptotic properties will be beneficial in preventing NSAID-induced gastropathy. Gallic acid (GA), a polyphenolic natural product, has the capacity to chelate free iron. Here, we report that GA significantly prevents, as well as heals, NSAID-induced gastropathy. In vivo, GA blocks NSAID-mediated mitochondrial oxidative stress by preventing mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. In vitro, GA scavenges free radicals and blocks (*)OH-mediated oxidative damage. GA also attenuates gastric mucosal cell apoptosis in vivo as well as in vitro in cultured gastric mucosal cells as evident from the TUNEL assay. GA prevents NSAID-induced activation of caspase-9, a marker for the mitochondrial pathway of apoptosis, and restores NSAID-mediated collapse of the mitochondrial transmembrane potential and dehydrogenase activity. Thus, the inhibition of mitochondrial oxidative stress by GA is associated with the inhibition of NSAID-induced mitochondrial dysfunction and activation of apoptosis in gastric mucosal cells, which are responsible for gastric injury or gastropathy. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Estrogen receptor-a in the medial amygdala prevents stress-induced elevations in blood pressure in females

    Science.gov (United States)

    Psychological stress contributes to the development of hypertension in humans. The ovarian hormone, estrogen, has been shown to prevent stress-induced pressor responses in females by unknown mechanisms. Here, we showed that the antihypertensive effects of estrogen during stress were blunted in femal...

  9. Preventive effect of theanine intake on stress-induced impairments of hippocamapal long-term potentiation and recognition memory.

    Science.gov (United States)

    Tamano, Haruna; Fukura, Kotaro; Suzuki, Miki; Sakamoto, Kazuhiro; Yokogoshi, Hidehiko; Takeda, Atsushi

    2013-06-01

    Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. On the basis of the preventive effect of theanine intake after birth on mild stress-induced attenuation of hippocamapal CA1 long-term potentiation (LTP), the present study evaluated the effect of theanine intake after weaning on stress-induced impairments of LTP and recognition memory. Young rats were fed water containing 0.3% theanine for 3 weeks after weaning and subjected to water immersion stress for 30min, which was more severe than tail suspension stress for 30s used previously. Serum corticosterone levels were lower in theanine-administered rats than in the control rats even after exposure to stress. CA1 LTP induced by a 100-Hz tetanus for 1s was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an N-methyl-d-aspartate (NMDA) receptor antagonist, in hippocampal slices from the control rats and was attenuated by water immersion stress. In contrast, CA1 LTP was not significantly inhibited in the presence of APV in hippocampal slices from theanine-administered rats and was not attenuated by the stress. Furthermore, object recognition memory was impaired in the control rats, but not in theanine-administered rats. The present study indicates the preventive effect of theanine intake after weaning on stress-induced impairments of hippocampal LTP and recognition memory. It is likely that the modification of corticosterone secretion after theanine intake is involved in the preventive effect. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. 2H NMR evidence for antibiotic-induced cholesterol immobilization in biological model membranes

    International Nuclear Information System (INIS)

    Dufourc, E.J.; Smith, I.C.

    1985-01-01

    The interaction of the polyene antibiotic filipin with membrane sterols has been studied by deuterium nuclear magnetic resonance of the molecular probes [2,2,3,4,4,6- 2 H6]cholesterol and 1-myristoyl-2-[4',4',14',14',14'- 2 H5]myristoyl-sn-glycero-3-phospho- choline. At physiological temperatures, there is evidence of filipin-induced cholesterol immobilization in the membrane. The 2 H NMR spectra of cholesterol show two domains in which ordering and dynamics are very different. In one of these, cholesterol is static on the 2 H NMR time scale, whereas in the other it undergoes rapid axially symmetric motions similar to those it exhibits in the drug-free membrane; this indicates that the jumping frequency of cholesterol between the labile and immobilized domains is less than 10(5) s -1 . The distribution of cholesterol between these two sites is temperature dependent. In contrast to cholesterol, the phospholipids sense only one type of environment, at both the top and center of the bilayer, indicating that cholesterol acts as a screen, preventing the lipids from direct interaction with the antibiotic. At low temperature, the ordering of the lipid in the presence of cholesterol does not change upon filipin addition, whereas at elevated temperatures the local ordering of both the lipid and the labile cholesterol is significantly lower than that in the absence of the drug

  11. Protective potentials of wild rice (Zizania latifolia (Griseb) Turcz) against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats.

    Science.gov (United States)

    Han, Shu-Fen; Zhang, Hong; Zhai, Cheng-Kai

    2012-07-01

    The study evaluates the protective potentials of wild rice against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats. In addition to the rats of low-fat diet group, others animals were exposed to a high-fat/cholesterol diet condition for 8 weeks. The city diet (CD) is based on the diet consumed by urban residents in modern China, which is rich in fat/cholesterol and high in carbohydrates from white rice and processed wheat starch. The chief source of dietary carbohydrates of wild rice diet (WRD) is from Chinese wild rice and other compositions are the same with CD. Rats fed CD showed elevated body and liver organ weights, lipid profiles, free fatty acids (FFA) and leptin comparable with rats fed high-fat/cholesterol diet (HFD) known to induce obesity and hyperlipidaemia in this species. However, rats consuming WRD suppressed the increase of lipid droplets accumulation, FFA, and leptin, and the decrease of lipoprotein lipase and adipose triglyceride lipase. Meanwhile, WRD prevented high-fat/cholesterol diet-induced elevation in protein expression of sterol-regulatory element binding protein-1c, and gene expression of fatty acid synthase and acetyl-CoA carboxylase. These findings indicate that wild rice as a natural food has the potentials of preventing obesity and liver lipotoxicity induced by a high-fat/cholesterol diet in rats. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Effects of Selenium Yeast on Blood Glucose and Antioxidant Biomarkers in Cholesterol Fed Diet Induced Type 2 Diabetes Mellitus in Wistar Rats.

    Science.gov (United States)

    Tanko, Y; Jimoh, A; Ahmed, A; Adam, A; Ejeh, L; Mohammed, A; Ayo, J O

    2017-03-06

    Selenium is an antioxidant that prevents oxygen radical from damaging cells from chronic diseases that can develop from cell injury and inflammation such as diabetes mellitus. The aim of the study is to investigate the possible protective effect of selenium yeast on cholesterol diet induced type-2 diabetes mellitus and oxidative stress in rats. Twenty male wistar rats were divided in to four groups of five animals each: Group 1: (Negative control) received standard animal feed only, Group 2:  received cholesterol diet (CD) only, Group 3: received CD and 0.1 mg/kg selenium yeast orally, Group 4: Received CD and 0.2 mg/kg selenium yeast orally for six weeks. At the end of the study period, the animals were sacrificed and the serum samples were collected and evaluated for estimation of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). The results showed a significant decrease in blood glucose level in the groups  co-administered CD and selenium yeast when compared to CD group only. Antioxidant enzymes status recorded significant decrease in SOD, CAT and GPx activities in CD and selenium yeast administered when compared to CD group only. In Conclusion, Selenium yeast administrations prevent free radical formations which are potent inducer of diabetes mellitus.

  13. Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans.

    Science.gov (United States)

    Ihara, Akiko; Uno, Masaharu; Miyatake, Koichi; Honjoh, Sakiko; Nishida, Eisuke

    2017-01-01

    Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Inhibition of a Descending Prefrontal Circuit Prevents Ketamine-Induced Stress Resilience in Females

    DEFF Research Database (Denmark)

    Dolzani, S. D.; Baratta, M. V.; Moss, J. M.

    2018-01-01

    . The NMDA receptor antagonist ketamine has recently emerged as a prophylactic capable of preventing neurochemical and behavioral outcomes of a future stressor. Despite promising results of preclinical studies performed in male rats, the effects of proactive ketamine in female rats remains unknown....... This is alarming given that stress-related disorders affect females at nearly twice the rate of males. Here we explore the prophylactic effects of ketamine on stress-induced anxiety-like behavior and the neural circuit-level processes that mediate these effects in female rats. Ketamine given one week prior...... to an uncontrollable stressor (inescapable tailshock; IS) reduced typical stress-induced activation of the serotonergic (5-HT) dorsal raphe nucleus (DRN) and eliminated DRN-dependent juvenile social exploration (JSE) deficits 24 h after the stressor. Proactive ketamine altered prelimbic cortex (PL) neural ensembles so...

  15. Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet.

    Science.gov (United States)

    Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A

    2013-01-15

    Caffeine alleviates cognitive impairment associated with a variety of health conditions. In this study, we examined the effect of caffeine treatment on chronic stress- and/or high fat-high carbohydrate Western diet (WD)-induced impairment of learning and memory in rats. Chronic psychosocial stress, WD and caffeine (0.3 g/L in drinking water) were simultaneously administered for 3 months to adult male Wistar rats. At the conclusion of the 3 months, and while the previous treatments continued, rats were tested in the radial arm water maze (RAWM) for learning, short-term and long-term memory. This procedure was applied on a daily basis to all animals for 5 consecutive days or until the animal reaches days to criterion (DTC) in the 12th learning trial and memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Chronic stress and/or WD groups caused impaired learning, which was prevented by chronic caffeine administration. In the memory tests, chronic caffeine administration also prevented memory impairment during chronic stress conditions and/or WD. Furthermore, DTC value for caffeine treated stress, WD, and stress/WD groups indicated that caffeine normalizes memory impairment in these groups. These results showed that chronic caffeine administration prevented stress and/or WD-induced impairment of spatial learning and memory. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation.

    Science.gov (United States)

    Dang, Eric V; McDonald, Jeffrey G; Russell, David W; Cyster, Jason G

    2017-11-16

    Type I interferon restrains interleukin-1β (IL-1β)-driven inflammation in macrophages by upregulating cholesterol-25-hydroxylase (Ch25h) and repressing SREBP transcription factors. However, the molecular links between lipid metabolism and IL-1β production remain obscure. Here, we demonstrate that production of 25-hydroxycholesterol (25-HC) by macrophages is required to prevent inflammasome activation by the DNA sensor protein absent in melanoma 2 (AIM2). We find that in response to bacterial infection or lipopolysaccharide (LPS) stimulation, macrophages upregulate Ch25h to maintain repression of SREBP2 activation and cholesterol synthesis. Increasing macrophage cholesterol content is sufficient to trigger IL-1β release in a crystal-independent but AIM2-dependent manner. Ch25h deficiency results in cholesterol-dependent reduced mitochondrial respiratory capacity and release of mitochondrial DNA into the cytosol. AIM2 deficiency rescues the increased inflammasome activity observed in Ch25h -/- . Therefore, activated macrophages utilize 25-HC in an anti-inflammatory circuit that maintains mitochondrial integrity and prevents spurious AIM2 inflammasome activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Chitosan Prevents Gentamicin-Induced Nephrotoxicity via a Carbonyl Stress-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Chu-Kung Chou

    2015-01-01

    Full Text Available Aminoglycosides are widely used to treat infections; however, their applications are limited by nephrotoxicity. With the increase of antibiotic resistance, the use of aminoglycosides is inevitable. Low-molecular-weight chitosan (LMWC has shown renal protective effects in dialysis patients. However, no study has evaluated LMWC for preventing aminoglycoside-induced nephrotoxicity or determined the mechanisms underlying the renal protective effects. In this study, LMWC (165 or 825 mg/kg/day or metformin (100 mg/kg/day was orally administered for 13 days to rats with nephropathy induced by gentamicin (GM, a kind of aminoglycoside (150 mg/kg/day i.p. for 6 days. Both LMCW doses improved renal function. Serum creatinine levels improved in rats treated with 165 and 825 mg/kg/day LMWC (from 2.14 ± 0.74 mg/dL to 1.26 ± 0.46 mg/dL and 0.69 ± 0.12 mg/dL, resp., P < 0.05. Blood urea nitrogen levels were also improved in these rats (from 73.73 ± 21.13 mg/dL to 58.70 ± 22.71 mg/dL and 28.82 ± 3.84 mg/dL, resp., P < 0.05. Additionally, renal tissue morphology improved after LMWC treatment, and accumulation of renal methylglyoxal, a damage factor associated with carbonyl stress, was reversed. These results show that LMWC prevents GM-induced renal toxicity via a carbonyl stress-dependent pathway.

  18. The Drosophila carbonyl reductase sniffer prevents oxidative stress-induced neurodegeneration.

    Science.gov (United States)

    Botella, Jose A; Ulschmid, Julia K; Gruenewald, Christoph; Moehle, Christoph; Kretzschmar, Doris; Becker, Katja; Schneuwly, Stephan

    2004-05-04

    A growing body of evidence suggests that oxidative stress is a common underlying mechanism in the pathogenesis of neurodegenerative disorders such as Alzheimer's, Huntington's, Creutzfeld-Jakob and Parkinson's diseases. Despite the increasing number of reports finding a causal relation between oxidative stress and neurodegeneration, little is known about the genetic elements that confer protection against the deleterious effects of oxidation in neurons. We have isolated and characterized the Drosophila melanogaster gene sniffer, whose function is essential for preventing age-related neurodegeneration. In addition, we demonstrate that oxidative stress is a direct cause of neurodegeneration in the Drosophila central nervous system and that reduction of sniffer activity leads to neuronal cell death. The overexpression of the gene confers neuronal protection against oxygen-induced apoptosis, increases resistance of flies to experimental normobaric hyperoxia, and improves general locomotor fitness. Sniffer belongs to the family of short-chain dehydrogenase/reductase (SDR) enzymes and exhibits carbonyl reductase activity. This is the first in vivo evidence of the direct and important implication of this enzyme as a neuroprotective agent in the cellular defense mechanisms against oxidative stress.

  19. Euterpe oleracea Mart.-Derived Polyphenols Protect Mice from Diet-Induced Obesity and Fatty Liver by Regulating Hepatic Lipogenesis and Cholesterol Excretion.

    Science.gov (United States)

    de Oliveira, Paola Raquel B; da Costa, Cristiane A; de Bem, Graziele F; Cordeiro, Viviane S C; Santos, Izabelle B; de Carvalho, Lenize C R M; da Conceição, Ellen Paula S; Lisboa, Patrícia Cristina; Ognibene, Dayane T; Sousa, Pergentino José C; Martins, Gabriel R; da Silva, Antônio Jorge R; de Moura, Roberto S; Resende, Angela C

    2015-01-01

    The aim of this study was to investigate the effect of a polyphenol-rich Açaí seed extract (ASE, 300 mg/kg-1d-1) on adiposity and hepatic steatosis in mice that were fed a high-fat (HF) diet and its underlying mechanisms based on hepatic lipid metabolism and oxidative stress. Four groups were studied: C57BL/6 mice that were fed with standard diet (10% fat, Control), 10% fat + ASE (ASE), 60% fat (HF), and 60% fat + ASE (HF + ASE) for 12 weeks. We evaluated the food intake, body weight gain, serum glucose and lipid profile, hepatic cholesterol and triacyglycerol (TG), hepatic expression of pAMPK, lipogenic proteins (SREBP-1c, pACC, ACC, HMG-CoA reductase) and cholesterol excretion transporters, ABCG5 and ABCG8. We also evaluated the steatosis in liver sections and oxidative stress. ASE reduced body weight gain, food intake, glucose levels, accumulation of cholesterol and TG in the liver, which was associated with a reduction of hepatic steatosis. The increased expressions of SREBP-1c and HMG-CoA reductase and reduced expressions of pAMPK and pACC/ACC in HF group were antagonized by ASE. The ABCG5 and ABCG8 transporters expressions were increased by the extract. The antioxidant effect of ASE was demonstrated in liver of HF mice by restoration of SOD, CAT and GPx activities and reduction of the increased levels of malondialdehyde and protein carbonylation. In conclusion, ASE substantially reduced the obesity and hepatic steatosis induced by HF diet by reducing lipogenesis, increasing cholesterol excretion and improving oxidative stress in the liver, providing a nutritional resource for prevention of obesity-related adiposity and hepatic steatosis.

  20. The triterpenoids of Ganoderma tsugae prevent stress-induced myocardial injury in mice.

    Science.gov (United States)

    Kuok, Qian-Yu; Yeh, Chen-Yu; Su, Bor-Chyuan; Hsu, Pei-Ling; Ni, Hao; Liu, Ming-Yie; Mo, Fan-E

    2013-10-01

    Ganoderma mushrooms (Lingzhi in Chinese) have well-documented health benefits. Ganoderma tsugae (G. tsugae), one of the ganoderma species, has been commercially cultivated as a dietary supplement. Because G. tsugae has high antioxidant activity and because oxidative stress is often associated with cardiac injury, we hypothesized that G. tsugae protects against cardiac injury by alleviating oxidative stress. We tested the hypothesis using a work-overload-induced myocardial injury model created by challenging mice with isoproterenol (ISO). Remarkably, oral G. tsugae protected the mice from ISO-induced myocardial injury. Moreover, the triterpenoid fraction of G. tsugae, composed of a mixture of nine structurally related ganoderic acids (GAs), provided cardioprotection by inhibiting the ISO-induced expression of Fas/Fas ligand, oxidative stress, and apoptosis. The antioxidant activity of GAs was tested in cultured cardio-myoblast H9c2 cells against the insult of H₂O₂. GAs dissipated the cellular reactive oxygen species imposed by H₂O₂ and prevented cell death. Our findings uncovered the cardioprotective activity of G. tsugae and identified GAs as the bioactive components against cardiac insults. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Stroke survivors' endorsement of a "stress belief model" of stroke prevention predicts control of risk factors for recurrent stroke.

    Science.gov (United States)

    Phillips, L Alison; Tuhrim, Stanley; Kronish, Ian M; Horowitz, Carol R

    2014-01-01

    Perceptions that stress causes and stress-reduction controls hypertension have been associated with poorer blood pressure (BP) control in hypertension populations. The current study investigated these "stress-model perceptions" in stroke survivors regarding prevention of recurrent stroke and the influence of these perceptions on patients' stroke risk factor control. Stroke and transient ischemic attack survivors (N=600) participated in an in-person interview in which they were asked about their beliefs regarding control of future stroke; BP and cholesterol were measured directly after the interview. Counter to expectations, patients who endorsed a "stress-model" but not a "medication-model" of stroke prevention were in better control of their stroke risk factors (BP and cholesterol) than those who endorsed a medication-model but not a stress-model of stroke prevention (OR for poor control=.54, Wald statistic=6.07, p=.01). This result was not explained by between group differences in patients' reported medication adherence. The results have implications for theory and practice, regarding the role of stress belief models and acute cardiac events, compared to chronic hypertension.

  2. Rho kinase inhibitor fasudil mitigates high-cholesterol diet-induced hypercholesterolemia and vascular damage.

    Science.gov (United States)

    Abdali, Nibrass Taher; Yaseen, Awny H; Said, Eman; Ibrahim, Tarek M

    2017-04-01

    The current study was designed to investigate the potential beneficial therapeutic outcome of Rho kinase inhibitor (fasudil) against hypercholesterolemia-induced myocardial and vascular injury in rabbits together with diet modification. Sixteen male rabbits were randomly divided into four groups: normal control group which received standard rabbit chow, hypercholesterolemic control group, and treated groups which received cholesterol-rich rabbit chow (1.5% cholesterol) for 8 weeks. Treated groups received either fasudil (100 mg/kg/day) or rosuvastatin (2.5 mg/kg/day) starting from the ninth week for further 4 weeks with interruption of the cholesterol-rich chow. Biochemical assessment of serum cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and myocardial oxidative/antioxidant biomarkers malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), besides biochemical assessment of serum nitric oxide (NO), creatine kinase (CK), and lactate dehydrogenase (LDH) activities and serum total antioxidant capacity (TAC), was conducted. Serum vascular cell adhesion molecule 1 (VCAM-1) and serum Rho-associated protein kinase 1 (ROCK-1) were also evaluated along with histopathological examination of aorta specimens. Fasudil administration significantly decreased serum cholesterol, triglyceride (TG), and LDL and significantly increased serum HDL, with concomitant decrease in serum CK and LDH activities, NO, and restoration of serum TAC. Myocardial MDA significantly declined; SOD activity and GSH contents were restored. Serum ROCK-1 and VCAM-1 levels significantly declined as well. Vascular improvement was confirmed with histopathological examination, which revealed normal aortic intema with the absence of atheromas. Fasudil has promising anti-atherogenic activity mediated primarily via alleviation of hypercholesterolemia-induced oxidative stress and modulation of inflammatory response.

  3. Blueberry polyphenols prevent cardiomyocyte death by preventing calpain activation and oxidative stress.

    Science.gov (United States)

    Louis, Xavier Lieben; Thandapilly, Sijo Joseph; Kalt, Wilhelmina; Vinqvist-Tymchuk, Melinda; Aloud, Basma Milad; Raj, Pema; Yu, Liping; Le, Hoa; Netticadan, Thomas

    2014-08-01

    The purpose of this study was to examine the efficacy of an aqueous wild blueberry extract and five wild blueberry polyphenol fractions on an in vitro model of heart disease. Adult rat cardiomyocytes were pretreated with extract and fractions, and then exposed to norepinephrine (NE). Cardiomyocyte hypertrophy, cell death, oxidative stress, apoptosis and cardiomyocyte contractile function as well as the activities of calpain, superoxide dismutase (SOD) and catalase (CAT) were measured in cardiomyocytes treated with and without NE and blueberry fraction (BF). Four of five blueberry fractions prevented cell death and cardiomyocyte hypertrophy induced by NE. Total phenolic fraction was used for all further analysis. The NE-induced increase in oxidative stress, nuclear condensation, calpain activity and lowering of SOD and CAT activities were prevented upon pretreatment with BF. Reduced contractile function was also significantly improved with BF pretreatment. Blueberry polyphenols prevent NE-induced adult cardiomyocyte hypertrophy and cell death. The protective effects of BF may be in part attributed to a reduction in calpain activity and oxidative stress.

  4. Mineralocorticoid receptor blockade prevents stress-induced modulation of multiple memory systems in the human brain.

    Science.gov (United States)

    Schwabe, Lars; Tegenthoff, Martin; Höffken, Oliver; Wolf, Oliver T

    2013-12-01

    Accumulating evidence suggests that stress may orchestrate the engagement of multiple memory systems in the brain. In particular, stress is thought to favor dorsal striatum-dependent procedural over hippocampus-dependent declarative memory. However, the neuroendocrine mechanisms underlying these modulatory effects of stress remain elusive, especially in humans. Here, we targeted the role of the mineralocorticoid receptor (MR) in the stress-induced modulation of dorsal striatal and hippocampal memory systems in the human brain using a combination of event-related functional magnetic resonance imaging and pharmacologic blockade of the MR. Eighty healthy participants received the MR antagonist spironolactone (300 mg) or a placebo and underwent a stressor or control manipulation before they performed, in the scanner, a classification task that can be supported by the hippocampus and the dorsal striatum. Stress after placebo did not affect learning performance but reduced explicit task knowledge and led to a relative increase in the use of more procedural learning strategies. At the neural level, stress promoted striatum-based learning at the expense of hippocampus-based learning. Functional connectivity analyses showed that this shift was associated with altered coupling of the amygdala with the hippocampus and dorsal striatum. Mineralocorticoid receptor blockade before stress prevented the stress-induced shift toward dorsal striatal procedural learning, same as the stress-induced alterations of amygdala connectivity with hippocampus and dorsal striatum, but resulted in significantly impaired performance. Our findings indicate that the stress-induced shift from hippocampal to dorsal striatal memory systems is mediated by the amygdala, required to preserve performance after stress, and dependent on the MR. © 2013 Society of Biological Psychiatry.

  5. Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels.

    Science.gov (United States)

    Vignisse, Julie; Sambon, Margaux; Gorlova, Anna; Pavlov, Dmitrii; Caron, Nicolas; Malgrange, Brigitte; Shevtsova, Elena; Svistunov, Andrey; Anthony, Daniel C; Markova, Natalyia; Bazhenova, Natalyia; Coumans, Bernard; Lakaye, Bernard; Wins, Pierre; Strekalova, Tatyana; Bettendorff, Lucien

    2017-07-01

    Thiamine is essential for normal brain function and its deficiency causes metabolic impairment, specific lesions, oxidative damage and reduced adult hippocampal neurogenesis (AHN). Thiamine precursors with increased bioavailability, especially benfotiamine, exert neuroprotective effects not only for thiamine deficiency (TD), but also in mouse models of neurodegeneration. As it is known that AHN is impaired by stress in rodents, we exposed C57BL6/J mice to predator stress for 5 consecutive nights and studied the proliferation (number of Ki67-positive cells) and survival (number of BrdU-positive cells) of newborn immature neurons in the subgranular zone of the dentate gyrus. In stressed mice, the number of Ki67- and BrdU-positive cells was reduced compared to non-stressed animals. This reduction was prevented when the mice were treated (200mg/kg/day in drinking water for 20days) with thiamine or benfotiamine, that were recently found to prevent stress-induced behavioral changes and glycogen synthase kinase-3β (GSK-3β) upregulation in the CNS. Moreover, we show that thiamine and benfotiamine counteract stress-induced bodyweight loss and suppress stress-induced anxiety-like behavior. Both treatments induced a modest increase in the brain content of free thiamine while the level of thiamine diphosphate (ThDP) remained unchanged, suggesting that the beneficial effects observed are not linked to the role of this coenzyme in energy metabolism. Predator stress increased hippocampal protein carbonylation, an indicator of oxidative stress. This effect was antagonized by both thiamine and benfotiamine. Moreover, using cultured mouse neuroblastoma cells, we show that in particular benfotiamine protects against paraquat-induced oxidative stress. We therefore hypothesize that thiamine compounds may act by boosting anti-oxidant cellular defenses, by a mechanism that still remains to be unveiled. Our study demonstrates, for the first time, that thiamine and benfotiamine prevent

  6. MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content

    Directory of Open Access Journals (Sweden)

    Elisa Balboa

    2017-08-01

    Full Text Available MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1. However, the role of MLN64 in the maintenance of endosomal cholesterol flow and intracellular cholesterol homeostasis remains unclear. We have previously described that hepatic MLN64 overexpression increases liver cholesterol content and induces liver damage. Here, we studied the function of MLN64 in normal and NPC1-deficient cells and we evaluated whether MLN64 overexpressing cells exhibit alterations in mitochondrial function. We used recombinant-adenovirus-mediated MLN64 gene transfer to overexpress MLN64 in mouse liver and hepatic cells; and RNA interference to down-regulate MLN64 in NPC1-deficient cells. In MLN64-overexpressing cells, we found increased mitochondrial cholesterol content and decreased glutathione (GSH levels and ATPase activity. Furthermore, we found decreased mitochondrial membrane potential and mitochondrial fragmentation and increased mitochondrial superoxide levels in MLN64-overexpressing cells and in NPC1-deficient cells. Consequently, MLN64 expression was increased in NPC1-deficient cells and reduction of its expression restore mitochondrial membrane potential and mitochondrial superoxide levels. Our findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, we demonstrate that MLN64 expression is increased in NPC cells and plays a key role in cholesterol transport into the mitochondria.

  7. Andrographolide Inhibits Oxidized LDL-Induced Cholesterol Accumulation and Foam Cell Formation in Macrophages.

    Science.gov (United States)

    Lin, Hung-Chih; Lii, Chong-Kuei; Chen, Hui-Chun; Lin, Ai-Hsuan; Yang, Ya-Chen; Chen, Haw-Wen

    2018-01-01

    oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells. Transcription factor liver X receptor [Formula: see text] (LXR[Formula: see text] plays a key role in lipid metabolism and inflammation as well as in the regulation of ABCA1 and ABCG1 expression. Because of the contribution of inflammation to macrophage foam cell formation and the potent anti-inflammatory activity of andrographolide, we hypothesized that andrographolide might inhibit oxLDL-induced macrophage foam cell formation. The results showed that andrographolide reduced oxLDL-induced lipid accumulation in macrophage foam cells. Andrographolide decreased the mRNA and protein expression of CD36 by inducing the degradation of CD36 mRNA; however, andrographolide had no effect on SR-A expression. In contrast, andrographolide increased the mRNA and protein expression of ABCA1 and ABCG1, which were dependent on LXR[Formula: see text]. Andrographolide enhanced LXR[Formula: see text] nuclear translocation and DNA binding activity. Treatment with the LXR[Formula: see text] antagonist GGPP and transfection with LXR[Formula: see text] siRNA reversed the ability of andrographolide to stimulate ABCA1 and ABCG1 protein expression. In conclusion, inhibition of CD36-mediated oxLDL uptake and induction of ABCA1- and ABCG1-dependent cholesterol efflux are two working mechanisms by which andrographolide inhibits macrophage foam cell formation, which suggests that andrographolide could be a potential candidate to prevent

  8. Membrane cholesterol removal changes mechanical properties of cells and induces secretion of a specific pool of lysosomes.

    Science.gov (United States)

    Hissa, Barbara; Pontes, Bruno; Roma, Paula Magda S; Alves, Ana Paula; Rocha, Carolina D; Valverde, Thalita M; Aguiar, Pedro Henrique N; Almeida, Fernando P; Guimarães, Allan J; Guatimosim, Cristina; Silva, Aristóbolo M; Fernandes, Maria C; Andrews, Norma W; Viana, Nathan B; Mesquita, Oscar N; Agero, Ubirajara; Andrade, Luciana O

    2013-01-01

    In a previous study we had shown that membrane cholesterol removal induced unregulated lysosomal exocytosis events leading to the depletion of lysosomes located at cell periphery. However, the mechanism by which cholesterol triggered these exocytic events had not been uncovered. In this study we investigated the importance of cholesterol in controlling mechanical properties of cells and its connection with lysosomal exocytosis. Tether extraction with optical tweezers and defocusing microscopy were used to assess cell dynamics in mouse fibroblasts. These assays showed that bending modulus and surface tension increased when cholesterol was extracted from fibroblasts plasma membrane upon incubation with MβCD, and that the membrane-cytoskeleton relaxation time increased at the beginning of MβCD treatment and decreased at the end. We also showed for the first time that the amplitude of membrane-cytoskeleton fluctuation decreased during cholesterol sequestration, showing that these cells become stiffer. These changes in membrane dynamics involved not only rearrangement of the actin cytoskeleton, but also de novo actin polymerization and stress fiber formation through Rho activation. We found that these mechanical changes observed after cholesterol sequestration were involved in triggering lysosomal exocytosis. Exocytosis occurred even in the absence of the lysosomal calcium sensor synaptotagmin VII, and was associated with actin polymerization induced by MβCD. Notably, exocytosis triggered by cholesterol removal led to the secretion of a unique population of lysosomes, different from the pool mobilized by actin depolymerizing drugs such as Latrunculin-A. These data support the existence of at least two different pools of lysosomes with different exocytosis dynamics, one of which is directly mobilized for plasma membrane fusion after cholesterol removal.

  9. Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats

    Science.gov (United States)

    2012-01-01

    Background An increased interest is given to the impact of high fat diet on health worldwide. Abnormalities in lipid metabolism induced by high cholesterol diet (HCD) were reported to exacerbate renal diseases via oxidative stress pathways. Rutin and ascorbic acid showed a protective role against oxidative stress-mediated diseases. Furthermore, both lipid metabolism and tissue response to oxidative stress damage was found to vary according to animal gender. Thus, the objective of this work was to examine possible gender-related differences and the possible protective effects of rutin and ascorbic acid supplementation on high cholesterol diet induced nephrotoxicity. Methods 96 young male and female Wistar albino rats were used. HCD supplemented animals were treated with rutin alone or in combination with ascorbic acid for 6 weeks. Creatinine plasma level was estimated. Furthermore, kidney levels of nucleic acids, total protein, malondialdehyde (MDA), reduced glutathione (GSH), total cholesterol, and triglycerides were determined. Finally, kidney tissues were used for histopathological examination. Results HCD supplementation decreased kidney level of nucleic acids, which was more prominent in female animals. Both vitamin combination significantly attenuated HCD induced decrease in nucleic acids. Moreover, kidney level of MDA was significantly altered by HCD in both genders, which was inhibited by rutin and ascorbic acid alone or in combination in male groups and by both vitamins in female groups. There was a reduction in kidney level of GSH by HCD, especially in male groups, which was attenuated by rutin and ascorbic acid combination. Kidney levels of total cholesterol and triglycerides were significantly increased by HCD supplementation in both genders. Coadministration with rutin and/or ascorbic acid protected from such increase, which was more obvious in both vitamins combination. Histopathological investigation supported vitamins protective effect, which was

  10. Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats.

    Science.gov (United States)

    Al-Rejaie, Salim Salih; Abuohashish, Hatem Mustafa; Alkhamees, Osama Abdelrahman; Aleisa, Abdulaziz Mohammed; Alroujayee, Abdulaziz S

    2012-03-16

    An increased interest is given to the impact of high fat diet on health worldwide. Abnormalities in lipid metabolism induced by high cholesterol diet (HCD) were reported to exacerbate renal diseases via oxidative stress pathways. Rutin and ascorbic acid showed a protective role against oxidative stress-mediated diseases. Furthermore, both lipid metabolism and tissue response to oxidative stress damage was found to vary according to animal gender. Thus, the objective of this work was to examine possible gender-related differences and the possible protective effects of rutin and ascorbic acid supplementation on high cholesterol diet induced nephrotoxicity. 96 young male and female Wistar albino rats were used. HCD supplemented animals were treated with rutin alone or in combination with ascorbic acid for 6 weeks. Creatinine plasma level was estimated. Furthermore, kidney levels of nucleic acids, total protein, malondialdehyde (MDA), reduced glutathione (GSH), total cholesterol, and triglycerides were determined. Finally, kidney tissues were used for histopathological examination. HCD supplementation decreased kidney level of nucleic acids, which was more prominent in female animals. Both vitamin combination significantly attenuated HCD induced decrease in nucleic acids. Moreover, kidney level of MDA was significantly altered by HCD in both genders, which was inhibited by rutin and ascorbic acid alone or in combination in male groups and by both vitamins in female groups. There was a reduction in kidney level of GSH by HCD, especially in male groups, which was attenuated by rutin and ascorbic acid combination. Kidney levels of total cholesterol and triglycerides were significantly increased by HCD supplementation in both genders. Coadministration with rutin and/or ascorbic acid protected from such increase, which was more obvious in both vitamins combination. Histopathological investigation supported vitamins protective effect, which was more prominent in male

  11. Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats

    Directory of Open Access Journals (Sweden)

    Al-Rejaie Salim

    2012-03-01

    Full Text Available Abstract Background An increased interest is given to the impact of high fat diet on health worldwide. Abnormalities in lipid metabolism induced by high cholesterol diet (HCD were reported to exacerbate renal diseases via oxidative stress pathways. Rutin and ascorbic acid showed a protective role against oxidative stress-mediated diseases. Furthermore, both lipid metabolism and tissue response to oxidative stress damage was found to vary according to animal gender. Thus, the objective of this work was to examine possible gender-related differences and the possible protective effects of rutin and ascorbic acid supplementation on high cholesterol diet induced nephrotoxicity. Methods 96 young male and female Wistar albino rats were used. HCD supplemented animals were treated with rutin alone or in combination with ascorbic acid for 6 weeks. Creatinine plasma level was estimated. Furthermore, kidney levels of nucleic acids, total protein, malondialdehyde (MDA, reduced glutathione (GSH, total cholesterol, and triglycerides were determined. Finally, kidney tissues were used for histopathological examination. Results HCD supplementation decreased kidney level of nucleic acids, which was more prominent in female animals. Both vitamin combination significantly attenuated HCD induced decrease in nucleic acids. Moreover, kidney level of MDA was significantly altered by HCD in both genders, which was inhibited by rutin and ascorbic acid alone or in combination in male groups and by both vitamins in female groups. There was a reduction in kidney level of GSH by HCD, especially in male groups, which was attenuated by rutin and ascorbic acid combination. Kidney levels of total cholesterol and triglycerides were significantly increased by HCD supplementation in both genders. Coadministration with rutin and/or ascorbic acid protected from such increase, which was more obvious in both vitamins combination. Histopathological investigation supported vitamins

  12. Chewing reduces sympathetic nervous response to stress and prevents poststress arrhythmias in rats.

    Science.gov (United States)

    Koizumi, So; Minamisawa, Susumu; Sasaguri, Kenichi; Onozuka, Minoru; Sato, Sadao; Ono, Yumie

    2011-10-01

    Reducing stress is important in preventing sudden death in patients with cardiovascular disease, as stressful events may cause autonomic imbalance and trigger fatal arrhythmias. Since chewing has been shown to inhibit stress-induced neuronal responses in the hypothalamus, we hypothesized that chewing could ameliorate stress-induced autonomic imbalance and prevent arrhythmias. To test this hypothesis, we analyzed changes in radiotelemetered electrocardiograms in rats that were allowed to chew a wooden stick during a 1-h period of immobilization stress. Chewing significantly reduced the occurrence of ventricular premature beats (VPBs) and complex ventricular ectopy after immobilization and prevented stress-induced prolongation of the QT interval of VPBs throughout the 10-h experimental period. It also prevented prolongation of the QRS complex and fluctuations in the QT interval in normal sinus rhythm beats preceding VPBs during both immobilization and in the poststress period. Fast Fourier transform-based spectral analysis of heart-rate variability further showed that chewing significantly inhibited the stress-induced increase in the power ratio of low-to-high frequency activity (LF/HF: a marker of sympathetic activity) during immobilization and in addition was associated with blunting of the stress-induced increase in plasma noradrenaline observed at the termination of immobilization. Similar suppressive effects on the occurrence of VPBs and the LF/HF were observed in rats that were administered the β-adrenergic blocker propranolol before immobilization. These results indicate that chewing can ameliorate sympathetic hyperactivity during stress and prevent poststress arrhythmias and suggest that chewing may provide a nonpharmacological and cost-effective treatment option for patients with a high risk of stress-induced fatal arrhythmia.

  13. Pre-treatment with mild whole-body heating prevents gastric ulcer induced by restraint and water-immersion stress in rats.

    Science.gov (United States)

    Itoh, Y H; Noguchi, R

    2000-01-01

    The purpose of this study was to assess the preventive effect of pre-mild whole-body heating (WBH) on gastric ulcer induced by restraint and water-immersion stress. The ulcer index and ulcer area ratio in rats exposed to restraint and water-immersion stress were significantly decreased (p immersion stress alone (p immersion, thereby preventing gastric ulcer formation. Pre-treatment with mild WBH is the safest cytoprotective method through the accumulation of HSP 70f. The concentration of HSP 70f in peripheral lymphocytes may be a useful clinical laboratory indicator for assessing the level of HSP 70f as having cytoprotective activity.

  14. Cannabinoid receptors activation and glucocorticoid receptors deactivation in the amygdala prevent the stress-induced enhancement of a negative learning experience.

    Science.gov (United States)

    Ramot, Assaf; Akirav, Irit

    2012-05-01

    The enhancement of emotional memory is clearly important as emotional stimuli are generally more significant than neutral stimuli for surviving and reproduction purposes. Yet, the enhancement of a negative emotional memory following exposure to stress may result in dysfunctional or intrusive memory that underlies several psychiatric disorders. Here we examined the effects of stress exposure on a negative emotional learning experience as measured by a decrease in the magnitude of the expected quantity of reinforcements in an alley maze. In contrast to other fear-related negative experiences, reward reduction is more associated with frustration and is assessed by measuring the latency to run the length of the alley to consume the reduced quantity of reward. We also examined whether the cannabinoid receptors agonist WIN55,212-2 (5 μg/side) and the glucocorticoid receptors (GRs) antagonist RU-486 (10 ng/side) administered into the rat basolateral amygdala (BLA) could prevent the stress-induced enhancement. We found that intra-BLA RU-486 or WIN55,212 before stress exposure prevented the stress-induced enhancement of memory consolidation for reduction in reward magnitude. These findings suggest that cannabinoid receptors and GRs in the BLA are important modulators of stress-induced enhancement of emotional memory. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig

    International Nuclear Information System (INIS)

    Ceremuzynski, L.K.; Klos, J.; Barcikowski, B.; Herbaczynska-Cedro, K.

    1991-01-01

    A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, the authors studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radioimmunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 x 20 mg p.o. daily for 2 days before and on the day of immobilization, transiently attenuated the stress-induced increase of plasma renin activity and completely prevented the rise of aldosterone, as compared to nontreated controls (N = 10). The finding that nisoldipine suppresses RAA activation induced by a nonpharmacologic stimulus in the conscious intact animal may have clinical implications

  16. Introducing inducible fluorescent split cholesterol oxidase to mammalian cells.

    Science.gov (United States)

    Chernov, Konstantin G; Neuvonen, Maarit; Brock, Ivonne; Ikonen, Elina; Verkhusha, Vladislav V

    2017-05-26

    Cholesterol oxidase (COase) is a bacterial enzyme catalyzing the first step in the biodegradation of cholesterol. COase is an important biotechnological tool for clinical diagnostics and production of steroid drugs and insecticides. It is also used for tracking intracellular cholesterol; however, its utility is limited by the lack of an efficient temporal control of its activity. To overcome this we have developed a regulatable fragment complementation system for COase cloned from Chromobacterium sp. The enzyme was split into two moieties that were fused to FKBP (FK506-binding protein) and FRB (rapamycin-binding domain) pair and split GFP fragments. The addition of rapamycin reconstituted a fluorescent enzyme, termed split GFP-COase, the fluorescence level of which correlated with its oxidation activity. A rapid decrease of cellular cholesterol induced by intracellular expression of the split GFP-COase promoted the dissociation of a cholesterol biosensor D4H from the plasma membrane. The process was reversible as upon rapamycin removal, the split GFP-COase fluorescence was lost, and cellular cholesterol levels returned to normal. These data demonstrate that the split GFP-COase provides a novel tool to manipulate cholesterol in mammalian cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Influence of chronic stress on the compositions of hepatic cholesterol and triglyceride in male Wistar rats fed a high fat diet.

    Science.gov (United States)

    Gao, Siyuan; Han, Xue; Fu, Jihua; Yuan, Xiaoling; Sun, Xing; Li, Qiang

    2012-07-01

      We determined the influence of chronic stress (CS) on the compositions of hepatic cholesterol and triglyceride (TG) in rats fed a high fat diet (HFD).   Male Wistar rats were fed either a standard diet or a HFD and half of the HFD fed rats were given CS (electric foot shock assisted with noise) for 8 weeks.   Compared with the control group, the levels of hepatic total cholesterol (TC) and TG were significantly elevated in the HFD and HFD with chronic stress (HFD+CS) groups, and the more severe elevations of them were found in the HFD group. Inversely, the more severe elevations of hepatic water-soluble parts of TC and TG were found in the HFD+CS group, as the elevations of low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol in liver and serum, tumor necrosis factor-α, interleukin-1β and malondialdehyde in liver. Meanwhile, downregulated mRNA expressions of hepatic liver X receptor-α (LXR-α) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were also more severe in the HFD+CS group.   CS can aggravate the high levels of water-soluble compositions of hepatic TC and TG induced by HFD as it aggravates hepatic inflammation and oxidative stress; in spite of that, however, it cannot further promote hepatic lipidosis. This is consistent with the downregulated mRNA expressions of LXR-α and PPAR-γ. © 2012 The Japan Society of Hepatology.

  18. Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia.

    Science.gov (United States)

    Lee, Li-Chen; Wei, Li; Huang, Wen-Ching; Hsu, Yi-Ju; Chen, Yi-Ming; Huang, Chi-Chang

    2015-12-17

    Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.

  19. Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia

    Directory of Open Access Journals (Sweden)

    Li-Chen Lee

    2015-12-01

    Full Text Available Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD. Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8, standard diet (control; and experimental (n = 32, HCD. The 32 hamsters were further divided into four groups (n = 8 per group to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC, triacylglycerol (TG, high-density lipoprotein cholesterol (HDL-C, and low-density lipoprotein cholesterol (LDL-C, LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.

  20. Effects of an anti-oxidative ACAT inhibitor on apoptosis/necrosis and cholesterol accumulation under oxidative stress in THP-1 cell-derived foam cells.

    Science.gov (United States)

    Miike, Tomohiro; Shirahase, Hiroaki; Jino, Hiroshi; Kunishiro, Kazuyoshi; Kanda, Mamoru; Kurahashi, Kazuyoshi

    2008-01-02

    THP-1 cell-derived foam cells were exposed to oxidative stress through combined treatment with acetylated LDL (acLDL) and copper ions (Cu2+). The foam cells showed caspase-dependent apoptotic changes on exposure to oxidative stress for 6 h, and necrotic changes with the leakage of LDH after 24 h. KY-455, an anti-oxidative ACAT inhibitor, and ascorbic acid (VC) but not YM-750, an ACAT inhibitor, prevented apoptotic and necrotic changes. These preventive effects of KY-455 and VC were accompanied by the inhibition of lipid peroxidation in culture medium containing acLDL and Cu2+, suggesting the involvement of oxidized acLDL in apoptosis and necrosis. Foam cells accumulated esterified cholesterol (EC) for 24 h in the presence of acLDL without Cu2+, which was suppressed by KY-455 and YM-750. Foam cells showed necrotic changes and died in the presence of acLDL and Cu2+. KY-455 but not YM-750 prevented cell death and reduced the amount of EC accumulated. The foam cells treated with VC further accumulated EC without necrotic changes for 24 h even in the presence of acLDL and Cu2+. YM-750 as well as KY-455 inhibited lipid accumulation when co-incubated with VC in foam cells exposed to oxidative stress. It is concluded that an anti-oxidative ACAT inhibitor or the combination of an antioxidant and an ACAT inhibitor protects foam cells from oxidative stress and effectively reduces cholesterol levels, which would be a promising approach in anti-atherosclerotic therapy.

  1. NecroX-7 prevents oxidative stress-induced cardiomyopathy by inhibition of NADPH oxidase activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joonghoon; Park, Eok; Ahn, Bong-Hyun; Kim, Hyoung Jin [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of); Park, Ji-hoon [Department of Biochemistry, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Koo, Sun Young; Kwak, Hyo-Shin; Park, Heui Sul; Kim, Dong Wook; Song, Myoungsub; Yim, Hyeon Joo; Seo, Dong Ook [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of); Kim, Soon Ha, E-mail: shakim@lgls.com [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of)

    2012-08-15

    Oxidative stress is one of the causes of cardiomyopathy. In the present study, NecroXs, novel class of mitochondrial ROS/RNS scavengers, were evaluated for cardioprotection in in vitro and in vivo model, and the putative mechanism of the cardioprotection of NecroX-7 was investigated by global gene expression profiling and subsequent biochemical analysis. NecroX-7 prevented tert-butyl hydroperoxide (tBHP)-induced death of H9C2 rat cardiomyocytes at EC{sub 50} = 0.057 μM. In doxorubicin (DOX)-induced cardiomyopathy in rats, NecroX-7 significantly reduced the plasma levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) which were increased by DOX treatment (p < 0.05). Microarray analysis revealed that 21 genes differentially expressed in tBHP-treated H9C2 cells were involved in ‘Production of reactive oxygen species’ (p = 0.022), and they were resolved by concurrent NecroX-7 treatment. Gene-to-gene networking also identified that NecroX-7 relieved cell death through Ncf1/p47phox and Rac2 modulation. In subsequent biochemical analysis, NecroX-7 inhibited NADPH oxidase (NOX) activity by 53.3% (p < 0.001). These findings demonstrate that NecroX-7, in part, provides substantial protection of cardiomyopathy induced by tBHP or DOX via NOX-mediated cell death. -- Highlights: ► NecroX-7 prevented tert-butyl hydroperoxide-induced in vitro cardiac cell death. ► NecroX-7 ameliorated doxorubicin-induced in vivo cardiomyopathy. ► NecroX-7 prevented oxidative stress and necrosis-enriched transcriptional changes. ► NecroX-7 effectively inhibited NADPH oxidase activation. ► Cardioprotection of Necro-7 was brought on by modulation of NADPH oxidase activity.

  2. Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats

    OpenAIRE

    Al-Rejaie, Salim Salih; Abuohashish, Hatem Mustafa; Alkhamees, Osama Abdelrahman; Aleisa, Abdulaziz Mohammed; Alroujayee, Abdulaziz S

    2012-01-01

    Abstract Background An increased interest is given to the impact of high fat diet on health worldwide. Abnormalities in lipid metabolism induced by high cholesterol diet (HCD) were reported to exacerbate renal diseases via oxidative stress pathways. Rutin and ascorbic acid showed a protective role against oxidative stress-mediated diseases. Furthermore, both lipid metabolism and tissue response to oxidative stress damage was found to vary according to animal gender. Thus, the objective of thi...

  3. Grape juice concentrate prevents oxidative DNA damage in peripheral blood cells of rats subjected to a high-cholesterol diet.

    Science.gov (United States)

    Aguiar, Odair; Gollücke, Andréa Pittelli Boiago; de Moraes, Bárbara Bueno; Pasquini, Gabriela; Catharino, Rodrigo Ramos; Riccio, Maria Francesca; Ihara, Silvia Saiuli Miki; Ribeiro, Daniel Araki

    2011-03-01

    The goal of the present study was to investigate whether subchronic treatment with grape juice concentrate is able to protect liver and peripheral blood cells against cholesterol-induced injury in rats. The effects of the grape juice concentrate treatment on histopathological changes, immunohistochemistry for cyclo-oxygenase-2 (COX-2), and basal and oxidative DNA damage induced by H2O2 using a single-cell gel (comet) assay were evaluated. Male Wistar rats (n 18) were divided into three groups: group 1--negative control; group 2--cholesterol at 1 % (w/w) in their diet, treated for 5 weeks; group 3--cholesterol at 1 % in their chow, treated for 5 weeks, and grape juice concentrate at 222 mg/d in their drinking-water in the final week only. The results indicated that the treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in group 3 compared with group 2. However, grape juice concentrate was able to decrease oxidative DNA damage induced by H2O2 in peripheral blood cells, as depicted by the tail moment results. COX-2 expression in the liver did not show statistically significant differences (P>0·05) between groups. Taken together, the present results suggest that the administration of subchronic grape juice concentrate prevents oxidative DNA damage in peripheral blood cells.

  4. Zinc prevents sickness behavior induced by lipopolysaccharides after a stress challenge in rats.

    Directory of Open Access Journals (Sweden)

    Thiago B Kirsten

    Full Text Available Sickness behavior is considered part of the specific beneficial adaptive behavioral and neuroimmune changes that occur in individuals in response to infectious/inflammatory processes. However, in dangerous and stressful situations, sickness behavior should be momentarily abrogated to prioritize survival behaviors, such as fight or flight. Taking this assumption into account, we experimentally induced sickness behavior in rats using lipopolysaccharides (LPS, an endotoxin that mimics infection by gram-negative bacteria, and then exposed these rats to a restraint stress challenge. Zinc has been shown to play a regulatory role in the immune and nervous systems. Therefore, the objective of this study was to examine the effects of zinc treatment on the sickness response of stress-challenged rats. We evaluated 22-kHz ultrasonic vocalizations, open-field behavior, tumor necrosis factor α (TNF-α, corticosterone, and brain-derived neurotrophic factor (BDNF plasma levels. LPS administration induced sickness behavior in rats compared to controls, i.e., decreases in the distance traveled, average velocity, rearing frequency, self-grooming, and number of vocalizations, as well as an increase in the plasma levels of TNF-α, compared with controls after a stressor challenge. LPS also decreased BDNF expression but did not influence anxiety parameters. Zinc treatment was able to prevent sickness behavior in LPS-exposed rats after the stress challenge, restoring exploratory/motor behaviors, communication, and TNF-α levels similar to those of the control group. Thus, zinc treatment appears to be beneficial for sick animals when they are facing risky/stressful situations.

  5. Cognitive impairment and Alzheimer’s disease: Links with oxidative stress and cholesterol metabolism

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    Alejandra Sekler

    2008-08-01

    Full Text Available Alejandra Sekler1,2, José M Jiménez2, Leonel Rojo2, Edgard Pastene3, Patricio Fuentes4, Andrea Slachevsky4, Ricardo B Maccioni1,21Center of Cognitive Neurosciences, International Center for Biomedicine (ICC, Santiago, Chile; 2Laboratory of Cellular, Molecular Biology and Neurosciences, Faculty of Sciences, Universidad de Chile, Santiago, Chile; 3Department of Pharmacy, Faculty of Pharmacy, University of Concepcion, Concepción, Chile; 4Unidad de Neurología Cognitiva y Demencias, Servicio de Neurología, Hospital del Salvador, Santiago, ChileAbstract: Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer’s disease (AD, Parkinson’s disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP, plasma malondialdehyde and total antioxidative capacity (TAC, as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59 and a control group of neurologically normal subjects (n = 29, attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery, while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC of

  6. Calcium dobesilate prevents the oxidative stress and inflammation induced by diabetes in the retina of db/db mice.

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    Bogdanov, Patricia; Solà-Adell, Cristina; Hernández, Cristina; García-Ramírez, Marta; Sampedro, Joel; Simó-Servat, Olga; Valeri, Marta; Pasquali, Christian; Simó, Rafael

    2017-10-01

    Calcium dobesilate (CaD) is beneficial in early stages of diabetic retinopathy (DR), but its mechanisms of action remains to be elucidated. The aim was to investigate the effect of CaD on proinflammatory cytokines and oxidative stress. db/db mice were randomly assigned to daily oral treatment with CaD (200mg/kg/day) or vehicle for 15days. Biomarkers of oxidative stress (dihydroethidium, malondialdehyde), NF-κB, and proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, MCP-1) were examined in the retina by immunohistochemical analysis. Cultures of human retinal endothelial cells (HRECs) were used for complementary experiments. CaD significantly reduced the biomarkers of oxidative stress in the retina of db/db mice. In addition, CaD prevented the increase of NF-κB, IL-6, IL-8, TNF-α and MCP-1 induced by diabetes. CaD inhibited the activation of NF-kβ induced by IL-1β by preventing IKKB-α phosphorylation in HRECs and reduced the upregulation of IL-6 and IL-18 induced by TNF-α in a dose-dependent manner. Our results suggest that antioxidant and antiinflammatory effects are crucial in accounting for the effectiveness of CaD for treating DR. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Caffeine prevents d-galactose-induced cognitive deficits, oxidative stress, neuroinflammation and neurodegeneration in the adult rat brain.

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    Ullah, Faheem; Ali, Tahir; Ullah, Najeeb; Kim, Myeong Ok

    2015-11-01

    d-galactose has been considered a senescent model for age-related neurodegenerative disease. It induces oxidative stress which triggers memory impairment, neuroinflammation and neurodegeneration. Caffeine act as anti-oxidant and has been used in various model of neurodegenerative disease. Nevertheless, the effect of caffeine against d-galactose aging murine model of age-related neurodegenerative disease elucidated. Here, we investigated the neuroprotective effect of caffeine against d-galactose. We observed that chronic treatment of caffeine (3 mg/kg/day intraperitoneally (i.p) for 60 days) improved memory impairment and synaptic markers (Synaptophysin and PSD95) in the d-galactose treated rats. Chronic caffeine treatment reduced the oxidative stress via the reduction of 8-oxoguanine through immunofluorescence in the d-galactose-treated rats. Consequently caffeine treatment suppressed stress kinases p-JNK. Additionally, caffeine treatment significantly reduced the d-galactose-induced neuroinflammation through alleviation of COX-2, NOS-2, TNFα and IL-1β. Furthermore we also analyzed that caffeine reduced cytochrome C, Bax/Bcl2 ratio, caspase-9, caspase-3 and PARP-1 level. Moreover by evaluating the immunohistochemical results of Nissl and Fluro-Jade B staining showed that caffeine prevented the neurodegeneration in the d-galactose-treated rats. Our results showed that caffeine prevents the d-galactose-induced oxidative stress and consequently alleviated neuroinflammation and neurodegeneration; and synaptic dysfunction and memory impairment. Therefore, we could suggest that caffeine might be a dietary anti-oxidant agent and a good candidate for the age-related neurodegenerative disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Taurine Pretreatment Prevents Isoflurane-Induced Cognitive Impairment by Inhibiting ER Stress-Mediated Activation of Apoptosis Pathways in the Hippocampus in Aged Rats.

    Science.gov (United States)

    Zhang, Yanan; Li, Dongliang; Li, Haiou; Hou, Dailiang; Hou, Jingdong

    2016-10-01

    Isoflurane, a commonly used inhalation anesthetic, may induce neurocognitive deficits, especially in elderly patients after surgery. Recent study demonstrated that isoflurane caused endoplasmic reticulum (ER) stress and subsequent neuronal apoptosis in the brain, contributing to cognitive deficits. Taurine, a major intracellular free amino acid, has been shown to inhibit ER stress and neuronal apoptosis in several neurological disorders. Here, we examined whether taurine can prevent isoflurane-induced ER stress and cognitive impairment in aged rats. Thirty minutes prior to a 4-h 1.3 % isoflurane exposure, aged rats were treated with vehicle or taurine at low, middle and high doses. Aged rats without any treatment served as control. The brains were harvested 6 h after isoflurane exposure for molecular measurements, and behavioral study was performed 2 weeks later. Compared with control, isoflurane increased expression of hippocampal ER stress biomarkers including glucose-regulated protein 78, phosphorylated (P-) inositol-requiring enzyme 1, P-eukaryotic initiation factor 2-α (EIF2α), activating transcription factor 4 (ATF-4), cleaved ATF-6 and C/EBP homologous protein, along with activation of apoptosis pathways as indicated by decreased B cell lymphoma 2 (BCL-2)/BCL2-associated X protein, increased expressions of cytochrome-c and cleaved caspase-3. Taurine pretreatment dose-dependently inhibited isoflurane-induced increase in expression of ER stress biomarkers except for P-EIF2α and ATF-4, and reversed isoflurane-induced changes in apoptosis-related proteins. Moreover, isoflurane caused spatial working memory deficits in aged rats, which were prevented by taurine pretreatment. The results indicate that taurine pretreatment prevents anesthetic isoflurane-induced cognitive impairment by inhibiting ER stress-mediated activation of apoptosis pathways in the hippocampus in aged rats.

  9. BL153 Partially Prevents High-Fat Diet Induced Liver Damage Probably via Inhibition of Lipid Accumulation, Inflammation, and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Jian Wang

    2014-01-01

    Full Text Available The present study was to investigate whether a magnolia extract, named BL153, can prevent obesity-induced liver damage and identify the possible protective mechanism. To this end, obese mice were induced by feeding with high fat diet (HFD, 60% kcal as fat and the age-matched control mice were fed with control diet (10% kcal as fat for 6 months. Simultaneously these mice were treated with or without BL153 daily at 3 dose levels (2.5, 5, and 10 mg/kg by gavage. HFD feeding significantly increased the body weight and the liver weight. Administration of BL153 significantly reduced the liver weight but without effects on body weight. As a critical step of the development of NAFLD, hepatic fibrosis was induced in the mice fed with HFD, shown by upregulating the expression of connective tissue growth factor and transforming growth factor beta 1, which were significantly attenuated by BL153 in a dose-dependent manner. Mechanism study revealed that BL153 significantly suppressed HFD induced hepatic lipid accumulation and oxidative stress and slightly prevented liver inflammation. These results suggest that HFD induced fibrosis in the liver can be prevented partially by BL153, probably due to reduction of hepatic lipid accumulation, inflammation and oxidative stress.

  10. [Nutritional approaches to modulate oxidative stress that induce Alzheimer's disease. Nutritional approaches to prevent Alzheimer's disease].

    Science.gov (United States)

    Lara, Humberto Herman; Alanís-Garza, Eduardo Javier; Estrada Puente, María Fernanda; Mureyko, Lucía Liliana; Alarcón Torres, David Alejandro; Ixtepan Turrent, Liliana

    2015-01-01

    Alzheimer's disease is the most common cause of dementia in the world; symptoms first appear after age 65 and have a progressive evolution. Expecting an increase on its incidence and knowing there is currently no cure for Alzheimer's disease, it is a necessity to prevent progression. The change in diet due to globalization may explain the growth of the incidence in places such as Japan and Mediterranean countries, which used to have fewer incidences. There is a direct correlation between disease progression and the increased intake of alcohol, saturated fats, and red meat. Therefore, we find obesity and higher serum levels in cholesterol due to saturated fat as a result. A way to decrease the progression of Alzheimer's is through a diet rich in polipheno/es (potent antioxidants), unsaturated fats (monounsaturated and polyunsaturated), fish, vegetable fa t, fruits with low glycemic index, and a moderate consumption of red wine. Through this potent antioxidant diet we accomplish the prevention of dementia and the progression of Alzheimer's disease. This article emphasizes the food and other components that have been demonstrated to decrease the oxidative stress related to these progressive diseases.

  11. Structure-activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro.

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    Hammad, Ayat S; Ravindran, Sreenithya; Khalil, Ashraf; Munusamy, Shankar

    2017-05-01

    Endoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD. Piperine and its analogs have been reported to exhibit multiple pharmacological activities; however, their efficacy against ER stress in kidney cells has not been studied yet. Hence, the goal of this study was to synthesize amide-substituted piperine analogs and screen them for pharmacological activity to relieve ER stress using an in vitro model of tunicamycin-induced ER stress using normal rat kidney (NRK-52E) cells. Five amide-substituted piperine analogs were synthesized and their chemical structures were elucidated by pertinent spectroscopic techniques. An in vitro model of ER stress was developed using tunicamycin, and the compounds of interest were screened for their effect on cell viability, and the expression of ER chaperone GRP78, the pro-apoptotic ER stress marker CHOP, and apoptotic caspases 3 and 12 (via western blotting). Our findings indicate that exposure to tunicamycin (0.5 μg/mL) for 2 h induces the expression of GRP78 and CHOP, and apoptotic markers (caspase-3 and caspase-12) and causes a significant reduction in renal cell viability. Pre-treatment of cells with piperine and its cyclohexylamino analog decreased the tunicamycin-induced upregulation of GRP78 and CHOP and cell death. Taken together, our findings demonstrate that piperine and its analogs differentially regulate ER stress, and thus represent potential therapeutic agents to treat ER stress-related renal disorders. Graphical Abstract Piperine (PIP) reduces the expression of ER stress markers (GRP78 and CHOP) induced by pathologic stimuli and consequently decreases the activation of apoptotic caspase-12 and caspase-3; all of which contributes to its chemical chaperone and cytoprotective properties to protect

  12. Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative Stress and Dysfunctions in Cultured Rat Cortical Neurons.

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    Qu, Mingyue; Jiang, Zheng; Liao, Yuanxiang; Song, Zhenyao; Nan, Xinzhong

    2016-06-01

    Brains affected by Alzheimer's disease (AD) show a large spectrum of mitochondrial alterations at both morphological and genetic level. The causal link between β-amyloid (Aβ) and mitochondrial dysfunction has been established in cellular models of AD. We observed previously that lycopene, a member of the carotenoid family of phytochemicals, could counteract neuronal apoptosis and cell damage induced by Aβ and other neurotoxic substances, and that this neuroprotective action somehow involved the mitochondria. The present study aims to investigate the effects of lycopene on mitochondria in cultured rat cortical neurons exposed to Aβ. It was found that lycopene attenuated Aβ-induced oxidative stress, as evidenced by the decreased intracellular reactive oxygen species generation and mitochondria-derived superoxide production. Additionally, lycopene ameliorated Aβ-induced mitochondrial morphological alteration, opening of the mitochondrial permeability transition pores and the consequent cytochrome c release. Lycopene also improved mitochondrial complex activities and restored ATP levels in Aβ-treated neuron. Furthermore, lycopene prevented mitochondrial DNA damages and improved the protein level of mitochondrial transcription factor A in mitochondria. Those results indicate that lycopene protects mitochondria against Aβ-induced damages, at least in part by inhibiting mitochondrial oxidative stress and improving mitochondrial function. These beneficial effects of lycopene may account for its protection against Aβ-induced neurotoxicity.

  13. Oxidative stress and hemoglobin-cholesterol adduct in renal patients with different LDL phenotypes.

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    Miljkovic, Milica; Kotur-Stevuljevic, Jelena; Stefanovic, Aleksandra; Zeljkovic, Aleksandra; Vekic, Jelena; Gojkovic, Tamara; Bogavac-Stanojevic, Natasa; Nikolic, Milan; Simic-Ogrizovic, Sanja; Spasojevic-Kalimanovska, Vesna; Jelic-Ivanovic, Zorana

    2016-10-01

    Unfavorable lipid profile is a major risk factor for cardiovascular disease in renal pathology. In this study, we compared chronic renal patients and healthy controls with different LDL phenotypes (A or B) in respect of various biochemical parameters related to cardiovascular disease. Oxidative stress and anti-oxidative defense parameters [thiobarbituric acid-reacting substances (TBARS), total oxidative status (TOS), total anti-oxidative status (TAS), total protein sulfhydryl (-SH) groups], as well as red blood cell cholesterol distribution were assessed in 40 renal patients and 40 control subjects by standardized assays. LDL particle diameters were determined by polyacrylamide gradient gel electrophoresis. LDL particles are subdivided according to their size into large LDL A phenotype (diameter >25.5 nm) and small LDL B phenotype (diameter ≤25.5 nm). Renal patients with LDL A phenotype had increased oxidative stress (TOS: p LDL phenotype. A notable decrease in hemoglobin-cholesterol adduct was detected in patients with LDL A phenotype (p LDL B phenotype (p LDL B phenotype was characterized with increased TBARS (p LDL A phenotype in control group. Increased oxidative stress, decreased anti-oxidative defense followed with unfavorable changes in hemoglobin-cholesterol binding capacity, could have important influence on cardiovascular disease risk in renal patients regardless of LDL phenotype.

  14. Kefir prevented excess fat accumulation in diet-induced obese mice.

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    Choi, Jae-Woo; Kang, Hye Won; Lim, Won-Chul; Kim, Mi-Kyoung; Lee, In-Young; Cho, Hong-Yon

    2017-05-01

    Excessive body fat accumulation can result in obesity, which is a serious health concern. Kefir, a probiotic, has recently shown possible health benefits in fighting obesity. This study investigated the inhibitory effects of 0.1 and 0.2% kefir powder on fat accumulation in adipose and liver tissues of high-fat diet (HFD)-induced obese mice. Kefir reduced body weight and epididymal fat pad weight and decreased adipocyte diameters in HFD-induced obese mice. This was supported by decreased expression of genes related to adipogenesis and lipogenesis as well as reduced proinflammatory marker levels in epididymal fat. Along with reduced hepatic triacylglycerol concentrations and serum alanine transaminase and aspartate transaminase activities, genes related to lipogenesis and fatty acid oxidation were downregulated and upregulated, respectively, in liver tissue. Kefir also decreased serum triacylglycerol, total cholesterol, and low-density lipoprotein-cholesterol concentrations. Overall, kefir has the potential to prevent obesity.

  15. Treatment of silymarin, a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin.

    Science.gov (United States)

    Katiyar, Santosh K

    2002-12-01

    It is well documented that ultraviolet (UV) light-induced immune suppression and oxidative stress play an important role in the induction of skin cancers. Earlier, we have shown that topical treatment of silymarin, a plant flavonoid from milk thistle (Silybum marianum L. Gaertn.), to mouse skin prevents photocarcinogenesis, but the preventive mechanism of photocarcinogenesis in vivo animal system by silymarin is not well defined and understood. To define the mechanism of prevention, we employed immunostaining, analytical assays and ELISA which revealed that topical treatment of silymarin (1 mg/cm2 skin area) to C3H/HeN mice inhibits UVB (90 mJ/cm2)-induced suppression of contact hypersensitivity (CHS) response to contact sensitizer dinitrofluorobenzene. Prevention of UVB-induced suppression of CHS by silymarin was found to be associated with the inhibition of infiltrating leukocytes, particularly CD11b+ cell type, and myeloperoxidase activity (50-71%). Silymarin treatment also resulted in significant reduction of UVB-induced immunosuppressive cytokine interleukin-10 producing cells and its production (58-72%, pskin cancer risk human population and ii) development of sunscreen containing silymarin as an antioxidant (chemopreventive agent) or silymarin can be supplemented in skin care products.

  16. Curcumin Induces Nrf2 Nuclear Translocation and Prevents Glomerular Hypertension, Hyperfiltration, Oxidant Stress, and the Decrease in Antioxidant Enzymes in 5/6 Nephrectomized Rats

    Directory of Open Access Journals (Sweden)

    Edilia Tapia

    2012-01-01

    Full Text Available Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1 control, (2 5/6NX, (3 5/6NX +CUR, and (4 CUR (n=8–10. Curcumin was given by gavage to NX5/6 +CUR and CUR groups (60 mg/kg/day starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes.

  17. Aerobic exercise acutely prevents the endothelial dysfunction induced by mental stress among subjects with metabolic syndrome: the role of shear rate.

    Science.gov (United States)

    Sales, Allan R K; Fernandes, Igor A; Rocha, Natália G; Costa, Lucas S; Rocha, Helena N M; Mattos, João D M; Vianna, Lauro C; Silva, Bruno M; Nóbrega, Antonio C L

    2014-04-01

    Mental stress induces transient endothelial dysfunction, which is an important finding for subjects at cardiometabolic risk. Thus, we tested whether aerobic exercise prevents this dysfunction among subjects with metabolic syndrome (MetS) and whether an increase in shear rate during exercise plays a role in this phenomenon. Subjects with MetS participated in two protocols. In protocol 1 (n = 16), endothelial function was assessed using brachial artery flow-mediated dilation (FMD). Subjects then underwent a mental stress test followed by either 40 min of leg cycling or rest across two randomized sessions. FMD was assessed again at 30 and 60 min after exercise or rest, with a second mental stress test in between. Mental stress reduced FMD at 30 and 60 min after the rest session (baseline: 7.7 ± 0.4%, 30 min: 5.4 ± 0.5%, and 60 min: 3.9 ± 0.5%, P exercise prevented this reduction (baseline: 7.5 ± 0.4%, 30 min: 7.2 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline). Protocol 2 (n = 5) was similar to protocol 1 except that the first period of mental stress was followed by either exercise in which the brachial artery shear rate was attenuated via forearm cuff inflation or exercise without a cuff. Noncuffed exercise prevented the reduction in FMD (baseline: 7.5 ± 0.7%, 30 min: 7.0 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline), whereas cuffed exercise failed to prevent this reduction (baseline: 7.5 ± 0.6%, 30 min: 5.4 ± 0.8%, and 60 min: 4.1 ± 0.9%, P exercise prevented mental stress-induced endothelial dysfunction among subjects with MetS, and an increase in shear rate during exercise mediated this effect.

  18. Stevia Prevents Acute and Chronic Liver Injury Induced by Carbon Tetrachloride by Blocking Oxidative Stress through Nrf2 Upregulation

    Science.gov (United States)

    Ramos-Tovar, Erika; Hernández-Aquino, Erika; Casas-Grajales, Sael; Buendia-Montaño, Laura D.; Tsutsumi, Víctor

    2018-01-01

    The effect of stevia on liver cirrhosis has not been previously investigated. In the present study, the antioxidant and anti-inflammatory properties of stevia leaves were studied in male Wistar rats with carbon tetrachloride- (CCl4-) induced acute and chronic liver damage. Acute and chronic liver damage induced oxidative stress, necrosis, and cholestasis, which were significantly ameliorated by stevia. Chronic CCl4 treatment resulted in liver cirrhosis, as evidenced by nodules of hepatocytes surrounded by thick bands of collagen and distortion of the hepatic architecture, and stevia significantly prevented these alterations. Subsequently, the underlying mechanism of action of the plant was analyzed. Our study for the first time shows that stevia upregulated Nrf2, thereby counteracting oxidative stress, and prevented necrosis and cholestasis through modulation of the main proinflammatory cytokines via NF-κB inhibition. These multitarget mechanisms led to the prevention of experimental cirrhosis. Given the reasonable safety profile of stevia, our results indicated that it may be useful for the clinical treatment of acute and chronic liver diseases. PMID:29849889

  19. Effect of atorvastatin on hyperglycemia-induced brain oxidative stress and neuropathy induced by diabetes

    Directory of Open Access Journals (Sweden)

    Nastaran Faghihi

    2015-04-01

    Conclusion: The findings of the present study reveal that atorvastatin is able to prevent hyperglycemia-induced diabetic neuropathy and inhibit brain oxidative stress during diabetes. It is probable that reduction of urea is one of the reasons for atorvastatin prevention of hyperglycemia-induced neuropathy.

  20. Chronic mitochondrial uncoupling treatment prevents acute cold-induced oxidative stress in birds.

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    Stier, Antoine; Massemin, Sylvie; Criscuolo, François

    2014-12-01

    Endotherms have evolved two major types of thermogenesis that allow them to actively produce heat in response to cold exposure, either through muscular activity (i.e. shivering thermogenesis) or through futile electro-chemical cycles (i.e. non-shivering thermogenesis). Amongst the latter, mitochondrial uncoupling is of key importance because it is suggested to drive heat production at a low cost in terms of oxidative stress. While this has been experimentally shown in mammals, the oxidative stress consequences of cold exposure and mitochondrial uncoupling are clearly less understood in the other class of endotherms, the birds. We compared metabolic and oxidative stress responses of zebra finches chronically treated with or without a chemical mitochondrial uncoupler (2,4-dinitrophenol: DNP), undergoing an acute (24 h) and a chronic (4 weeks) cold exposure (12 °C). We predicted that control birds should present at least a transient elevation of oxidative stress levels in response to cold exposure. This oxidative stress cost should be more pronounced in control birds than in DNP-treated birds, due to their lower basal uncoupling state. Despite similar increase in metabolism, control birds presented elevated levels of DNA oxidative damage in response to acute (but not chronic) cold exposure, while DNP-treated birds did not. Plasma antioxidant capacity decreased overall in response to chronic cold exposure. These results show that acute cold exposure increases oxidative stress in birds. However, uncoupling mitochondrial functioning appears as a putative compensatory mechanism preventing cold-induced oxidative stress. This result confirms previous observations in mice and underlines non-shivering thermogenesis as a putative key mechanism for endotherms in mounting a response to cold at a low oxidative cost.

  1. Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis.

    Science.gov (United States)

    Gao, Yansong; Zhou, Yulian; Goldstein, Joseph L; Brown, Michael S; Radhakrishnan, Arun

    2017-05-26

    Scap is a polytopic protein of endoplasmic reticulum (ER) membranes that transports sterol regulatory element-binding proteins to the Golgi complex for proteolytic activation. Cholesterol accumulation in ER membranes prevents Scap transport and decreases cholesterol synthesis. Previously, we provided evidence that cholesterol inhibition is initiated when cholesterol binds to loop 1 of Scap, which projects into the ER lumen. Within cells, this binding causes loop 1 to dissociate from loop 7, another luminal Scap loop. However, we have been unable to demonstrate this dissociation when we added cholesterol to isolated complexes of loops 1 and 7. We therefore speculated that the dissociation requires a conformational change in the intervening polytopic sequence separating loops 1 and 7. Here we demonstrate such a change using a protease protection assay in sealed membrane vesicles. In the absence of cholesterol, trypsin or proteinase K cleaved cytosolic loop 4, generating a protected fragment that we visualized with a monoclonal antibody against loop 1. When cholesterol was added to these membranes, cleavage in loop 4 was abolished. Because loop 4 is part of the so-called sterol-sensing domain separating loops 1 and 7, these results support the hypothesis that cholesterol binding to loop 1 alters the conformation of the sterol-sensing domain. They also suggest that this conformational change helps transmit the cholesterol signal from loop 1 to loop 7, thereby allowing separation of the loops and facilitating the feedback inhibition of cholesterol synthesis. These insights suggest a new structural model for cholesterol-mediated regulation of Scap activity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. The Effect of the Cholesterol Levels on Noise-Induced Hearing Loss.

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    Demir, Mehmet Gokhan; Aydin, Sedat

    2018-01-01

    Introduction  Noise-induced hearing loss (NIHL), which is one of the most common occupational diseases among industrialized populations, is associated with longstanding exposure to high levels of noise. The pathogenesis of NIHL is not clear, but some genes and their activity at the tissue level have been investigated. Hypercholesterolemia, which can disturb the microcirculation, can be one of the underlying pathologies in hearing loss. Objective  To investigate the relationship between NIHL and hypercholesterolemia. Methods  The study group was selected among workers who had an occupational exposure of 85 dB of noise for at least 10 years. The audiologic assessment was recorded at seven frequencies (500 Hz, 1,000 Hz, 2,000 Hz, 3,000 Hz, 4,000 Hz, 6,000 Hz and 8,000 Hz). A total of 456 workers were included in the study and divided into two groups: the control group (252 patients) and the NIHL group (204 patients). After the audiologic measurement, blood samples were taken and investigated for blood cholesterol levels. According to these results, the groups were compared. Results  Both groups were similarly distributed regarding age and occupational exposure time ( p  > 0.05). We could not detect any association between cholesterol levels and noise-induced hearing loss ( p   0.05). Conclusion  Noise-induced hearing loss is still a common occupational problem that can be prevented by hearing conservation programs and occupational health and safety training. Still, we know little about the relationship between NIHL and hypercholesterolemia. According to our findings, we cannot detect any relationship. Controlled studies and studies with human individuals can be made possible in the future with diagnostic innovations in tissue imaging and tissue microcircular sampling.

  3. Selol, an organic selenium donor, prevents lipopolysaccharide-induced oxidative stress and inflammatory reaction in the rat brain.

    Science.gov (United States)

    Dominiak, Agnieszka; Wilkaniec, Anna; Jęśko, Henryk; Czapski, Grzegorz A; Lenkiewicz, Anna M; Kurek, Eliza; Wroczyński, Piotr; Adamczyk, Agata

    2017-09-01

    Neuroinflammation and oxidative stress are key intertwined pathological factors in many neurological, particularly neurodegenerative diseases, such as Alzheimer's and Parkinson's disorders as well as autism. The present study was conducted to evaluate the protective effects of Selol, an organic selenium donor, against lipopolysaccharide (LPS)-mediated inflammation in rat brain. The results demonstrated that the peripheral administration of LPS in a dose of 100 μg/kg b.w. evoked typical pathological reaction known as systemic inflammatory response. Moreover, we observed elevated blood levels of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress, as well as increased concentration of tumor necrosis factor-α (TNF-α) in LPS-treated animals. Selol significantly prevented these LPS-evoked changes. Subsequently, Selol protected against LPS-induced up-regulation of proinflammatory cytokines (Tnfa, Ifng, Il6) in rat brain cortex. The molecular mechanisms through which Selol prevented the neuroinflammation were associated with the inhibition of oxidized glutathione (GSSG) accumulation and with an increase of glutathione-associated enzymes: glutathione peroxidase (Se-GPx), glutathione reductase (GR) as well as thioredoxin reductase (TrxR) activity and expression. Finally, we observed that Selol administration effectively protected against LPS-induced changes in the expression of brain-derived neurotrophic factor (Bdnf). In conclusion, our studies indicated that Selol effectively protects against LPS-induced neuroinflammation by inhibiting pro-inflammatory cytokine release, by boosting antioxidant systems, and by augmenting BDNF level. Therefore, Selol could be a multi-potent and effective drug useful in the treatment and prevention of brain disorders associated with neuroinflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Inulin and Fibersol-2 Combined Have Hypolipidemic Effects on High Cholesterol Diet-Induced Hyperlipidemia in Hamsters

    Directory of Open Access Journals (Sweden)

    Wen-Ching Huang

    2016-03-01

    Full Text Available The resistant carbohydrates, inulin, and Fibersol-2, belong to soluble dietary fibers and are considered important prebiotics that maintain biological functions, including glucose homeostasis, lipid regulation, colon disease prevention, and prebiotics characteristics. However, few studies have investigated Fibersol-2 alone or in combination with inulin to assess a pooled effect on modulation of hyperlipidemia. We aimed to investigate the effects of this combined supplement (defined as InF on hamsters fed a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet, HCD to induce hyperlipidemia. A total of 40 male hamsters were randomly assigned to five groups (n = 8 per group for treatment: standard diet, vehicle (control; or vehicle or InF supplementation by oral gavage at 0, 864, 1727, or 2591 mg/kg/day for eight weeks, designated HCD, InF-1X, InF-2X, and InF-3X groups, respectively. The hypolipidemic efficacy and safety of InF supplementation was assessed by serum lipid indexes, hepatic and fecal lipid content, and histology. InF supplementation significantly improved serum levels of triacylglycerol (TG and low-density lipoprotein cholesterol (LDL-C and the ratio of LDL-C/HDL-C after two-week treatment, and reduced serum total cholesterol (TC levels after four-week administration. After eight-week supplementation, InF supplementation dose-dependently improved serum levels of TC, TG, HDL-C, and LDL-C; LDL-C/HDL-C ratio; and hepatic TC and TG levels. It inhibited TC absorption by feces elimination. Our study provides experiment-based evidence to support that this prebiotics remedy may be useful in preventing or treating hyperlipidemia.

  5. Markers of Oxidative Stress in Dogs with Myxomatous Mitral Valve Disease are Influenced by Sex, Neuter Status, and Serum Cholesterol Concentration

    DEFF Research Database (Denmark)

    Reimann, M J; Häggström, J; Møller, J E

    2017-01-01

    -tocopherol [P = .003]) was associated with body condition score (BCS), but the association disappeared when cholesterol was included in the analyses. All markers of oxidative stress (MDA, oxLDL, and vitamin E) were positively associated with serum cholesterol concentration (P ≤ .04), but none were associated...... with clinical stage of MMVD. CONCLUSIONS: In conclusion, markers of oxidative stress are associated with sex, BCS, neuter status, and cholesterol. The results cannot confirm a relationship between oxidative stress and clinical stage of the disease in dogs with MMVD....

  6. EPA:DHA 6:1 prevents angiotensin II-induced hypertension and endothelial dysfunction in rats: role of NADPH oxidase- and COX-derived oxidative stress.

    Science.gov (United States)

    Niazi, Zahid Rasul; Silva, Grazielle C; Ribeiro, Thais Porto; León-González, Antonio J; Kassem, Mohamad; Mirajkar, Abdur; Alvi, Azhar; Abbas, Malak; Zgheel, Faraj; Schini-Kerth, Valérie B; Auger, Cyril

    2017-12-01

    Eicosapentaenoic acid:docosahexaenoic acid (EPA:DHA) 6:1, an omega-3 polyunsaturated fatty acid formulation, has been shown to induce a sustained formation of endothelial nitric oxide (NO) synthase-derived NO, a major vasoprotective factor. This study examined whether chronic intake of EPA:DHA 6:1 prevents hypertension and endothelial dysfunction induced by angiotensin II (Ang II) in rats. Male Wister rats received orally corn oil or EPA:DHA 6:1 (500 mg kg -1 per day) before chronic infusion of Ang II (0.4 mg kg -1 per day). Systolic blood pressure was determined by tail cuff sphingomanometry, vascular reactivity using a myograph, oxidative stress using dihydroethidium and protein expression by immunofluorescence and western blot analysis. Ang II-induced hypertension was associated with reduced acetylcholine-induced relaxations of secondary branch mesenteric artery rings affecting the endothelium-dependent hyperpolarization (EDH)- and the NO-mediated relaxations, both of which were improved by the NADPH oxidase inhibitor VAS-2870. The Ang II treatment induced also endothelium-dependent contractile responses (EDCFs), which were abolished by the cyclooxygenase (COX) inhibitor indomethacin. An increased level of vascular oxidative stress and expression of NADPH oxidase subunits (p47 phox and p22 phox ), COX-1 and COX-2, endothelial NO synthase and Ang II type 1 receptors were observed in the Ang II group, whereas SK Ca and connexin 37 were downregulated. Intake of EPA:DHA 6:1 prevented the Ang II-induced hypertension and endothelial dysfunction by improving both the NO- and EDH-mediated relaxations, and by reducing EDCFs and the expression of target proteins. The present findings indicate that chronic intake of EPA:DHA 6:1 prevented the Ang II-induced hypertension and endothelial dysfunction in rats, most likely by preventing NADPH oxidase- and COX-derived oxidative stress.

  7. Mig-6 plays a critical role in the regulation of cholesterol homeostasis and bile acid synthesis.

    Directory of Open Access Journals (Sweden)

    Bon Jeong Ku

    Full Text Available The disruption of cholesterol homeostasis leads to an increase in cholesterol levels which results in the development of cardiovascular disease. Mitogen Inducible Gene 6 (Mig-6 is an immediate early response gene that can be induced by various mitogens, stresses, and hormones. To identify the metabolic role of Mig-6 in the liver, we conditionally ablated Mig-6 in the liver using the Albumin-Cre mouse model (Alb(cre/+Mig-6(f/f; Mig-6(d/d. Mig-6(d/d mice exhibit hepatomegaly and fatty liver. Serum levels of total, LDL, and HDL cholesterol and hepatic lipid were significantly increased in the Mig-6(d/d mice. The daily excretion of fecal bile acids was significantly decreased in the Mig-6(d/d mice. DNA microarray analysis of mRNA isolated from the livers of these mice showed alterations in genes that regulate lipid metabolism, bile acid, and cholesterol synthesis, while the expression of genes that regulate biliary excretion of bile acid and triglyceride synthesis showed no difference in the Mig-6(d/d mice compared to Mig-6(f/f controls. These results indicate that Mig-6 plays an important role in cholesterol homeostasis and bile acid synthesis. Mice with liver specific conditional ablation of Mig-6 develop hepatomegaly and increased intrahepatic lipid and provide a novel model system to investigate the genetic and molecular events involved in the regulation of cholesterol homeostasis and bile acid synthesis. Defining the molecular mechanisms by which Mig-6 regulates cholesterol homeostasis will provide new insights into the development of more effective ways for the treatment and prevention of cardiovascular disease.

  8. Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits.

    Science.gov (United States)

    Wang, Chuan; Nishijima, Kazutoshi; Kitajima, Shuji; Niimi, Manabu; Yan, Haizhao; Chen, Yajie; Ning, Bo; Matsuhisa, Fumikazu; Liu, Enqi; Zhang, Jifeng; Chen, Y Eugene; Fan, Jianglin

    2017-07-01

    Endothelial lipase (EL) is a key determinant in plasma high-density lipoprotein-cholesterol. However, functional roles of EL on the development of atherosclerosis have not been clarified. We investigated whether hepatic expression of EL affects plasma lipoprotein metabolism and cholesterol diet-induced atherosclerosis. We generated transgenic (Tg) rabbits expressing the human EL gene in the liver and then examined the effects of EL expression on plasma lipids and lipoproteins and compared the susceptibility of Tg rabbits with cholesterol diet-induced atherosclerosis with non-Tg littermates. On a chow diet, hepatic expression of human EL in Tg rabbits led to remarkable reductions in plasma levels of total cholesterol, phospholipids, and high-density lipoprotein-cholesterol compared with non-Tg controls. On a cholesterol-rich diet for 16 weeks, Tg rabbits exhibited significantly lower hypercholesterolemia and less atherosclerosis than non-Tg littermates. In Tg rabbits, gross lesion area of aortic atherosclerosis was reduced by 52%, and the lesions were characterized by fewer macrophages and smooth muscle cells compared with non-Tg littermates. Increased hepatic expression of EL attenuates cholesterol diet-induced hypercholesterolemia and protects against atherosclerosis. © 2017 American Heart Association, Inc.

  9. Cholesterol-producing transgenic Caenorhabditis elegans lives longer due to newly acquired enhanced stress resistance

    International Nuclear Information System (INIS)

    Lee, Eun-Young; Shim, Yhong-Hee; Chitwood, David J.; Hwang, Soon Baek; Lee, Junho; Paik, Young-Ki

    2005-01-01

    Because Caenorhabditis elegans lacks several components of the de novo sterol biosynthetic pathway, it requires sterol as an essential nutrient. Supplemented cholesterol undergoes extensive enzymatic modification in C. elegans to form other sterols of unknown function. 7-Dehydrocholesterol reductase (DHCR) catalyzes the reduction of the Δ 7 double bond of sterols and is suspected to be defective in C. elegans, in which the major endogenous sterol is 7-dehydrocholesterol (7DHC). We microinjected a human DHCR expression vector into C. elegans, which was then incorporated into chromosome by γ-radiation. This transgenic C. elegans was named cholegans, i.e., cholesterol-producing C. elegans, because it was able to convert 7DHC into cholesterol. We investigated the effects of changes in sterol composition on longevity and stress resistance by examining brood size, mean life span, UV resistance, and thermotolerance. Cholegans contained 80% more cholesterol than the wild-type control. The brood size of cholegans was reduced by 40% compared to the wild-type control, although the growth rate was not significantly changed. The mean life span of cholegans was increased up to 131% in sterol-deficient medium as compared to wild-type. The biochemical basis for life span extension of cholegans appears to partly result from its acquired resistance against both UV irradiation and thermal stress

  10. Achieving secondary prevention low-density lipoprotein particle concentration goals using lipoprotein cholesterol-based data.

    Directory of Open Access Journals (Sweden)

    Simon C Mathews

    Full Text Available BACKGROUND: Epidemiologic studies suggest that LDL particle concentration (LDL-P may remain elevated at guideline recommended LDL cholesterol goals, representing a source of residual risk. We examined the following seven separate lipid parameters in achieving the LDL-P goal of <1000 nmol/L goal for very high risk secondary prevention: total cholesterol to HDL cholesterol ratio, TC/HDL, <3; a composite of ATP-III very high risk targets, LDL-C<70 mg/dL, non-HDL-C<100 mg/dL and TG<150 mg/dL; a composite of standard secondary risk targets, LDL-C<100, non-HDL-C<130, TG<150; LDL phenotype; HDL-C ≥ 40; TG<150; and TG/HDL-C<3. METHODS: We measured ApoB, ApoAI, ultracentrifugation lipoprotein cholesterol and NMR lipoprotein particle concentration in 148 unselected primary and secondary prevention patients. RESULTS: TC/HDL-C<3 effectively discriminated subjects by LDL-P goal (F = 84.1, p<10(-6. The ATP-III very high risk composite target (LDL-C<70, nonHDL-C<100, TG<150 was also effective (F = 42.8, p<10(-5. However, the standard secondary prevention composite (LDL-C<100, non-HDL-C<130, TG<150 was also effective but yielded higher LDL-P than the very high risk composite (F = 42.0, p<10(-5 with upper 95% confidence interval of LDL-P less than 1000 nmol/L. TG<150 and TG/HDL-C<3 cutpoints both significantly discriminated subjects but the LDL-P upper 95% confidence intervals fell above goal of 1000 nmol/L (F = 15.8, p = 0.0001 and F = 9.7, p = 0.002 respectively. LDL density phenotype neared significance (F = 2.85, p = 0.094 and the HDL-C cutpoint of 40 mg/dL did not discriminate (F = 0.53, p = 0.47 alone or add discriminatory power to ATP-III targets. CONCLUSIONS: A simple composite of ATP-III very high risk lipoprotein cholesterol based treatment targets or TC/HDL-C ratio <3 most effectively identified subjects meeting the secondary prevention target level of LDL-P<1000 nmol/L, providing a potential alternative to advanced lipid testing in many clinical

  11. Tongxinluo Prevents Endothelial Dysfunction Induced by Homocysteine Thiolactone In Vivo via Suppression of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2015-01-01

    Full Text Available Aim. To explore whether Chinese traditional medicine, tongxinluo (TXL, exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL and to investigate the potential mechanisms. Methods and Results. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM for 24 hours significantly reduced cell viabilities assayed by MTT, and enhanced productions of reactive oxygen species. Pretreatment of cells with TXL (100, 200, and 400 μg/mL for 1 hour reversed these effects induced by HTL. Further, coincubation with GW9662 (0.01, 0.1 mM abolished the protective effects of TXL on HTL-treated cells. In ex vivo experiments, exposure of isolated aortic rings from rats to HTL (1 mM for 1 hour dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced SOD activity, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with TXL (100, 200, and 400 μg/mL normalized the disorders induced by HTL. Importantly, all effects induced by TXL were reversed by GW9662. In vivo analysis indicated that the administration of TXL (1.0 g/kg/d remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed with HTL (50 mg/kg/d for 8 weeks. Conclusions. TXL improves endothelial functions in rats fed with HTL, which is related to PPARγ-dependent suppression of oxidative stress.

  12. Cholesterol is essential for mitosis progression and its deficiency induces polyploid cell formation

    International Nuclear Information System (INIS)

    Fernandez, Carlos; Lobo, Maria del Val T.; Gomez-Coronado, Diego; Lasuncion, Miguel A.

    2004-01-01

    As an essential component of mammalian cell membranes, cells require cholesterol for proliferation, which is either obtained from plasma lipoproteins or synthesized intracellularly from acetyl-CoA. In addition to cholesterol, other non-sterol mevalonate derivatives are necessary for DNA synthesis, such as the phosphorylated forms of isopentane, farnesol, geranylgeraniol, and dolichol. The aim of the present study was to elucidate the role of cholesterol in mitosis. For this, human leukemia cells (HL-60) were incubated in a cholesterol-free medium and treated with SKF 104976, which inhibits cholesterol biosynthesis by blocking sterol 14α-demethylase, and the expression of relevant cyclins in the different phases of the cell cycle was analyzed by flow cytometry. Prolonged cholesterol starvation induced the inhibition of cytokinesis and the formation of polyploid cells, which were multinucleated and had mitotic aberrations. Supplementing the medium with cholesterol completely abolished these effects, demonstrating they were specifically due to cholesterol deficiency. This is the first evidence that cholesterol is essential for mitosis completion and that, in the absence of cholesterol, the cells fail to undergo cytokinesis, entered G1 phase at higher DNA ploidy (tetraploidy), and then progressed through S (rereplication) into G2, generating polyploid cells

  13. Low-fat diet and regular, supervised physical exercise in patients with symptomatic coronary artery disease: reduction of stress-induced myocardial ischemia

    International Nuclear Information System (INIS)

    Schuler, G.; Schlierf, G.; Wirth, A.

    1988-01-01

    The effects of physical exercise and normalization of serum lipoproteins on stress-induced myocardial ischemia were studied in 18 patients with coronary artery disease, stable angina pectoris, and mild hypercholesterolemia (total serum cholesterol 242 +/- 32 mg/dl). These patients underwent a combined regimen of low-fat/low-cholesterol diet and regular, supervised physical exercise at high intensity for 12 months. At 1 year serum lipoproteins has been lowered to ideal levels (serum cholesterol 202 +/- 31 mg/dl, low-density lipoproteins 130 +/- 30 mg/dl, very low-density lipoproteins 22 +/- 15 mg/dl, serum triglycerides 105 [69 to 304] mg/dl) and physical work capacity was improved by 21% (p less than .01). No significant effect was noted on high-density lipoproteins, probably as a result of the low-fat/high-carbohydrate diet. Stress-induced myocardial ischemia, as assessed by thallium-201 scintigraphy, was decreased by 54% (p less than .05) despite higher myocardial oxygen consumption. Eighteen patients matched for age and severity of coronary artery disease served as a control group and ''usual medical care'' was rendered by their private physicians. No significant changes with respect to serum lipoproteins, physical work capacity, maximal rate-pressure product, or stress-induced myocardial ischemia were observed in this group. These data indicate that regular physical exercise at high intensity, lowered body weight, and normalization of serum lipoproteins may alleviate compromised myocardial perfusion during stress

  14. Clonidine blocks stress-induced craving in cocaine users.

    Science.gov (United States)

    Jobes, Michelle L; Ghitza, Udi E; Epstein, David H; Phillips, Karran A; Heishman, Stephen J; Preston, Kenzie L

    2011-11-01

    Reactivity to stressors and environmental cues, a putative cause of relapse in addiction, may be a useful target for relapse-prevention medication. In rodents, alpha-2 adrenergic agonists such as clonidine block stress-induced reinstatement of drug seeking, but not drug cue-induced reinstatement. The objective of this study is to test the effect of clonidine on stress- and cue-induced craving in human cocaine users. Healthy, non-treatment-seeking cocaine users (n = 59) were randomly assigned to three groups receiving clonidine 0, 0.1, or 0.2 mg orally under double-blind conditions. In a single test session, each participant received clonidine or placebo followed 3 h later by exposure to two pairs of standardized auditory-imagery scripts (neutral/stress and neutral/drug). Subjective measures of craving were collected. Subjective responsivity ("crave cocaine" Visual Analog Scale) to stress scripts was significantly attenuated in the 0.1- and 0.2-mg clonidine groups; for drug-cue scripts, this attenuation occurred only in the 0.2-mg group. Other subjective measures of craving showed similar patterns of effects but Dose × Script interactions were not significant. Clonidine was effective in reducing stress-induced (and, at a higher dose, cue-induced) craving in a pattern consistent with preclinical findings, although this was significant on only one of several measures. Our results, though modest and preliminary, converge with other evidence to suggest that alpha-2 adrenergic agonists may help prevent relapse in drug abusers experiencing stress or situations that remind them of drug use.

  15. Effects of disturbed liver growth and oxidative stress of high-fat diet-fed dams on cholesterol metabolism in offspring mice.

    Science.gov (United States)

    Kim, Juyoung; Kim, Juhae; Kwon, Young Hye

    2016-08-01

    Changes in nutritional status during gestation and lactation have detrimental effects on offspring metabolism. Several animal studies have shown that maternal high-fat diet (HFD) can predispose the offspring to development of obesity and metabolic diseases, however the mechanisms underlying these transgenerational effects are poorly understood. Therefore, we examined the effect of maternal HFD consumption on metabolic phenotype and hepatic expression of involved genes in dams to determine whether any of these parameters were associated with the metabolic outcomes in the offspring. Female C57BL/6 mice were fed a low-fat diet (LFD: 10% calories from fat) or a high-fat diet (HFD: 45% calories from fat) for three weeks before mating, and during pregnancy and lactation. Dams and their male offspring were studied at weaning. Dams fed an HFD had significantly higher body and adipose tissue weights and higher serum triglyceride and cholesterol levels than dams fed an LFD. Hepatic lipid levels and mRNA levels of genes involved in lipid metabolism, including LXRα, SREBP-2, FXR, LDLR, and ABCG8 were significantly changed by maternal HFD intake. Significantly lower total liver DNA and protein contents were observed in dams fed an HFD, implicating the disturbed liver adaptation in the pregnancy-related metabolic demand. HFD feeding also induced significant oxidative stress in serum and liver of dams. Offspring of dams fed an HFD had significantly higher serum cholesterol levels, which were negatively correlated with liver weights of dams and positively correlated with hepatic lipid peroxide levels in dams. Maternal HFD consumption induced metabolic dysfunction, including altered liver growth and oxidative stress in dams, which may contribute to the disturbed cholesterol homeostasis in the early life of male mice offspring.

  16. Camellia sinensis Prevents Perinatal Nicotine-Induced Neurobehavioral Alterations, Tissue Injury, and Oxidative Stress in Male and Female Mice Newborns

    Science.gov (United States)

    Ajarem, Jamaan S.; Al-Basher, Gadh; Allam, Ahmed A.

    2017-01-01

    Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea (Camellia sinensis) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15. Nicotine-exposed newborns showed significant delay in eye opening and hair appearance and declined body weight at birth and at D21. Nicotine induced neuromotor alterations in both male and female newborns evidenced by the suppressed righting, rotating, and cliff avoidance reflexes. Nicotine-exposed newborns exhibited declined memory, learning, and equilibrium capabilities, as well as marked anxiety behavior. C. sinensis significantly improved the physical development, neuromotor maturation, and behavioral performance in nicotine-exposed male and female newborns. In addition, C. sinensis prevented nicotine-induced tissue injury and lipid peroxidation and enhanced antioxidant defenses in the cerebellum and medulla oblongata of male and female newborns. In conclusion, this study shows that C. sinensis confers protective effects against perinatal nicotine-induced neurobehavioral alterations, tissue injury, and oxidative stress in mice newborns. PMID:28588748

  17. A milk-based wolfberry preparation prevents prenatal stress-induced cognitive impairment of offspring rats, and inhibits oxidative damage and mitochondrial dysfunction in vitro.

    Science.gov (United States)

    Feng, Zhihui; Jia, Haiqun; Li, Xuesen; Bai, Zhuanli; Liu, Zhongbo; Sun, Lijuan; Zhu, Zhongliang; Bucheli, Peter; Ballèvre, Olivier; Wang, Junkuan; Liu, Jiankang

    2010-05-01

    Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae. The red-colored fruits of L. barbarum have been used for a long time as an ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal medicine for improving health. However, its effects on cognitive function have not been well studied. In the present study, prevention of a milk-based wolfberry preparation (WP) on cognitive dysfunction was tested in a prenatal stress model with rats and the antioxidant mechanism was tested by in vitro experiments. We found that prenatal stress caused a significant decrease in cognitive function (Morris water maze test) in female offspring. Pretreatment of the mother rats with WP significantly prevented the prenatal stress-induced cognitive dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl and superoxide radicals (determined by an electron spin resonance spectrometric assay), and inhibited FeCl(2)/ascorbic acid-induced dysfunction in brain tissue and tissue mitochondria, including increases in reactive oxygen species and lipid peroxidation and decreases in the activities of complex I, complex II, and glutamate cysteine ligase. These results suggest that dietary supplementation with WP may be an effective strategy for preventing the brain oxidative mitochondrial damage and cognitive dysfunction associated with prenatal stress.

  18. Inhibitory action of conventional food-grade natural antioxidants and of natural antioxidants of new development on the thermal-induced oxidation of cholesterol.

    Science.gov (United States)

    Valenzuela, Alfonso; Sanhueza, Julio; Alonso, Pilar; Corbari, Alicia; Nieto, Susana

    2004-03-01

    Cholesterol is a molecule with an unsaturated bond; therefore, like polyunsaturated fatty acids, it is prone to oxidation. Cholesterol oxidation products (COPs) are found in many common foods and have been shown to be atherogenic, cytotoxic, mutagenic and possibly carcinogenic. Therefore, efforts to prevent or to avoid COPs formation during manufacture and/or processing of foods are of high priority. The effect of natural antioxidants on COPs formation has not been extensively studied. We assayed the effect of some widely applied natural antioxidants, such as tocopherol homologs (alpha-T, gamma-T, and delta-T) and rosemary extract, and of some natural products of newly developed as antioxidants, such as the flavonoids quercetin, catechin, morin, and rutin, and also of an alkaloid-derived product, boldine, to inhibit cholesterol oxidation of soybean oil, added of cholesterol, induced in the Rancimat test conditions (150 degrees C and air bubbling). Formation of six different COPs at the induction period and at the 100 microS conductivity value was monitored by gas chromatography. Under the experimental conditions gamma-T, quercetin, and rosemary extract prove effective to inhibit both soybean oil oxidation and COP formation. alpha-T, catechin, and morin are less efficient to prevent COP formation. delta-T, rutin and boldine are devoid of protective action against COP formation. gamma-T, quercetin and rosemary extract may inhibit COP formation from the nucleus and from the lateral chain of the cholesterol molecule.

  19. Histone deacetylase inhibition abolishes stress-induced spatial memory impairment.

    Science.gov (United States)

    Vargas-López, Viviana; Lamprea, Marisol R; Múnera, Alejandro

    2016-10-01

    Acute stress induced before spatial training impairs memory consolidation. Although non-epigenetic underpinning of such effect has been described, the epigenetic mechanisms involved have not yet been studied. Since spatial training and intense stress have opposite effects on histone acetylation balance, it is conceivable that disruption of such balance may underlie acute stress-induced spatial memory consolidation impairment and that inhibiting histone deacetylases prevents such effect. Trichostatin-A (TSA, a histone deacetylase inhibitor) was used to test its effectiveness in preventing stress' deleterious effect on memory. Male Wistar rats were trained in a spatial task in the Barnes maze; 1-h movement restraint was applied to half of them before training. Immediately after training, stressed and non-stressed animals were randomly assigned to receive either TSA (1mg/kg) or vehicle intraperitoneal injection. Twenty-four hours after training, long-term spatial memory was tested; plasma and brain tissue were collected immediately after the memory test to evaluate corticosterone levels and histone H3 acetylation in several brain areas. Stressed animals receiving vehicle displayed memory impairment, increased plasma corticosterone levels and markedly reduced histone H3 acetylation in prelimbic cortex and hippocampus. Such effects did not occur in stressed animals treated with TSA. The aforementioned results support the hypothesis that acute stress induced-memory impairment is related to histone deacetylation. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Perilla Oil Supplementation Ameliorates High-Fat/High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease in Rats via Enhanced Fecal Cholesterol and Bile Acid Excretion

    Directory of Open Access Journals (Sweden)

    Ting Chen

    2016-01-01

    Full Text Available Recent experimental studies and clinical trials have shown that hepatic cholesterol metabolic disorders are closely related to the development of nonalcoholic fatty liver disease (NAFLD. The main goal of this study was to investigate the efficacy of the perilla oil rich in alpha-linolenic acid (ALA against NASH and gain a deep insight into its potential mechanisms. Rats were fed a high-fat/high-cholesterol diet (HFD supplement with perilla oil (POH for 16 weeks. Routine blood biochemical tests and histological staining illustrated that the perilla oil administration improved HFD-induced hyperlipidemia, reduced hepatic steatosis, and inhibited hepatic inflammatory infiltration and fibrosis. Perilla oil also increased fecal bile acid and cholesterol excretion. Hepatic RNA-Seq analysis found that the long time perilla oil supplement notably modified the gene expression involved in cholesterol metabolism. Our results implicate that, after long-term high level dietary cholesterol feeding, rat liver endogenous synthesis of cholesterol and cholesterol-rich low density lipoprotein uptake was significantly inhibited, and perilla oil did not modulate expression of genes responsible for cholesterol synthesis but did increase cholesterol removed from hepatocytes by conversion to bile acids and increased fecal cholesterol excretion.

  1. Oral administration of γ-aminobutyric acid and γ-oryzanol prevents stress-induced hypoadiponectinemia.

    Science.gov (United States)

    Ohara, Kazuyuki; Kiyotani, Yuka; Uchida, Asako; Nagasaka, Reiko; Maehara, Hiroyuki; Kanemoto, Shigeharu; Hori, Masatoshi; Ushio, Hideki

    2011-06-15

    Metabolic syndrome is a cluster of risk factors including insulin resistance and type 2 diabetes and is found to associate partly with chronic stress at work in human. Adiponectin circulates in mammal blood mainly as a low molecular weight (LMW) trimer, hexamer, and a high molecular weight (HMW) multimers. Low circulating levels of adiponectin are related to metabolic syndrome. We have then investigated the influence of immobilization stress on plasma adiponectin concentrations in mice. Relative LMW and HMW adiponectin levels were markedly reduced by immobilization stress (0.66±0.07 and 0.59±0.06 after 102 h, respectively), significantly different from the control values (p-oryzanol abundantly contained in germinated brown rice have some physiological functions. We further investigated the effect of GABA, γ-oryzanol, GABA plus γ-oryzanol on adiponectin levels in mice subjected to immobilization stress. GABA and γ-oryzanol significantly increased the relative LMW and HMW adiponectin levels under immobilization stress (1.10±0.11 and 0.99±0.19 after 102 h, respectively, for GABA; 1.08±0.17 and 1.15±0.17 after 102 h, respectively, for γ-oryzanol). Additionally, the co-administration of GABA and γ-oryzanol also increased both relative LMW and HMW adiponectin levels (1.02±0.07 and 0.99±0.10 after 102 h, respectively) and was effective in an earlier phase from 30 to 54 h. The results indicate that the co-administration of GABA and γ-oryzanol might be effective in preventing stress-induced hypoadiponectinemia in mice and be also a promising tool for improving metabolic syndrome aggravated by chronic stress. Copyright © 2011 Elsevier GmbH. All rights reserved.

  2. Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

    Science.gov (United States)

    Roy, Abhro Jyoti; Stanely Mainzen Prince, P

    2013-10-01

    The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Araloside C Prevents Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress via Increasing Heat Shock Protein 90 in H9c2 Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Yuyang Du

    2018-04-01

    Full Text Available Araloside C (AsC is a cardioprotective triterpenoid compound that is mainly isolated from Aralia elata. This study aims to determine the effects of AsC on hypoxia-reoxygenation (H/R-induced apoptosis in H9c2 cardiomyocytes and its underlying mechanisms. Results demonstrated that pretreatment with AsC (12.5 μM for 12 h significantly suppressed the H/R injury in H9c2 cardiomyocytes, including improving cell viability, attenuating the LDH leakage and preventing cardiomyocyte apoptosis. AsC also inhibited H/R-induced ER stress by reducing the activation of ER stress pathways (PERK/eIF2α and ATF6, and decreasing the expression of ER stress-related apoptotic proteins (CHOP and caspase-12. Moreover, AsC greatly improved the expression level of HSP90 compared with that in the H/R group. The use of HSP90 inhibitor 17-AAG and HSP90 siRNA blocked the above suppression effect of AsC on ER stress-related apoptosis caused by H/R. Taken together, AsC could reduce H/R-induced apoptosis possibly because it attenuates ER stress-dependent apoptotic pathways by increasing HSP90 expression.

  4. Myricetin protects against diet-induced obesity and ameliorates oxidative stress in C57BL/6 mice.

    Science.gov (United States)

    Su, Hong-Ming; Feng, Li-Na; Zheng, Xiao-Dong; Chen, Wei

    2016-06-01

    Myricetin is a naturally occurring antioxidant commonly found in various plants. However, little information is available with respect to its direct anti-obesity effects. This study was undertaken to investigate the effect of myricetin on high-fat diet (HFD)-induced obesity in C57BL/6 mice. Administration of myricetin dramatically reduced the body weight of diet-induced obese mice compared with solely HFD-induced mice. Several parameters related to obesity including serum glucose, triglyceride, and cholesterol were significantly decreased in myricetin-treated mice. Moreover, obesity-associated oxidative stress (glutathione peroxidase (GPX) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA)) and inflammation (tumor necrosis factor-α (TNF-α)) were ameliorated in myricetin-treated mice. Further investigation revealed that the protective effect of myricetin against HFD-induced obesity in mice appeared to be partially mediated through the down-regulation of mRNA expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and lipogenic transcription factor sterol regulatory element-binding protein 1c (SREBP-1c). Consumption of myricetin may help to prevent obesity and obesity-related metabolic complications.

  5. Defensive effect of lansoprazole in dementia of AD type in mice exposed to streptozotocin and cholesterol enriched diet.

    Science.gov (United States)

    Sodhi, Rupinder K; Singh, Nirmal

    2013-01-01

    The present study investigates the potential of lansoprazole (a proton pump inhibitor and agonist of liver x receptors) in experimental dementia of AD type. Streptozotocin [STZ, 3 mg/kg, injected intracerebroventricular (i.c.v), and high fat diet (HFD, administered for 90 days)] were used to induce dementia in separate groups of Swiss mice. Morris water maze (MWM) test was performed to assess learning and memory of the animals. A battery of biochemical and histopathological studies were also performed. Extent of oxidative stress was measured by estimating the levels of brain reduced glutathione (GSH) and thiobarbituric acid reactive species (TBARS). Brain acetylcholinestrase (AChE) activity and serum cholesterol levels were also estimated. The brain level of myeloperoxidase (MPO) was measured as a marker of inflammation. STZ and HFD produced a marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ/HFD treated mice exhibited a marked accentuation of AChE activity, TBARS and MPO levels along with a fall in GSH levels. Further, the stained micrographs of STZ/HFD treated mice indicated pathological changes, severe neutrophilic infiltration and amyloid deposition. Lansoprazole treatment significantly attenuated STZ and HFD -induced memory deficits, biochemical and histopathological alterations. It also prevented HFD-induced rise in the cholesterol level. Therefore, the findings demonstrate potential of lansoprazole in memory dysfunctions which may probably be attributed to its anti-cholinesterase, anti-oxidative and anti-inflammatory effects. Moreover, both cholesterol-dependent as well as cholesterol-independent effects of lansoprazole appear to play a role. In addition study indicates the role of liver x receptors in dementia.

  6. High Cholesterol/Low Cholesterol: Effects in Biological Membranes: A Review.

    Science.gov (United States)

    Subczynski, Witold K; Pasenkiewicz-Gierula, Marta; Widomska, Justyna; Mainali, Laxman; Raguz, Marija

    2017-12-01

    Lipid composition determines membrane properties, and cholesterol plays a major role in this determination as it regulates membrane fluidity and permeability, as well as induces the formation of coexisting phases and domains in the membrane. Biological membranes display a very diverse lipid composition, the lateral organization of which plays a crucial role in regulating a variety of membrane functions. We hypothesize that, during biological evolution, membranes with a particular cholesterol content were selected to perform certain functions in the cells of eukaryotic organisms. In this review, we discuss the major membrane properties induced by cholesterol, and their relationship to certain membrane functions.

  7. Functional foods for the prevention and treatment of cardiovascular diseases: cholesterol and beyond.

    Science.gov (United States)

    Rudkowska, Iwona; Jones, Peter J H

    2007-05-01

    Cardiovascular disease (CVD) is a major cause of death and disability in many developed countries. The purpose of this literature review is to establish a recommendation for the intake of functional food ingredients in a healthy diet--such as plant sterols (PSs) in low-fat and functional matrices, fatty acid composition and other nutrients of tree nuts and flavonoids in dark chocolate--for the prevention and treatment of CVD. These three specific functional foods are explored in this review, since there is a higher potential for their increased consumption by the population to prevent CVD. First, PS have been added to various nontraditional matrices, such as low-fat products and functional oils, which have shown cholesterol-lowering effects in most clinical trials. Secondly, a growing number of clinical studies indicate that the beneficial effect of tree nuts may not only be due to their fatty acid composition but to other key nutrients, which may provide supplementary health benefits, such as endothelial cell function, as well as decreasing total cholesterol and low-density lipoprotein cholesterol (LDL-C). Lastly, flavonoids in dark chocolate may protect LDL-C particles from undergoing oxidative modification. However, some gaps in our knowledge need to be filled before firm recommendations can be made for habitual dark chocolate consumption. Overall, these functional foods should be considered as an addition to current lipid-lowering recommendations for improving CVD risk.

  8. Stress Prevention@Work: a study protocol for the evaluation of a multifaceted integral stress prevention strategy to prevent employee stress in a healthcare organization: a cluster controlled trial.

    Science.gov (United States)

    Hoek, Rianne J A; Havermans, Bo M; Houtman, Irene L D; Brouwers, Evelien P M; Heerkens, Yvonne F; Zijlstra-Vlasveld, Moniek C; Anema, Johannes R; van der Beek, Allard J; Boot, Cécile R L

    2017-07-17

    Adequate implementation of work-related stress management interventions can reduce or prevent work-related stress and sick leave in organizations. We developed a multifaceted integral stress-prevention strategy for organizations from several sectors that includes a digital platform and collaborative learning network. The digital platform contains a stepwise protocol to implement work-related stress-management interventions. It includes stress screeners, interventions and intervention providers to facilitate access to and the selection of matching work-related stress-management interventions. The collaborative learning network, including stakeholders from various organizations, plans meetings focussing on an exchange of experiences and good practices among organizations for the implementation of stress prevention measures. This paper describes the design of an integral stress-prevention strategy, Stress Prevention@Work, and the protocol for the evaluation of: 1) the effects of the strategy on perceived stress and work-related outcomes, and 2) the barriers and facilitators for implementation of the strategy. The effectiveness of Stress Prevention@Work will be evaluated in a cluster controlled trial, in a large healthcare organization in the Netherlands, at six and 12 months. An independent researcher will match teams on working conditions and size and allocate the teams to the intervention or control group. Teams in the intervention group will be offered Stress Prevention@Work. For each intervention team, one employee is responsible for applying the strategy within his/her team using the digital platform and visiting the collaborative learning network. Using a waiting list design, the control group will be given access to the strategy after 12 months. The primary outcome is the employees' perceived stress measured by the stress subscale of the Depression, Anxiety, and Stress Scale (DASS-21). Secondary outcome measures are job demands, job resources and the number

  9. N-acetyl-L-cysteine prevents stress-induced desmin aggregation in cellular models of desminopathy.

    Directory of Open Access Journals (Sweden)

    Bertrand-David Segard

    Full Text Available Mutations within the human desmin gene are responsible for a subcategory of myofibrillar myopathies called desminopathies. However, a single inherited mutation can produce different phenotypes within a family, suggesting that environmental factors influence disease states. Although several mouse models have been used to investigate organ-specific desminopathies, a more general mechanistic perspective is required to advance our knowledge toward patient treatment. To improve our understanding of disease pathology, we have developed cellular models to observe desmin behaviour in early stages of disease pathology, e.g., upon formation of cytoplasmic desmin aggregates, within an isogenic background. We cloned the wildtype and three mutant desmin cDNAs using a Tet-On Advanced® expression system in C2C12 cells. Mutations were selected based on positioning within desmin and capacity to form aggregates in transient experiments, as follows: DesS46Y (head domain; low aggregation, DesD399Y (central rod domain; high aggregation, and DesS460I (tail domain; moderate aggregation. Introduction of these proteins into a C2C12 background permitted us to compare between desmin variants as well as to determine the role of external stress on aggregation. Three different types of stress, likely encountered during muscle activity, were introduced to the cell models-thermal (heat shock, redox-associated (H2O2 and cadmium chloride, and mechanical (stretching stresses-after which aggregation was measured. Cells containing variant DesD399Y were more sensitive to stress, leading to marked cytoplasmic perinuclear aggregations. We then evaluated the capacity of biochemical compounds to prevent this aggregation, applying dexamethasone (an inducer of heat shock proteins, fisetin or N-acetyl-L-cysteine (antioxidants before stress induction. Interestingly, N-acetyl-L-cysteine pre-treatment prevented DesD399Y aggregation during most stress. N-acetyl-L-cysteine has recently been

  10. Water stress induces overexpression of superoxide dismutases that ...

    African Journals Online (AJOL)

    Water stress is known to induce active oxygen species in plants. The accumulation of these harmful species must be prevented by plants as rapidly as possible to maintain growth and productivity. The aim of this study was to determine the effect of water stress on superoxide dismutase isozymes (SOD, EC 1.15.1.1.) in two ...

  11. Stress Prevention@Work: a study protocol for the evaluation of a multifaceted integral stress prevention strategy to prevent employee stress in a healthcare organization: a cluster controlled trial

    Directory of Open Access Journals (Sweden)

    Rianne J. A. Hoek

    2017-07-01

    Full Text Available Abstract Background Adequate implementation of work-related stress management interventions can reduce or prevent work-related stress and sick leave in organizations. We developed a multifaceted integral stress-prevention strategy for organizations from several sectors that includes a digital platform and collaborative learning network. The digital platform contains a stepwise protocol to implement work-related stress-management interventions. It includes stress screeners, interventions and intervention providers to facilitate access to and the selection of matching work-related stress-management interventions. The collaborative learning network, including stakeholders from various organizations, plans meetings focussing on an exchange of experiences and good practices among organizations for the implementation of stress prevention measures. This paper describes the design of an integral stress-prevention strategy, Stress Prevention@Work, and the protocol for the evaluation of: 1 the effects of the strategy on perceived stress and work-related outcomes, and 2 the barriers and facilitators for implementation of the strategy. Methods The effectiveness of Stress Prevention@Work will be evaluated in a cluster controlled trial, in a large healthcare organization in the Netherlands, at six and 12 months. An independent researcher will match teams on working conditions and size and allocate the teams to the intervention or control group. Teams in the intervention group will be offered Stress Prevention@Work. For each intervention team, one employee is responsible for applying the strategy within his/her team using the digital platform and visiting the collaborative learning network. Using a waiting list design, the control group will be given access to the strategy after 12 months. The primary outcome is the employees’ perceived stress measured by the stress subscale of the Depression, Anxiety, and Stress Scale (DASS-21. Secondary outcome measures

  12. Ursolic acid protects monocytes against metabolic stress-induced priming and dysfunction by preventing the induction of Nox4

    Directory of Open Access Journals (Sweden)

    Sarah L. Ullevig

    2014-01-01

    Conclusion: UA protects THP-1 monocytes against dysfunction by suppressing metabolic stress-induced Nox4 expression, thereby preventing the Nox4-dependent dysregulation of redox-sensitive processes, including actin turnover and MAPK-signaling, two key processes that control monocyte migration and adhesion. This study provides a novel mechanism for the anti-inflammatory and athero- and renoprotective properties of UA and suggests that dysfunctional blood monocytes may be primary targets of UA and related compounds.

  13. Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Minglong Shao

    Full Text Available Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR plays a critical role in attenuating insulin resistance, inflammation and oxidative stress.The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms.Mice were fed with a high-fat diet (HFD, 40% of calories from fat for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured.HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2 expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks.These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.

  14. Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat.

    Science.gov (United States)

    Fujikawa, Takahiko; Soya, Hideaki; Tamashiro, Kellie L K; Sakai, Randall R; McEwen, Bruce S; Nakai, Naoya; Ogata, Masato; Suzuki, Ikukatsu; Nakashima, Kunio

    2004-04-01

    Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. We also show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

  15. Alpinumisoflavone and abyssinone V 4'-methylether derived from Erythrina lysistemon (Fabaceae) promote HDL-cholesterol synthesis and prevent cholesterol gallstone formation in ovariectomized rats.

    Science.gov (United States)

    Mvondo, Marie A; Njamen, Dieudonné; Kretzschmar, Georg; Imma Bader, Manuela; Tanee Fomum, Stephen; Wandji, Jean; Vollmer, Günter

    2015-07-01

    Erythrina lysistemon was found to improve lipid profile in ovariectomized rats. Alpinumisoflavone (AIF) and abyssinone V 4'-methylether (AME) derived from this plant induced analogous effects on lipid profile and decreased atherogenic risks. To highlight the molecular mechanism of action of these natural products, we evaluated their effects on the expression of some estrogen-sensitive genes associated with cholesterol synthesis (Esr1 and Apoa1) and cholesterol clearance (Ldlr, Scarb1 and Cyp7a1). Ovariectomized rats were subcutaneously treated for three consecutive days with either compound at the daily dose of 0.1, 1 and 10 mg/kg body weight (BW). Animals were sacrificed thereafter and their liver was collected. The mRNA of genes of interest was analysed by quantitative real-time polymerase chain reaction. Both compounds downregulated the mRNA expression of Esr1, a gene associated with cholesterogenesis and cholesterol gallstone formation. AME leaned the Apoa1/Scarb1 balance in favour of Apoa1, an effect promoting high-density lipoprotein (HDL)-cholesterol formation. It also upregulated the mRNA expression of Ldlr at 1 mg/kg/BW per day (25%) and 10 mg/kg/BW per day (133.17%), an effect favouring the clearance of low-density lipoprotein (LDL)-cholesterol. Both compounds may also promote the conversion of cholesterol into bile acids as they upregulated Cyp7a1 mRNA expression. AIF and AME atheroprotective effects may result from their ability to upregulate mechanisms promoting HDL-cholesterol and bile acid formation. © 2015 Royal Pharmaceutical Society.

  16. Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Janis Ya-Xian Zhan

    2016-01-01

    Full Text Available Andrographolide sodium bisulfate (ASB, a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti-inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1β, IL-6, IL-10, and TNF-α in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent.

  17. Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation

    Science.gov (United States)

    Zhan, Janis Ya-Xian; Wang, Xiu-Fen; Liu, Yu-Hong; Zhang, Zhen-Biao; Wang, Lan; Chen, Jian-Nan; Huang, Song; Zeng, Hui-Fang; Lai, Xiao-Ping

    2016-01-01

    Andrographolide sodium bisulfate (ASB), a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti-inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV) irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1β, IL-6, IL-10, and TNF-α in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent. PMID:26903706

  18. Isoflavone and Protein Constituents of Lactic Acid-Fermented Soy Milk Combine to Prevent Dyslipidemia in Rats Fed a High Cholesterol Diet

    OpenAIRE

    Kobayashi, Maki; Egusa, Shintaro; Fukuda, Mitsuru

    2014-01-01

    A high cholesterol diet induces dyslipidemia. This study investigated whether isoflavone aglycones in lactic acid-fermented soy milk (LFS) improve lipid metabolism in rats fed a high cholesterol diet. Male Sprague-Dawley rats aged seven weeks were fed an AIN-93G diet, a 1% cholesterol diet (a high cholesterol diet), a high-cholesterol diet containing 4% isoflavone extract of LFS (LFS extract diet), a high-cholesterol diet containing 19.4% ethanol-washed LFS (ethanol-washed LFS diet, isoflavon...

  19. Sensitivity to lysosome-dependent cell death is directly regulated by lysosomal cholesterol content.

    Directory of Open Access Journals (Sweden)

    Hanna Appelqvist

    Full Text Available Alterations in lipid homeostasis are implicated in several neurodegenerative diseases, although the mechanisms responsible are poorly understood. We evaluated the impact of cholesterol accumulation, induced by U18666A, quinacrine or mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1 protein, on lysosomal stability and sensitivity to lysosome-mediated cell death. We found that neurons with lysosomal cholesterol accumulation were protected from oxidative stress-induced apoptosis. In addition, human fibroblasts with cholesterol-loaded lysosomes showed higher lysosomal membrane stability than controls. Previous studies have shown that cholesterol accumulation is accompanied by the storage of lipids such as sphingomyelin, glycosphingolipids and sphingosine and an up regulation of lysosomal associated membrane protein-2 (LAMP-2, which may also influence lysosomal stability. However, in this study the use of myriocin and LAMP deficient fibroblasts excluded these factors as responsible for the rescuing effect and instead suggested that primarily lysosomal cholesterol content determineD the cellular sensitivity to toxic insults. Further strengthening this concept, depletion of cholesterol using methyl-β-cyclodextrin or 25-hydroxycholesterol decreased the stability of lysosomes and cells became more prone to undergo apoptosis. In conclusion, cholesterol content regulated lysosomal membrane permeabilization and thereby influenced cell death sensitivity. Our data suggests that lysosomal cholesterol modulation might be used as a therapeutic strategy for conditions associated with accelerated or repressed apoptosis.

  20. Diabetic Cardiovascular Disease Induced by Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yosuke Kayama

    2015-10-01

    Full Text Available Cardiovascular disease (CVD is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM. DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD, cardiac hypertrophy, and heart failure (HF. HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS. ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.

  1. Haptoglobin is required to prevent oxidative stress and muscle atrophy.

    Directory of Open Access Journals (Sweden)

    Enrico Bertaggia

    Full Text Available BACKGROUND: Oxidative stress (OS plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function. Hp is induced in pro-oxidative conditions such as systemic inflammation or obesity. The role of systemic factors that modulate oxidative stress inside muscle cells is still poorly investigated. RESULTS: We used Hp knockout mice (Hp-/- to determine the role of this protein and therefore, of systemic OS in maintenance of muscle mass and function. Absence of Hp caused muscle atrophy and weakness due to activation of an atrophy program. When animals were stressed by acute exercise or by high fat diet (HFD, OS, muscle atrophy and force drop were exacerbated in Hp-/-. Depending from the stress condition, autophagy-lysosome and ubiquitin-proteasome systems were differently induced. CONCLUSIONS: Hp is required to prevent OS and the activation of pathways leading to muscle atrophy and weakness in normal condition and upon metabolic challenges.

  2. Effects of Uric Acid on Exercise-induced Oxidative Stress

    OpenAIRE

    平井, 富弘

    2001-01-01

    We studied effects of uric acid on exercise― induced oxidative stress in humans based on a hypothesis that uric acid acts as an antioxidant to prevent from exercise―induced oxidative stress. Relation between uric acid level in plasma and increase of thiobarbituric acid reactive substance (TBARS)after the cycle ergometer exercise was examined. Thiobarbituricacid reactive substance in plasma increased after the ergometer exercise. High uric acid in plasma did not result in low increase of TBARS...

  3. Functional role of CCCTC binding factor (CTCF) in stress-induced apoptosis

    International Nuclear Information System (INIS)

    Li Tie; Lu Luo

    2007-01-01

    CTCF, a nuclear transcriptional factor, is a multifunctional protein and involves regulation of growth factor- and cytokine-induced cell proliferation/differentiation. In the present study, we investigated the role of CTCF in protecting stress-induced apoptosis in various human cell types. We found that UV irradiation and hyper-osmotic stress induced human corneal epithelial (HCE) and hematopoietic myeloid cell apoptosis detected by significantly increased caspase 3 activity and decreased cell viability. The stress-induced apoptotic response in these cells requires down-regulation of CTCF at both mRNA and protein levels, suggesting that CTCF may play an important role in downstream events of stress-induced signaling pathways. Inhibition of NFκB activity prevented stress-induced down-regulation of CTCF and increased cell viability against stress-induced apoptosis. The anti-apoptotic effect of CTCF was further studied by manipulating CTCF activities in HCE and hematopoietic cells. Transient transfection of cDNAs encoding full-length human CTCF markedly suppressed stress-induced apoptosis in these cells. In contrast, knocking down of CTCF mRNA using siRNA specific to CTCF significantly promoted stress-induced apoptosis. Thus, our results reveal that CTCF is a down stream target of stress-induced signaling cascades and it plays a significant anti-apoptotic role in regulation of stress-induced cellular responses in HCE and hematopoietic myeloid cells

  4. 5,7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats through increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels

    Directory of Open Access Journals (Sweden)

    Wei Yang

    2018-02-01

    Full Text Available The current study was aimed to investigate the role of 5,7-dimethoxycoumarin in the prevention of chronic mild stress induced depression in rats. The chronic mild stress rat model was prepared using the known protocols. The results from open-field test showed that rats in the chronic mild stress group scored very low in terms of crossings and rearings than those of the normal rats. However, pre-treatment of the rats with 10 mg/kg doses of 5,7-dimethoxycoumarin prevented decline in the locomotor activity by chronic mild stress. The level of monoamine oxidase-A in the chronic mild stress rat hippocampus was markedly higher. Chronic mild stress induced increase in the monoamine oxidase-A level was inhibited by pre-treatment with 10 mg/kg doses of 5,7-dimethoxycoumarin in the rats. Chronic mild stress caused a marked increase in the level of caspase-3 mRNA and proteins in rat hippocampus tissues. The increased level of caspase-3 mRNA and protein level was inhibited by treatment of rats with 5,7-dimethoxycoumarin (10 mg/kg. 5,7-Dimethoxycoumarin administration into the rats caused a marked increase in the levels of heat shock protein-70 mRNA and protein. The levels of heat shock protein-70 were markedly lower both in normal and chronic mild stress groups of rats compared to the 5,7-dimethoxycoumarin treated groups. Thus 5,7-dimethoxycoumarin prevented the chronic mild stress induced depression in rats through an increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

  5. 5,7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats through increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

    Science.gov (United States)

    Yang, Wei; Wang, Huanlin

    2018-02-01

    The current study was aimed to investigate the role of 5,7-dimethoxycoumarin in the prevention of chronic mild stress induced depression in rats. The chronic mild stress rat model was prepared using the known protocols. The results from open-field test showed that rats in the chronic mild stress group scored very low in terms of crossings and rearings than those of the normal rats. However, pre-treatment of the rats with 10 mg/kg doses of 5,7-dimethoxycoumarin prevented decline in the locomotor activity by chronic mild stress. The level of monoamine oxidase-A in the chronic mild stress rat hippocampus was markedly higher. Chronic mild stress induced increase in the monoamine oxidase-A level was inhibited by pre-treatment with 10 mg/kg doses of 5,7-dimethoxycoumarin in the rats. Chronic mild stress caused a marked increase in the level of caspase-3 mRNA and proteins in rat hippocampus tissues. The increased level of caspase-3 mRNA and protein level was inhibited by treatment of rats with 5,7-dimethoxycoumarin (10 mg/kg). 5,7-Dimethoxycoumarin administration into the rats caused a marked increase in the levels of heat shock protein-70 mRNA and protein. The levels of heat shock protein-70 were markedly lower both in normal and chronic mild stress groups of rats compared to the 5,7-dimethoxycoumarin treated groups. Thus 5,7-dimethoxycoumarin prevented the chronic mild stress induced depression in rats through an increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

  6. 27-Oxygenated cholesterol induces expression of CXCL8 in macrophages via NF-κB and CD88

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun-Mi, E-mail: lala1647@hanmail.net [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Lee, Chung Won, E-mail: vasculardoctorlee@gmail.com [Department of Thoracic and Cardiovascular Surgery, Pusan National University Hospital, Pusan 602-739 (Korea, Republic of); Kim, Bo-Young, E-mail: kimboyoung@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Jung, Young-Suk, E-mail: youngjung@pusan.ac.kr [College of Pharmacy, Pusan National University, Busan 609-735 (Korea, Republic of); Eo, Seong-Kug, E-mail: vetvirus@chonbuk.ac.kr [College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan, Jeonbuk 570-752 (Korea, Republic of); Park, Young Chul, E-mail: ycpark@pusan.ac.kr [Department of Microbiology & Immunology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Kim, Koanhoi, E-mail: koanhoi@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of)

    2015-08-07

    We attempted to determine the effects of a milieu rich in cholesterol molecules on expression of chemokine CXCL8. A high-cholesterol diet led to an increased transcription of the IL-8 gene in the arteries and elevated levels of CXCL8 in sera of ApoE{sup −/−} mice, compared with those of wild-type C57BL/6 mice. Treatment of THP-1 monocyte/macrophage cells with 27-hydroxycholesterol (27OHChol) resulted in transcription of the IL-8 gene and increased secretion of its corresponding gene product whereas cholesterol did not induce expression of CXCL8 in THP-1 cells. 27OHChol-induced transcription of the IL-8 gene was blocked by cycloheximide, but not by polymyxin B. Treatment of THP-1 cells with 27OHChol caused translocation of p65 NF-κB subunit into the nucleus and up-regulation of CD88. Inhibition of NF-κB and CD88 using SN50 and W-54011, respectively, resulted in reduced transcription of the IL-8 gene and attenuated secretion of CXCL8 induced by 27OHChol. We propose that oxidatively modified cholesterol like 27OHChol, rather than cholesterol, is responsible for sustained expression of CXCL8 in monocytes/macrophages in atherosclerotic arteries. - Highlights: • Consumption of a high-cholesterol diet leads to increased CXCL8 expression in ApoE{sup −/−} mice. • 27OHChol, but not cholesterol, up-regulates expression of CXCL8 in macrophages. • 27OHChol enhances nuclear translocation of NF-κB and expression of CD88 in macrophages. • Inhibition of NF-κB or CD88 results in decreased CXCL8 expression induced by 27OHChol. • 27OHChol up-regulates CXCL8 expression via NF-κB and CD88 in macrophages.

  7. Defensive effect of lansoprazole in dementia of AD type in mice exposed to streptozotocin and cholesterol enriched diet.

    Directory of Open Access Journals (Sweden)

    Rupinder K Sodhi

    Full Text Available The present study investigates the potential of lansoprazole (a proton pump inhibitor and agonist of liver x receptors in experimental dementia of AD type. Streptozotocin [STZ, 3 mg/kg, injected intracerebroventricular (i.c.v, and high fat diet (HFD, administered for 90 days] were used to induce dementia in separate groups of Swiss mice. Morris water maze (MWM test was performed to assess learning and memory of the animals. A battery of biochemical and histopathological studies were also performed. Extent of oxidative stress was measured by estimating the levels of brain reduced glutathione (GSH and thiobarbituric acid reactive species (TBARS. Brain acetylcholinestrase (AChE activity and serum cholesterol levels were also estimated. The brain level of myeloperoxidase (MPO was measured as a marker of inflammation. STZ and HFD produced a marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ/HFD treated mice exhibited a marked accentuation of AChE activity, TBARS and MPO levels along with a fall in GSH levels. Further, the stained micrographs of STZ/HFD treated mice indicated pathological changes, severe neutrophilic infiltration and amyloid deposition. Lansoprazole treatment significantly attenuated STZ and HFD -induced memory deficits, biochemical and histopathological alterations. It also prevented HFD-induced rise in the cholesterol level. Therefore, the findings demonstrate potential of lansoprazole in memory dysfunctions which may probably be attributed to its anti-cholinesterase, anti-oxidative and anti-inflammatory effects. Moreover, both cholesterol-dependent as well as cholesterol-independent effects of lansoprazole appear to play a role. In addition study indicates the role of liver x receptors in dementia.

  8. Treatment and Prevention of Breast Cancer Using Multifunctional Inhibitors of Cholesterol Biosynthesis

    Science.gov (United States)

    2015-08-01

    suggesting an allosteric modification of estrogen receptor  RO blocks the production of an estrogen regulated gene ( progesterone receptor) in...alternative targets in the pathway leading to the production of cholesterol, which might be regulated with less toxic inhibitors to control the progression of...to effectively treat and prevent cancers of the breast. Our goal was to identify alternative targets in the pathway leading to the production of

  9. Modulation of Hypercholesterolemia-Induced Oxidative/Nitrative Stress in the Heart

    Science.gov (United States)

    Sárközy, Márta; Pipicz, Márton; Dux, László; Csont, Tamás

    2016-01-01

    Hypercholesterolemia is a frequent metabolic disorder associated with increased risk for cardiovascular morbidity and mortality. In addition to its well-known proatherogenic effect, hypercholesterolemia may exert direct effects on the myocardium resulting in contractile dysfunction, aggravated ischemia/reperfusion injury, and diminished stress adaptation. Both preclinical and clinical studies suggested that elevated oxidative and/or nitrative stress plays a key role in cardiac complications induced by hypercholesterolemia. Therefore, modulation of hypercholesterolemia-induced myocardial oxidative/nitrative stress is a feasible approach to prevent or treat deleterious cardiac consequences. In this review, we discuss the effects of various pharmaceuticals, nutraceuticals, some novel potential pharmacological approaches, and physical exercise on hypercholesterolemia-induced oxidative/nitrative stress and subsequent cardiac dysfunction as well as impaired ischemic stress adaptation of the heart in hypercholesterolemia. PMID:26788247

  10. Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

    Science.gov (United States)

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

  11. Cardio protective role of garlic (Allium Sativum) against oxidative stress induced by gamma radiation exposure

    International Nuclear Information System (INIS)

    Said, U.Z.; Azab, KH.SH.; And Soliman, A.M.

    2004-01-01

    Oxidative stress and free radicals play a crucial role in the pathophysiology of a broad spectrum of cardiovascular diseases. The need to identify agents with a potential for preventing such damage has assumed great importance. Therefore, the present study was designed to investigate the possible effect of raw garlic homogenate on cardiac endogenous antioxidants, lipid peroxidation and histopathological changes. Plasma lipid profile was also determined. Three different dosage levels (125, 250 and 500 mg/kg body weight) once daily for 20 days were evaluated. The results obtained showed that whole body gamma irradiation of rats at 6 Gy (single dose) resulted in significant increase in cardiac thiobarbituric acid reactive substances (TEARS) along with reduction in cardiac superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities 1, 2 and 4 weeks following radiation exposure. These changes were associated with subendocardial loss of muscles and accumulation of acute inflammatory cells surrounded by edema. Depletion of cardiac endogenous antioxidants and rise in TEARS were significantly less in the garlic treated rats. Also, histological examination of cardiac tissue showed less damage. Garlic treatment significantly diminished the radiation induced increase in the plasma content of triglycerides, total cholesterol and low density lipoprotein-cholesterol (LDL-C). Significant amelioration was also observed in the plasma content of high density lipoprotein- cholesterol (HDL-C) as compared to irradiated rats. Among the three garlic treated groups, 250 mg/kg group showed the best protection in terms of biochemical and histopathological evidences. It could be concluded that the intake dose plays an important role on endogenous antioxidants and cytoprotective effects on the heart

  12. SIRT7 Represses Myc Activity to Suppress ER Stress and Prevent Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Jiyung Shin

    2013-11-01

    Full Text Available Nonalcoholic fatty liver disease is the most common chronic liver disorder in developed countries. Its pathogenesis is poorly understood, and therapeutic options are limited. Here, we show that SIRT7, an NAD+-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress and prevent the development of fatty liver disease. SIRT7 is induced upon ER stress and is stabilized at the promoters of ribosomal proteins through its interaction with the transcription factor Myc to silence gene expression and to relieve ER stress. SIRT7-deficient mice develop chronic hepatosteatosis resembling human fatty liver disease. Myc inactivation or pharmacological suppression of ER stress alleviates fatty liver caused by SIRT7 deficiency. Importantly, SIRT7 suppresses ER stress and reverts the fatty liver disease in diet-induced obese mice. Our study identifies SIRT7 as a cofactor of Myc for transcriptional repression and delineates a druggable regulatory branch of the ER stress response that prevents and reverts fatty liver disease.

  13. Macrophage mitochondrial damage from StAR transport of 7-hydroperoxycholesterol: implications for oxidative stress-impaired reverse cholesterol transport.

    Science.gov (United States)

    Korytowski, Witold; Wawak, Katarzyna; Pabisz, Pawel; Schmitt, Jared C; Girotti, Albert W

    2014-01-03

    StAR family proteins in vascular macrophages participate in reverse cholesterol transport (RCT). We hypothesize that under pathophysiological oxidative stress, StARs will transport not only cholesterol to macrophage mitochondria, but also pro-oxidant cholesterol hydroperoxides (7-OOHs), thereby impairing early-stage RCT. Upon stimulation with dibutyryl-cAMP, RAW264.7 macrophages exhibited a strong time-dependent induction of mitochondrial StarD1 and plasma membrane ABCA1, which exports cholesterol. 7α-OOH uptake by stimulated RAW cell mitochondria (like cholesterol uptake) was strongly reduced by StarD1 knockdown, consistent with StarD1 involvement. Upon uptake by mitochondria, 7α-OOH (but not redox-inactive 7α-OH) triggered lipid peroxidation and membrane depolarization while reducing ABCA1 upregulation. These findings provide strong initial support for our hypothesis. Copyright © 2013. Published by Elsevier B.V.

  14. Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats.

    Directory of Open Access Journals (Sweden)

    Sarawut Lapmanee

    Full Text Available Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT, forced swimming test (FST, and Morris water maze (MWM. Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment.

  15. Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Sang; Lee, Hae-June; Lee, Yoon-Jin [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Jeong, Jae-Hoon [Division of Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Kang, Seongman [Division of Life Sciences, Korea University, Seoul 136-701 (Korea, Republic of); Lim, Young-Bin, E-mail: yblim@kirams.re.kr [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2014-07-25

    Highlights: • UPR activation precedes caspase activation in irradiated IEC-6 cells. • Chemical ER stress inducers radiosensitize IEC-6 cells. • siRNAs that targeted ER stress responses ameliorate IR-induced cell death. • Chemical chaperons prevent cell death in irradiated IEC-6 cells. - Abstract: Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.

  16. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

    Science.gov (United States)

    Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

    2012-01-01

    Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

  17. Preventive and ameliorating effects of citrus D-limonene on dyslipidemia and hyperglycemia in mice with high-fat diet-induced obesity.

    Science.gov (United States)

    Jing, Li; Zhang, Yu; Fan, Shengjie; Gu, Ming; Guan, Yu; Lu, Xiong; Huang, Cheng; Zhou, Zhiqin

    2013-09-05

    D-limonene is a major constituent in citrus essential oil, which is used in various foods as a flavoring agent. Recently, d-limonene has been reported to alleviate fatty liver induced by a high-fat diet. Here we determined the preventive and therapeutic effects of d-limonene on metabolic disorders in mice with high-fat diet-induced obesity. In the preventive treatment, d-limonene decreased the size of white and brown adipocytes, lowered serum triglyceride (TG) and fasting blood glucose levels, and prevented liver lipid accumulations in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, d-limonene reduced serum TG, low-density lipoprotein cholesterol (LDL-c) and fasting blood glucose levels and glucose tolerance, and increased serum high-density lipoprotein cholesterol (HDL-c) in obese mice. Using a reporter assay and gene expression analysis, we found that d-limonene activated peroxisome proliferator-activated receptor (PPAR)-α signaling, and inhibited liver X receptor (LXR)-β signaling. Our data suggest that the intake of d-limonene may benefit patients with dyslipidemia and hyperglycemia and is a potential dietary supplement for preventing and ameliorating metabolic disorders. © 2013 Elsevier B.V. All rights reserved.

  18. Evaluation of chronic stress indicators in geriatric and oncologic caregivers: a cross-sectional study.

    Science.gov (United States)

    Aguiló, Sira; García, Esther; Arza, Adriana; Garzón-Rey, Jorge M; Aguiló, Jordi

    2018-01-01

    Caregiving induces chronic stress with physical and psychological impact on informal caregivers health. Therefore, subjective and objective indicators are needed for the early diagnosis of pathologic stress to prevent the risk of developing stress-related diseases in caregivers. Our aim was to assess the self-perceived stress, that is, how and how much the stressor affects the individual, through endocrine, metabolic, and immunologic biomarkers levels in geriatric and oncologic informal caregivers. Informal caregivers and non-caregivers were invited to participate in a cross-sectional study at the Clinic Hospital of Barcelona. Demographic and lifestyle characteristics, self-perceived stress (Perceived Stress Scale, State-Trait Anxiety Inventory and Stress Visual Analogue Scale), and biomarkers (copeptin, glucose, glycated hemoglobin, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), cholesterol, triglycerides, α-amylase, cortisol, tumor necrosis factor (TNF-α), and Interleukins (IL-6 and IL-10)) were evaluated. Descriptive and non-parametric statistical data analysis were performed. Fifty-six subjects (19 non-caregivers, 17 geriatric caregivers, and 20 oncologic caregivers) participated. Median age (IQR) was 57 years (47-66) and 71.46% were women. Self-perceived stress was higher in oncologic caregivers than geriatric caregivers in all psychometric test analyzed (Wilcoxon Rank Sum test, p value  .05). These findings suggest that perceived stress is not homogeneous in the caregivers community and thus these two groups could be differentiated. These results provide the baseline information to initiate social actions addressed to each group of caregivers to increase their wellbeing.

  19. Radiation oxidative stress in cancer induction and prevention

    International Nuclear Information System (INIS)

    Meher, Prabodha Kumar; Mishra, Kaushala Prasad

    2017-01-01

    Exposure of cells to ionizing radiation causes generation of intracellular reactive oxygen species (ROS) which are implicated in the mechanism of carcinogenesis. Molecular steps involved in the transformation of normal cells to cancer cells have been enigmatic but generally believed to arise from aberration in cellular redox homeostasis. In normal cell function, a delicate balance is maintained between ROS generated in the metabolic process and level of endogenous antioxidant defense. ROS are known to regulate various cellular functions, such as cell division, signal transduction, and apoptosis. Cells experience oxidative stress when excess production of ROS occurs inside a cell upon exposure to external stress or agents. This redox imbalance affects the cellular functions due to DNA strand breaks, chromosomal aberrations, gene mutations, alteration in signal transduction, and inhibition of apoptosis leading to induction of cancer and other diseases. Radiation-induced ROS are involved in initiation and promotion of carcinogenesis. Therefore, detoxification of ROS by exogenous antioxidants including dietary polyphenols offers an important strategy for cancer prevention. Recent research results have shown that resistance of cancer stem cells to therapies is linked to low level of ROS. Interestingly, in vitro and in vivo experiments have reported that radiotherapy- and chemotherapy-induced ROS in cytosol sensitize the tumor cells to death, resulting in tumor growth retardation. This review is an attempt to delineate mechanisms of ROS in carcinogenesis and prevention by dietary compounds. Natural polyphenols and dietary antioxidants hold potential to prevent cancer. Interventions in ROS-mediated signal alteration, apoptosis activation, and modulation of epigenetic processes may offer effective cancer prevention strategy. (author)

  20. Work stress prevention needs of employees and supervisors.

    Science.gov (United States)

    Havermans, Bo M; Brouwers, Evelien P M; Hoek, Rianne J A; Anema, Johannes R; van der Beek, Allard J; Boot, Cécile R L

    2018-05-21

    Work stress prevention can reduce health risks for individuals, as well as organisational and societal costs. The success of work stress interventions depends on proper implementation. Failure to take into account the needs of employees and supervisors can hinder intervention implementation. This study aimed to explore employee and supervisor needs regarding organisational work stress prevention. Semi-structured telephone interviews were conducted with employees (n = 7) and supervisors (n = 8) from different sectors, such as the finance, health care, and services industry. The interviews focused on respondents' needs regarding the prevention of work stress within an organisational setting. Performing thematic analysis, topics and themes were extracted from the verbatim transcribed interviews using Atlas.ti. Both employees and supervisors reported a need for: 1) communication about work stress, 2) attention for determinants of work stress, 3) supportive circumstances (prerequisites) for work stress prevention, 4) involvement of various stakeholders in work stress prevention, and 5) availability of work stress prevention measures. Both employees and supervisors expressed the need for supervisors to communicate about work stress. Employees and supervisors reported similar psychosocial work factors that should be targeted for prevention (e.g., social support and autonomy). There was greater variety in the sub-themes within communication about work stress and supportive circumstances for work stress prevention in supervisor responses, and greater variety in the sub-themes within availability of work stress prevention measures in employee responses. Both employees and supervisors were explicit about who should take part in communication about work stress, what prerequisites for work stress prevention should exist, and which stakeholders should be involved. These results can inform work stress prevention practice, supporting selection and implementation of

  1. Stress Prevention@Work : A study protocol for the evaluation of a multifaceted integral stress prevention strategy to prevent employee stress in a healthcare organization: a cluster controlled trial

    NARCIS (Netherlands)

    Hoek, R.J.A.; Havermans, B.M.; Houtman, I.L.D.; Brouwers, E.P.M.; Heerkens, Y.F.; Zijlstra-vlasveld, M.C.; Anema, J.R.; van der Beek, A.J.; Boot, C.R.L.

    2018-01-01

    Adequate implementation of work-related stress management interventions can reduce or prevent work-related stress and sick leave in organizations. We developed a multifaceted integral stress-prevention strategy for organizations from several sectors that includes a digital platform and collaborative

  2. Stress Prevention@Work: a study protocol for the evaluation of a multifaceted integral stress prevention strategy to prevent employee stress in a healthcare organization: a cluster controlled trial

    NARCIS (Netherlands)

    Hoek, R.J.A.; Havermans, B.M.; Houtman, I.L.D.; Brouwers, E.P.M.; Heerkens, Y.F.; Zijlstra-Vlasveld, M.C.; Anema, J.R.; Beek, A.J. van der; Boot, C.R.L.

    2017-01-01

    Background. Adequate implementation of work-related stress management interventions can reduce or prevent work-related stress and sick leave in organizations. We developed a multifaceted integral stress-prevention strategy for organizations from several sectors that includes a digital platform and

  3. Salubrious effects of oxytocin on social stress-induced deficits

    Science.gov (United States)

    Smith, Adam S.; Wang, Zuoxin

    2012-01-01

    Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

  4. Effect of Short-Term High Fat Diet Inducing Obesity on Hematological, Some Biochemical Parameters and Testicular Oxidative Stress in Male Rats

    Directory of Open Access Journals (Sweden)

    Sherif M. Shawky

    2015-10-01

    Full Text Available Obesity constitutes a health problem due to its increasing worldwide prevalence. Among the health detriments caused by obesity, reproduction is disrupted. Some studies have shown a relationship between obesity and infertility, but until now it remains controversial. The objective of the current work was to examine the effect of diet-induced obesity on blood parameters, liver and kidney function tests, lipid profile and testicular oxidative stress. For that purpose, Male rats were fed ad libitum with a standard diet (control group; n.= 15 and high fat diet (HFD group; n.= 15 for 6 weeks. Hematological parameters, urea, creatinine, albumin were similar between the two groups. Intergroup testosterone levels were also comparable. The high fat diet induced significant increase in serum triglycerides, cholesterol, low density lipoprotein and very low density lipoprotein cholesterol concentrations. This diet also increases significantly alanine aminotransferase and aspartate aminotransferase activities and decreased total protein level and high-density lipoprotein cholesterol concentration. Furthermore, HFD showed a significant increasing in malondialdehyde contents in testes and decreasing in superoxide dismutase activity, the results of this study concluded that short-term high fat diet affect on liver enzymes and causing oxidative stress in testes.

  5. Effects of the antipsychotic paliperidone on stress-induced changes in the endocannabinoid system in rat prefrontal cortex.

    Science.gov (United States)

    MacDowell, Karina S; Sayd, Aline; García-Bueno, Borja; Caso, Javier R; Madrigal, José L M; Leza, Juan Carlos

    2017-09-01

    Objectives There is a need to explore novel mechanisms of action of existing/new antipsychotics. One potential candidate is the endocannabinoid system (ECS). The present study tried to elucidate the effects of the antipsychotic paliperidone on stress-induced ECS alterations. Methods Wister rats were submitted to acute/chronic restraint stress. Paliperidone (1 mg/kg) was given prior each stress session. Cannabinoid receptors and endocannabinoids (eCBs) synthesis and degradation enzymes were measured in prefrontal cortex (PFC) samples by RT-PCR and Western Blot. Results In the PFC of rats exposed to acute stress, paliperidone increased CB1 receptor (CB1R) expression. Furthermore, paliperidone increased the expression of the eCB synthesis enzymes N-acylphosphatidylethanolamine- hydrolysing phospholipase D and DAGLα, and blocked the stress-induced increased expression of the degrading enzyme fatty acid amide hydrolase. In chronic conditions, paliperidone prevented the chronic stress-induced down-regulation of CB1R, normalised DAGLα expression and reverted stress-induced down-regulation of the 2-AG degrading enzyme monoacylglycerol lipase. ECS was analysed also in periphery. Acute stress decreased DAGLα expression, an effect prevented by paliperidone. Contrarily, chronic stress increased DAGLα and this effect was potentiated by paliperidone. Conclusions The results obtained described a preventive effect of paliperidone on stress-induced alterations in ECS. Considering the diverse alterations on ECS described in psychotic disease, targeting ECS emerges as a new therapeutic possibility.

  6. Spirulina improves antioxidant status by reducing oxidative stress in rabbits fed a high-cholesterol diet.

    Science.gov (United States)

    Kim, Mi Yeon; Cheong, Sun Hee; Lee, Jeung Hee; Kim, Min Ji; Sok, Dai-Eun; Kim, Mee Ree

    2010-04-01

    The beneficial effect of Spirulina (Spirulina platensis) on tissue lipid peroxidation and oxidative DNA damage was tested in the hypercholesterolemic New Zealand White rabbit model. After hypercholesterolemia was induced by feeding a high cholesterol (0.5%) diet (HCD) for 4 weeks, then HCD supplemented with 1% or 5% Spirulina (SP1 or SP5, respectively) was provided for an additional 8 weeks. Spirulina supplementation significantly reduced the increased lipid peroxidation level in HCD-fed rabbits, and levels recovered to control values. Oxidative stress biomarkers such as glutathione, glutathione peroxidase, glutathione reductase, and glutathione S-transferase were significantly improved in the liver and red blood cells of rabbits fed SP1. Furthermore, SP5 induced antioxidant enzyme activity by 3.1-fold for glutathione, 2.5-fold for glutathione peroxidase, 2.7-fold for glutathione reductase, and 2.3-fold for glutathione S-transferase in liver, compared to the HCD group. DNA damage in lymphocytes was significantly reduced in both the SP1 and SP5 groups, based on the comet assay. Findings from the present study suggest that dietary supplementation with Spirulina may be useful to protect the cells from lipid peroxidation and oxidative DNA damage.

  7. Early Psychological Counseling for the Prevention of Posttraumatic Stress Induced by Acute Coronary Syndrome: The MI-SPRINT Randomized Controlled Trial.

    Science.gov (United States)

    von Känel, Roland; Barth, Jürgen; Princip, Mary; Meister-Langraf, Rebecca E; Schmid, Jean-Paul; Znoj, Hansjörg; Herbert, Claudia; Schnyder, Ulrich

    2018-01-01

    Acute coronary syndrome (ACS)-induced posttraumatic stress disorder (PTSD) and clinically significant PTSD symptoms (PTSS) are found in 4 and 12% of patients, respectively. We hypothesized that trauma-focused counseling prevents the incidence of ACS-induced PTSS. Within 48 h of hospital admission, 190 patients with high distress during ACS were randomized to a single-session intervention of either trauma-focused counseling or an active control intervention targeting the general role of stress in patients with heart disease. Blind interviewer-rated PTSS (primary outcome) and additional health outcomes were assessed at 3 months of follow-up. Trial results about prevalence were compared with data from previous studies on the natural incidence of ACS-induced PTSS/PTSD. Intention-to-treat analyses revealed no difference in interviewer-rated PTSS between trauma-focused counseling (mean, 11.33; 95% Cl, 9.23-13.43) and stress counseling (9.88; 7.36-12.40; p = 0.40), depressive symptoms (6.01, 4.98-7.03, vs. 4.71, 3.65-5.77; p = 0.08), global psychological distress (5.15, 4.07-6.23, vs. 3.80, 2.60-5.00; p = 0.11), and the risk for cardiovascular-related hospitalization/all-cause mortality (OR, 0.67; 95% CI, 0.37-1.23). Self-rated PTSS indicated less beneficial effects with trauma-focused (6.54; 4.95-8.14) versus stress counseling (3.74; 2.39-5.08; p = 0.017). The completer analysis (154 cases) confirmed these findings. The prevalence rates of interviewer-rated PTSD (0.5%, 1/190) and self-rated PTSS were in this trial much lower than in meta-analyses and observation studies from the same cardiology department. Benefits were not seen for trauma-focused counseling when compared with an active control intervention. Nonetheless, in distressed ACS patients, individual, single-session, early psychological counseling shows potential as a means to prevent posttraumatic responses, but trauma-focused early treatments should probably be avoided. © 2018 S. Karger AG, Basel.

  8. Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet.

    Science.gov (United States)

    Ma, Xiaoqing; Du, Wenhua; Shao, Shanshan; Yu, Chunxiao; Zhou, Lingyan; Jing, Fei

    2018-01-01

    Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission electron microscopy, real-time PCR for gene expression levels, and western blots for protein expression levels. ER stress was induced in HepG2 cells with palmitic acid and the effects of vildagliptin were investigated. Results. HFD mice showed increased liver weight/body weight (20.27%) and liver triglycerides (314.75%) compared to CD mice, but these decreased by 9.27% and 21.83%, respectively, in V-HFD mice. In the liver, HFD induced the expression of ER stress indicators significantly, which were obviously decreased by vildagliptin. In vitro, the expressions of molecular indicators of ER stress were reduced in HepG2 when vildagliptin was administered. Conclusions. Vildagliptin alleviates hepatic ER stress in a mouse high fat diet model. In HepG2 cells, vildagliptin directly reduced ER stress. Therefore, vildagliptin may be a potential agent for nonalcoholic fatty liver disease.

  9. Guanosine prevents behavioral alterations in the forced swimming test and hippocampal oxidative damage induced by acute restraint stress.

    Science.gov (United States)

    Bettio, Luis E B; Freitas, Andiara E; Neis, Vivian B; Santos, Danúbia B; Ribeiro, Camille M; Rosa, Priscila B; Farina, Marcelo; Rodrigues, Ana Lúcia S

    2014-12-01

    Guanosine is a guanine-based purine that modulates glutamate uptake and exerts neurotrophic and neuroprotective effects. In a previous study, our group demonstrated that this endogenous nucleoside displays antidepressant-like properties in a predictive animal model. Based on the role of oxidative stress in modulating depressive disorders as well as on the association between the neuroprotective and antioxidant properties of guanosine, here we investigated if its antidepressant-like effect is accompanied by a modulation of hippocampal oxidant/antioxidant parameters. Adult Swiss mice were submitted to an acute restraint stress protocol, which is known to cause behavioral changes that are associated with neuronal oxidative damage. Animals submitted to ARS exhibited an increased immobility time in the forced swimming test (FST) and the administration of guanosine (5mg/kg, p.o.) or fluoxetine (10mg/kg, p.o., positive control) before the exposure to stressor prevented this alteration. Moreover, the significantly increased levels of hippocampal malondialdehyde (MDA; an indicator of lipid peroxidation), induced by ARS were not observed in stressed mice treated with guanosine. Although no changes were found in the hippocampal levels of reduced glutathione (GSH), the group submitted to ARS procedure presented enhanced glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) activities and reduced catalase (CAT) activity in the hippocampus. Guanosine was able to prevent the alterations in GPx, GR, CAT activities, and in SOD/CAT activity ratio, but potentiated the increase in SOD activity elicited by ARS. Altogether, the present findings indicate that the observed antidepressant-like effects of guanosine might be related, at least in part, to its capability of modulating antioxidant defenses and mitigating hippocampal oxidative damage induced by ARS. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Neuroprotective effects of phytosterol esters against high cholesterol-induced cognitive deficits in aged rat.

    Science.gov (United States)

    Rui, Xu; Wenfang, Li; Jing, Cheng; Meng, Chen; Chengcheng, Ding; Jiqu, Xu; Shuang, Rong

    2017-03-22

    Accumulating epidemiological and experimental studies have confirmed that a high-cholesterol diet is detrimental to cognitive performance in animal models. Phytosterols, a class of naturally occurring structural components in plant foods, have been demonstrated to possess cholesterol-lowering and antioxidant effects. Phytosterol esters (PSE) are esters of phytosterol. The aim of this study was to evaluate the neuroprotective effects of PSE on cognitive deficit induced by a cholesterol-enriched diet in aged rats, and to explore their underlying mechanisms for these effects. Based on their Morris water maze performance, the latencies differed by <1.5 standard deviations (SDs) on days 3-5 of testing, 60 rats were chosen from 12-month-old female Sprague Dawley aged rats and were randomized into three groups, which were fed either a control diet, a high cholesterol diet (HCD) or a high-cholesterol diet supplemented with 2% PSE (HCD + PSE) for 6 months. In our study, we found that PSE treatment maintained the body weight balance, reduced the serum lipid levels, and improved the cognitive performance of aged rats in the Morris water maze test, as evaluated by shortened escape latencies. Importantly, histological and immunohistochemical results in the brain showed that PSE supplementation may have a neuroprotective effect that alleviates neuroinflammation in aged rats. This neuroprotective effect significantly inhibited degeneration, resulting in a significant increase in the number of pyramidal cells and an apparent decrease in the number of astrocytes compared to rats that were fed only a HCD. Furthermore, PSE improved cholinergic activities by restoring the acetylcholine (ACh) content and decreasing acetylcholinesterase (AChE) activity in the cerebral cortex, as well as by elevating choline acetyl transferase (ChAT) activity in the hippocampus and the cerebral cortex. These results suggest that PSE can play a useful role in alleviating cognitive deficit induced by a

  11. Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease

    Directory of Open Access Journals (Sweden)

    Agostino Di Ciaula

    2013-01-01

    Full Text Available Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk.

  12. Laforin prevents stress-induced polyglucosan body formation and Lafora disease progression in neurons.

    Science.gov (United States)

    Wang, Yin; Ma, Keli; Wang, Peixiang; Baba, Otto; Zhang, Helen; Parent, Jack M; Zheng, Pan; Liu, Yang; Minassian, Berge A; Liu, Yan

    2013-08-01

    Glycogen, the largest cytosolic macromolecule, is soluble because of intricate construction generating perfect hydrophilic-surfaced spheres. Little is known about neuronal glycogen function and metabolism, though progress is accruing through the neurodegenerative epilepsy Lafora disease (LD) proteins laforin and malin. Neurons in LD exhibit Lafora bodies (LBs), large accumulations of malconstructed insoluble glycogen (polyglucosans). We demonstrated that the laforin-malin complex reduces LBs and protects neuronal cells against endoplasmic reticulum stress-induced apoptosis. We now show that stress induces polyglucosan formation in normal neurons in culture and in the brain. This is mediated by increased glucose-6-phosphate allosterically hyperactivating muscle glycogen synthase (GS1) and is followed by activation of the glycogen digesting enzyme glycogen phosphorylase. In the absence of laforin, stress-induced polyglucosans are undigested and accumulate into massive LBs, and in laforin-deficient mice, stress drastically accelerates LB accumulation and LD. The mechanism through which laforin-malin mediates polyglucosan degradation remains unclear but involves GS1 dephosphorylation by laforin. Our work uncovers the presence of rapid polyglucosan metabolism as part of the normal physiology of neuroprotection. We propose that deficiency in the degradative phase of this metabolism, leading to LB accumulation and resultant seizure predisposition and neurodegeneration, underlies LD.

  13. Institutional Preventive Stress Management.

    Science.gov (United States)

    Quick, James C.

    1987-01-01

    Stress is an inevitable characteristic of academic life, but colleges and universities can introduce stress management activities at the organizational level to avert excessive tension. Preventive actions are described, including flexible work schedules and social supports. (Author/MSE)

  14. Stress-induced endocrine response and anxiety: the effects of comfort food in rats.

    Science.gov (United States)

    Ortolani, Daniela; Garcia, Márcia Carvalho; Melo-Thomas, Liana; Spadari-Bratfisch, Regina Celia

    2014-05-01

    The long-term effects of comfort food in an anxiogenic model of stress have yet to be analyzed. Here, we evaluated behavioral, endocrine and metabolic parameters in rats submitted or not to chronic unpredictable mild stress (CUMS), with access to commercial chow alone or to commercial chow and comfort food. Stress did not alter the preference for comfort food but decreased food intake. In the elevated plus-maze (EPM) test, stressed rats were less likely to enter/remain in the open arms, as well as being more likely to enter/remain in the closed arms, than were control rats, both conditions being more pronounced in the rats given access to comfort food. In the open field test, stress decreased the time spent in the centre, independent of diet; neither stress nor diet affected the number of crossing, rearing or grooming episodes. The stress-induced increase in serum corticosterone was attenuated in rats given access to comfort food. Serum concentration of triglycerides were unaffected by stress or diet, although access to comfort food increased total cholesterol and glucose. It is concluded that CUMS has an anorexigenic effect. Chronic stress and comfort food ingestion induced an anxiogenic profile although comfort food attenuated the endocrine stress response. The present data indicate that the combination of stress and access to comfort food, common aspects of modern life, may constitute a link among stress, feeding behavior and anxiety.

  15. Supplementation of Syzygium cumini seed powder prevented obesity, glucose intolerance, hyperlipidemia and oxidative stress in high carbohydrate high fat diet induced obese rats.

    Science.gov (United States)

    Ulla, Anayt; Alam, Md Ashraful; Sikder, Biswajit; Sumi, Farzana Akter; Rahman, Md Mizanur; Habib, Zaki Farhad; Mohammed, Mostafe Khalid; Subhan, Nusrat; Hossain, Hemayet; Reza, Hasan Mahmud

    2017-06-02

    Obesity and related complications have now became epidemic both in developed and developing countries. Cafeteria type diet mainly composed of high fat high carbohydrate components which plays a significant role in the development of obesity and metabolic syndrome. This study investigated the effect of Syzygium cumini seed powder on fat accumulation and dyslipidemia in high carbohydrate high fat diet (HCHF) induced obese rats. Male Wistar rats were fed with HCHF diet ad libitum, and the rats on HCHF diet were supplemented with Syzygium cumini seed powder for 56 days (2.5% w/w of diet). Oral glucose tolerance test, lipid parameters, liver marker enzymes (AST, ALT and ALP) and lipid peroxidation products were analyzed at the end of 56 days. Moreover, antioxidant enzyme activities were also measured in all groups of rats. Supplementation with Syzygium cumini seed powder significantly reduced body weight gain, white adipose tissue (WAT) weights, blood glucose, serum insulin, and plasma lipids such as total cholesterol, triglyceride, LDL and HDL concentration. Syzygium cumini seed powder supplementation in HCHF rats improved serum aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (ALP) activities. Syzygium cumini seed powder supplementation also reduced the hepatic thiobarbituric acid reactive substances (TBARS) and elevated the antioxidant enzyme superoxide dismutase (SOD) and catalase (CAT) activities as well as increased glutathione (GSH) concentration. In addition, histological assessment showed that Syzygium cumini seed powder supplementation prevented inflammatory cell infiltration; fatty droplet deposition and fibrosis in liver of HCHFD fed rats. Our investigation suggests that Syzygium cumini seed powder supplementation prevents oxidative stress and showed anti-inflammatory and antifibrotic activity in liver of HCHF diet fed rats. In addition, Syzygium cumini seed powder may be beneficial in ameliorating insulin

  16. Plasticity in the olfactory bulb of the maternal mouse is prevented by gestational stress

    Science.gov (United States)

    Belnoue, Laure; Malvaut, Sarah; Ladevèze, Elodie; Abrous, Djoher Nora; Koehl, Muriel

    2016-01-01

    Maternal stress is associated with an altered mother-infant relationship that endangers offspring development, leading to emotional/behavioral problems. However, little research has investigated the stress-induced alterations of the maternal brain that could underlie such a disruption of mother-infant bonding. Olfactory cues play an extensive role in the coordination of mother-infant interactions, suggesting that motherhood may be associated to enhanced olfactory performances, and that this effect may be abolished by maternal stress. To test this hypothesis, we analyzed the impact of motherhood under normal conditions or after gestational stress on olfactory functions in C57BL/6 J mice. We report that gestational stress alters maternal behavior and prevents both mothers’ ability to discriminate pup odors and motherhood-induced enhancement in odor memory. We investigated adult bulbar neurogenesis as a potential mechanism of the enhanced olfactory function in mothers and found that motherhood was associated with an increased complexity of the dendritic tree of newborn neurons. This motherhood-evoked remodeling was totally prevented by gestational stress. Altogether, our results may thus provide insight into the neural changes that could contribute to altered maternal behavior in stressed mothers. PMID:27886228

  17. Metformin prevents endoplasmic reticulum stress-induced apoptosis through AMPK-PI3K-c-Jun NH2 pathway

    Science.gov (United States)

    Jung, T.W.; Lee, M.W.; Lee, Y.-J.; Kim, S.M.

    2012-01-01

    Type 2 diabetes mellitus is thought to be partially associated with endoplasmic reticulum (ER) stress toxicity on pancreatic beta cells and the result of decreased insulin synthesis and secretion. In this study, we showed that a well-known insulin sensitizer, metformin, directly protects against dysfunction and death of ER stress-induced NIT-1 cells (a mouse pancreatic beta cell line) via AMP-activated protein kinase (AMPK) and phosphatidylinositol-3 (PI3) kinase activation. We also showed that exposure of NIT-1 cells to metformin (5mM) increases cellular resistance against ER stress-induced NIT-1 cell dysfunction and death. AMPK and PI3 kinase inhibitors abolished the effect of metformin on cell function and death. Metformin-mediated protective effects on ER stress-induced apoptosis were not a result of an unfolded protein response or the induced inhibitors of apoptotic proteins. In addition, we showed that exposure of ER stressed-induced NIT-1 cells to metformin decreases the phosphorylation of c-Jun NH(2) terminal kinase (JNK). These data suggest that metformin is an important determinant of ER stress-induced apoptosis in NIT-1 cells and may have implications for ER stress-mediated pancreatic beta cell destruction via regulation of the AMPK-PI3 kinase-JNK pathway.

  18. LR-90 prevents methylglyoxal-induced oxidative stress and apoptosis in human endothelial cells

    Science.gov (United States)

    Figarola, James L.; Singhal, Jyotsana; Rahbar, Samuel; Awasthi, Sanjay

    2014-01-01

    Methylglyoxal (MGO) is a highly reactive dicarbonyl compound known to induce cellular injury and cytoxicity, including apoptosis in vascular cells. Vascular endothelial cell apoptosis has been implicated in the pathophysiology and progression of atherosclerosis. We investigated whether the advanced glycation end-product inhibitor LR-90 could prevent MGO-induced apoptosis in human umbilical vascular endothelial cells (HUVECs). HUVECs were pre-treated with LR-90 and then stimulated with MGO. Cell morphology, cytotoxicity and apoptosis were evaluated by light microscopy, MTT assay, and Annexin V-FITC and propidium iodide double staining, respectively. Levels of Bax, Bcl-2, cytochrome c, mitogen-activated protein kinases (MAPKs) and caspase activities were assessed by Western blotting. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. LR-90 dose-dependently prevented MGO-associated HUVEC cytotoxicity and apoptotic biochemical changes such as loss of MMP, increased Bax/Bcl-2 protein ratio, mitochondrial cytochrome c release and activation of caspase-3 and 9. Additionally, LR-90 blocked intracellular ROS formation and MAPK (p44/p42, p38, JNK) activation, though the latter seem to be not directly involved in MGO-induced HUVEC apoptosis. LR-90 prevents MGO-induced HUVEC apoptosis by inhibiting ROS and associated mitochondrial-dependent apoptotic signaling cascades, suggesting that LR-90 possess cytoprotective ability which could be beneficial in prevention of diabetic related-atherosclerosis. PMID:24615331

  19. Antihyperglycemic and Antihyperlipidemic Activity of Hydroponic Stevia rebaudiana Aqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits

    Directory of Open Access Journals (Sweden)

    Anush Aghajanyan

    2017-01-01

    Full Text Available Diabetes mellitus (DM is a serious worldwide problem related to human hyperglycemia. Thus, herbal preparations with antihyperglycemic properties especially leaf extracts of hydroponic Stevia rebaudiana (SR would be useful in hyperglycemia treatment. The antihyperglycemic potential of this medicinal plant grown using hydroponics methods has been evaluated. Significant reduction of some biochemical characteristics for sugars and fatty acids in blood, liver, and muscle especially fasting glucose levels, serum triglycerides, LDL-cholesterol, total cholesterol levels, and increased HDL-cholesterol ones was shown with SR aqueous extract treatment. Therefore, the aqueous extract of SR is suggested to have antihyperglycemic and antihyperlipidemic activity and to restore liver and muscle glycogen levels (hepatoprotective effects in hyperglycemia induced by immobilization stress in rabbits and might be recommended for treatment of DM (hyperglycemia.

  20. Antihyperglycemic and Antihyperlipidemic Activity of Hydroponic Stevia rebaudiana Aqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits

    Science.gov (United States)

    Aghajanyan, Anush; Movsisyan, Zaruhi

    2017-01-01

    Diabetes mellitus (DM) is a serious worldwide problem related to human hyperglycemia. Thus, herbal preparations with antihyperglycemic properties especially leaf extracts of hydroponic Stevia rebaudiana (SR) would be useful in hyperglycemia treatment. The antihyperglycemic potential of this medicinal plant grown using hydroponics methods has been evaluated. Significant reduction of some biochemical characteristics for sugars and fatty acids in blood, liver, and muscle especially fasting glucose levels, serum triglycerides, LDL-cholesterol, total cholesterol levels, and increased HDL-cholesterol ones was shown with SR aqueous extract treatment. Therefore, the aqueous extract of SR is suggested to have antihyperglycemic and antihyperlipidemic activity and to restore liver and muscle glycogen levels (hepatoprotective effects) in hyperglycemia induced by immobilization stress in rabbits and might be recommended for treatment of DM (hyperglycemia). PMID:28758125

  1. Occupational Stress: Preventing Suffering, Enhancing Wellbeing.

    Science.gov (United States)

    Quick, James Campbell; Henderson, Demetria F

    2016-04-29

    Occupational stress is a known health risk for a range of psychological, behavioral, and medical disorders and diseases. Organizations and individuals can mitigate these disorders through preventive stress management and enhanced wellbeing. This article addresses, first, the known health risk evidence related to occupational stress; second, the use of preventive stress management in organizations as the framework for intervention; and third, the emerging domain of enhancing wellbeing, which strengthens the individual. Premature death and disability along with chronic suffering from occupational stress are not inevitable, despite being known outcome risks.

  2. Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet

    OpenAIRE

    Ma, Xiaoqing; Du, Wenhua; Shao, Shanshan; Yu, Chunxiao; Zhou, Lingyan; Jing, Fei

    2018-01-01

    Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission el...

  3. [Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion].

    Science.gov (United States)

    Blanchard, Claire; Moreau, François; Cariou, Bertrand; Le May, Cédric

    2014-10-01

    The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases. © 2014 médecine/sciences – Inserm.

  4. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study

    DEFF Research Database (Denmark)

    Goldstein, L.B.; Amarenco, P.; Szarek, M.

    2008-01-01

    BACKGROUND: In the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study, atorvastatin 80 mg/day reduced the risk of stroke in patients with recent stroke or TIA. Post hoc analysis found this overall benefit included an increase in the numbers of treated patients having......: Of 4,731 patients, 67% had ischemic strokes, 31% TIAs, and 2% hemorrhagic strokes as entry events. In addition to atorvastatin treatment (HR 1.68, 95% CI 1.09 to 2.59, p = 0.02), Cox multivariable regression including baseline variables significant in univariable analyses showed that hemorrhagic stroke...... and treatment. Multivariable analyses also found that having Stage 2 (JNC-7) hypertension at the last study visit before a hemorrhagic stroke increased risk (HR 6.19, 95% CI 1.47 to 26.11, p = 0.01), but there was no effect of most recent LDL-cholesterol level in those treated with atorvastatin. CONCLUSIONS...

  5. National Cholesterol Education Month

    Centers for Disease Control (CDC) Podcasts

    2009-09-01

    Do you know your cholesterol numbers? Your doctor can do a simple test to check your cholesterol levels and help you make choices that lower your risk for heart disease and stroke.  Created: 9/1/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/9/2009.

  6. Preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed obese rats.

    Science.gov (United States)

    Maithilikarpagaselvi, Nachimuthu; Sridhar, Magadi Gopalakrishna; Swaminathan, Rathinam Palamalai; Sripradha, Ramalingam

    2016-06-01

    The present study investigated the beneficial effects of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed male Wistar rats. Five-month-old male Wistar rats (n=20) were divided into two groups (10 rats in each group). Among the two groups, one group received 30 % high-fat diet (HFD) and another group received 30 % HFD with curcumin (200 mg/kg body weight). Food intake, body weight and biochemical parameters were measured at the beginning and at the end of the study. After 10 weeks, oxidative stress parameters in skeletal muscle and hepatic triacylglycerol (TAG) content were estimated. Histological examinations of the liver samples were performed at the end of the experiment. High-fat feeding caused increase in body weight, liver and adipose tissue mass. Rats fed with HFD showed increased levels of fasting plasma glucose, insulin, Homeostasis Model Assessment for Insulin resistance (HOMA-IR), total cholesterol (TC), TAG, very low density lipoprotein cholesterol (VLDL-c) and decreased high-density lipoprotein cholesterol (HDL-c). There was also increase in the plasma inflammatory markers [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP)] and skeletal muscle oxidative stress parameters [malondialdehyde (MDA), total oxidant status (TOS)] in these rats. In addition, high-fat feeding increased liver TAG content and caused fat accumulation in the liver. Treatment with curcumin significantly reduced body weight, relative organ weights (liver, adipose tissue), glucose, insulin and HOMA-IR. Curcumin supplementation decreased plasma levels of TC, TAG, VLDL-c, TNF-α and increased HDL-c. Administration of curcumin also reduced MDA, TOS in skeletal muscle, hepatic TAG content and liver fat deposition. Curcumin supplementation improved HFD-induced dyslipidemia, oxidative stress, inflammation and insulin resistance.

  7. Mitotic spindle defects and chromosome mis-segregation induced by LDL/cholesterol-implications for Niemann-Pick C1, Alzheimer's disease, and atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Antoneta Granic

    Full Text Available Elevated low-density lipoprotein (LDL-cholesterol is a risk factor for both Alzheimer's disease (AD and Atherosclerosis (CVD, suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy-in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1 high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis' first prediction, 2 Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3 oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL, induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4 LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5 cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6 ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol's aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol

  8. The influence of saponins on cell membrane cholesterol.

    Science.gov (United States)

    Böttger, Stefan; Melzig, Matthias F

    2013-11-15

    We studied the influence of structurally different saponins on the cholesterol content of cellular membranes. Therefore a cell culture model using ECV-304 urinary bladder carcinoma cells was developed. To measure the cholesterol content we used radiolabeled (3)H-cholesterol which is chemically and physiologically identical to natural cholesterol. The cells were pre-incubated with (3)H-cholesterol and after a medium change, they were treated with saponins to assess a saponin-induced cholesterol liberation from the cell membrane. In another experiment the cells were pre-incubated with saponins and after a medium change, they were treated with (3)H-cholesterol to assess a saponin-induced inhibition of cholesterol uptake into the cell membrane. Furthermore, the membrane toxicity of all applied saponins was analyzed using extracellular LDH quantification and the general cytotoxicity was analyzed using a colorimetric MTT-assay and DNA quantification. Our results revealed a correlation between membrane toxicity and general cytotoxicity. We also compared the results from the experiments on the saponin-induced cholesterol liberation as well as the saponin-induced inhibition of cholesterol uptake with the membrane toxicity. A significant reduction in the cell membrane cholesterol content was noted for those saponins who showed membrane toxicity (IC50 saponins either liberated (3)H-cholesterol from intact cell membranes or blocked the integration of supplemented (3)H-cholesterol into the cell membrane. Saponins with little influence on the cell membrane (IC50 >100 μM) insignificantly altered the cell membrane cholesterol content. The results suggested that the general cytotoxicity of saponins is mainly dependent on their membrane toxicity and that the membrane toxicity might be caused by the loss of cholesterol from the cell membrane. We also analyzed the influence of a significantly membrane toxic saponin on the cholesterol content of intracellular membranes such as those

  9. Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet

    Directory of Open Access Journals (Sweden)

    Xiaoqing Ma

    2018-01-01

    Full Text Available Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD, high fat diet (HFD, and HFD administered with vildagliptin (50 mg/Kg (V-HFD. After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission electron microscopy, real-time PCR for gene expression levels, and western blots for protein expression levels. ER stress was induced in HepG2 cells with palmitic acid and the effects of vildagliptin were investigated. Results. HFD mice showed increased liver weight/body weight (20.27% and liver triglycerides (314.75% compared to CD mice, but these decreased by 9.27% and 21.83%, respectively, in V-HFD mice. In the liver, HFD induced the expression of ER stress indicators significantly, which were obviously decreased by vildagliptin. In vitro, the expressions of molecular indicators of ER stress were reduced in HepG2 when vildagliptin was administered. Conclusions. Vildagliptin alleviates hepatic ER stress in a mouse high fat diet model. In HepG2 cells, vildagliptin directly reduced ER stress. Therefore, vildagliptin may be a potential agent for nonalcoholic fatty liver disease.

  10. C3 deposition in cholesterol-induced atherosclerosis in rabbits: a possible etiologic role for complement in atherogenesis.

    Science.gov (United States)

    Pang, A S; Katz, A; Minta, J O

    1979-09-01

    Hypercholesterolemia was induced in rabbits by feeding Purina Chow supplemented with cholesterol (5 g/kg body weight/day). The serum cholesterol levels of these rabbits increased progressively and after 3 to 5 months were 4 to 9-fold greater than those of the control animals. Decrease in total hemolytic complement was not apparent during the feeding regimen. Morphologic examination of aortae of these hypercholesterolemic rabbits showed typical atherosclerotic intimal plaques. Immunofluorescent microscopy with fluorescein (F)-labeled anti-rabbit C3 showed deposition of C3 in the intimal and inner medial layers as early as 3 months on high cholesterol diet. C3 deposits were also observed in the renal glomeruli and in the walls of coronary arteries. However, fluorescent studies failed to demonstrate the presence of IgG, IgM, and C4 at these sites. Tissues from control animals fed normal diets were negative for immunoglobulins, C3, and C4. These results suggest that the complement system may be implicated in the pathogenesis of cholesterol-induced atherosclerosis in rabbits.

  11. Endoplasmic reticulum stress as a novel mechanism in amiodarone-induced destructive thyroiditis.

    Science.gov (United States)

    Lombardi, Angela; Inabnet, William Barlow; Owen, Randall; Farenholtz, Kaitlyn Ellen; Tomer, Yaron

    2015-01-01

    Amiodarone (AMIO) is one of the most effective antiarrhythmic drugs available; however, its use is limited by a serious side effect profile, including thyroiditis. The mechanisms underlying AMIO thyroid toxicity have been elusive; thus, identification of novel approaches in order to prevent thyroiditis is essential in patients treated with AMIO. Our aim was to evaluate whether AMIO treatment could induce endoplasmic reticulum (ER) stress in human thyroid cells and the possible implications of this effect in AMIO-induced destructive thyroiditis. Here we report that AMIO, but not iodine, significantly induced the expression of ER stress markers including Ig heavy chain-binding protein (BiP), phosphoeukaryotic translation initiation factor 2α (eIF2α), CCAAT/enhancer-binding protein homologous protein (CHOP) and spliced X-box binding protein-1 (XBP-1) in human thyroid ML-1 cells and human primary thyrocytes. In both experimental systems AMIO down-regulated thyroglobulin (Tg) protein but had little effect on Tg mRNA levels, suggesting a mechanism involving Tg protein degradation. Indeed, pretreatment with the specific proteasome inhibitor MG132 reversed AMIO-induced down-regulation of Tg protein levels, confirming a proteasome-dependent degradation of Tg protein. Corroborating our findings, pretreatment of ML-1 cells and human primary thyrocytes with the chemical chaperone 4-phenylbutyric acid completely prevented the effect of AMIO on both ER stress induction and Tg down-regulation. We identified ER stress as a novel mechanism contributing to AMIO-induced destructive thyroiditis. Our data establish that AMIO-induced ER stress impairs Tg expression via proteasome activation, providing a valuable therapeutic avenue for the treatment of AMIO-induced destructive thyroiditis.

  12. Cholesterol-Induced Buckling in Physisorbed Polymer-Tethered Lipid Monolayers

    Directory of Open Access Journals (Sweden)

    Christoph A. Naumann

    2013-04-01

    Full Text Available The influence of cholesterol concentration on the formation of buckling structures is studied in a physisorbed polymer-tethered lipid monolayer system using epifluorescence microscopy (EPI and atomic force microscopy (AFM. The monolayer system, built using the Langmuir-Blodgett (LB technique, consists of 3 mol % poly(ethylene glycol (PEG lipopolymers and various concentrations of the phospholipid, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC, and cholesterol (CHOL. In the absence of CHOL, AFM micrographs show only occasional buckling structures, which is caused by the presence of the lipopolymers in the monolayer. In contrast, a gradual increase of CHOL concentration in the range of 0–40 mol % leads to fascinating film stress relaxation phenomena in the form of enhanced membrane buckling. Buckling structures are moderately deficient in CHOL, but do not cause any notable phospholipid-lipopolymer phase separation. Our experiments demonstrate that membrane buckling in physisorbed polymer-tethered membranes can be controlled through CHOL-mediated adjustment of membrane elastic properties. They further show that CHOL may have a notable impact on molecular confinement in the presence of crowding agents, such as lipopolymers. Our results are significant, because they offer an intriguing prospective on the role of CHOL on the material properties in complex membrane architecture.

  13. Protective Effect of γ-Irradiated Dried Powder of Artichoke Leaves against CCl4 Oxidative Stress Induced in Rat Liver

    International Nuclear Information System (INIS)

    Hamza, R.G.; El shahat, A.N.; Mekawey, H.M.S.

    2012-01-01

    Liver injuries are one of the most degenerative worldwide diseases and can lead to different complications. Artichoke (Cynara scolymus L.) is full of natural antioxidants and has hepato protective effect against liver toxicity. Gamma irradiation has been widely used as a first choice sterilization method of raw medicinal plants to be used in the phytotherapic industry worldwide .This study was designed to investigate the effect of dietary supplementation with γ- irradiated artichoke against carbon tetrachloride (CCl 4 )-induced oxidative stress and hepatotoxicity. The results of high performance liquid chromatography (HPLC) analysis of artichoke leaves indicated that the value of some of the main phenolic constituents was elevated under the effect of γ-irradiation (10 KGy). CCl 4 administration resulted in significant increase in the activity of serum alkaline phosphatase, gamma glutamyl transferase and transaminase in addition to an increase in the level of total bilirubine, malondialdehyde (MDA), glucose and the concentration of some lipid contents. Furthermore, CCl 4 administration reduced glutathione content, superoxides dismutase (SOD) and catalase (CAT) activity as well as a remarkable decrease in the level of insulin and high density lipoprotein-cholesterol was observed. In CCl 4 -treated rats dietary supplemented with either raw or γ-irradiated artichoke, a significant amelioration was observed on the adverse effects of the above mentioned parameters induced by CCl 4 administration. The present findings concluded that artichoke may be useful, as dietary supplement and possess phenolic compounds, for the prevention of oxidative stress-induced hepatotoxicity

  14. A Methyl-Balanced Diet Prevents CRF-Induced Prenatal Stress-Triggered Predisposition to Binge Eating-like Phenotype.

    Science.gov (United States)

    Schroeder, Mariana; Jakovcevski, Mira; Polacheck, Tamar; Lebow, Maya; Drori, Yonat; Engel, Mareen; Ben-Dor, Shifra; Chen, Alon

    2017-06-06

    Binge eating (BE) is a common aberrant form of eating behavior, characterized by overconsumption of food in a brief period of time. Recurrent episodes of BE constitute the BE disorder, which mostly affects females and is associated with early-life adversities. Here, we show that corticotropin releasing factor (CRF)-induced prenatal stress (PNS) in late gestation predisposes female offspring to BE-like behavior that coincides with hypomethylation of hypothalamic miR-1a and downstream dysregulation of the melanocortin system through Pax7/Pax3. Moreover, exposing the offspring to a methyl-balanced diet during adolescence prevents the dysregulation and predisposition from being triggered. We demonstrate that gestational programming, per se, will not lead to BE-like behavior, but pre-existing alterations due to prenatal programming are revealed only when challenged during adolescence. We provide experimental evidence for long-term epigenetic abnormalities stemming from PNS in predisposing female offspring to BE disorder as well as a potential non-invasive prevention strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Prazosin Prevents Increased Anxiety Behavior That Occurs in Response to Stress During Alcohol Deprivations.

    Science.gov (United States)

    Rasmussen, Dennis D; Kincaid, Carrie L; Froehlich, Janice C

    2017-01-01

    Stress-induced anxiety is a risk factor for relapse to alcohol drinking. The aim of this study was to test the hypothesis that the central nervous system (CNS)-active α 1 -adrenergic receptor antagonist, prazosin, would block the stress-induced increase in anxiety that occurs during alcohol deprivations. Selectively bred male alcohol-preferring (P) rats were given three cycles of 5 days of ad libitum voluntary alcohol drinking interrupted by 2 days of alcohol deprivation, with or without 1 h of restraint stress 4 h after the start of each of the first two alcohol deprivation cycles. Prazosin (1.0 or 1.5 mg/kg, IP) or vehicle was administered before each restraint stress. Anxiety-like behavior during alcohol deprivation following the third 5-day cycle of alcohol drinking (7 days after the most recent restraint stress ± prazosin treatment) was measured by performance in an elevated plus-maze and in social approach/avoidance testing. Rats that received constant alcohol access, or alcohol access and deprivations without stress or prazosin treatments in the first two alcohol deprivations did not exhibit augmented anxiety-like behavior during the third deprivation. In contrast, rats that had been stressed during the first two alcohol deprivations exhibited increased anxiety-like behavior (compared with control rats) in both anxiety tests during the third deprivation. Prazosin given before stresses in the first two cycles of alcohol withdrawal prevented increased anxiety-like behavior during the third alcohol deprivation. Prazosin treatment before stresses experienced during alcohol deprivations may prevent the increased anxiety during subsequent deprivation/abstinence that is a risk factor for relapse to alcohol drinking. Administration of prazosin before stresses during repetitive alcohol deprivations in male alcohol-preferring (P) rats prevents increased anxiety during a subsequent deprivation without further prazosin treatment. Prazosin treatment during repeated

  16. Scallop protein with endogenous high taurine and glycine content prevents high-fat, high-sucrose-induced obesity and improves plasma lipid profile in male C57BL/6J mice

    DEFF Research Database (Denmark)

    Tastesen, Hanne Sørup; Keenan, Alison H.; Madsen, Lise

    2014-01-01

    High-protein diets induce alterations in metabolism that may prevent diet-induced obesity. However, little is known as to whether different protein sources consumed at normal levels may affect diet-induced obesity and associated co-morbidities. We fed obesity-prone male C57BL/6J mice high-fat, high......-fed mice, but otherwise no changes in lean body mass were observed between the groups. Feed efficiency and apparent nitrogen digestibility were reduced in scallop-fed mice suggesting alterations in energy utilization and metabolism. Overnight fasted plasma triacylglyceride, non-esterified fatty acids......, glycerol and hydroxy-butyrate levels were significantly reduced, indicating reduced lipid mobilization in scallop-fed mice. The plasma HDL-to-total-cholesterol ratio was higher, suggesting increased reverse cholesterol transport or cholesterol clearance in scallop-fed mice in both fasted and non-fasted...

  17. Intestinal CREBH overexpression prevents high-cholesterol diet-induced hypercholesterolemia by reducing Npc1l1 expression

    Directory of Open Access Journals (Sweden)

    Takuya Kikuchi

    2016-11-01

    Conclusion: Intestinal CREBH regulates dietary cholesterol flow from the small intestine by controlling the expression of multiple intestinal transporters. We propose that intestinal CREBH could be a therapeutic target for hypercholesterolemia.

  18. Omega-3 polyunsaturated fatty acids and chronic stress-induced modulations of glutamatergic neurotransmission in the hippocampus.

    Science.gov (United States)

    Hennebelle, Marie; Champeil-Potokar, Gaëlle; Lavialle, Monique; Vancassel, Sylvie; Denis, Isabelle

    2014-02-01

    Chronic stress causes the release of glucocorticoids, which greatly influence cerebral function, especially glutamatergic transmission. These stress-induced changes in neurotransmission could be counteracted by increasing the dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Numerous studies have described the capacity of n-3 PUFAs to help protect glutamatergic neurotransmission from damage induced by stress and glucocorticoids, possibly preventing the development of stress-related disorders such as depression or anxiety. The hippocampus contains glucocorticoid receptors and is involved in learning and memory. This makes it particularly sensitive to stress, which alters certain aspects of hippocampal function. In this review, the various ways in which n-3 PUFAs may prevent the harmful effects of chronic stress, particularly the alteration of glutamatergic synapses in the hippocampus, are summarized. © 2014 International Life Sciences Institute.

  19. Apelin-APJ system is responsible for stress-induced increase in atrial natriuretic peptide expression in rat heart.

    Science.gov (United States)

    Izgut-Uysal, Vecihe Nimet; Acar, Nuray; Birsen, Ilknur; Ozcan, Filiz; Ozbey, Ozlem; Soylu, Hakan; Avci, Sema; Tepekoy, Filiz; Akkoyunlu, Gokhan; Yucel, Gultekin; Ustunel, Ismail

    2018-04-01

    The cardiovascular system is a primary target of stress and stress is the most important etiologic factor in cardiovascular diseases. Stressors increase expressions of atrial natriuretic peptide (ANP) and apelin in cardiac tissue. The aim of the present study was to investigate whether stress-induced apelin has an effect on the expression of ANP in the right atrium of rat heart. The rats were divided into the control, stress and F13A+stress groups. In the stress and F13A+stress groups, the rats were subjected to water immersion and restraint stress (WIRS) for 6h. In the F13A+stress group, apelin receptor antagonist F13A, was injected intravenously immediately before application of WIRS. The plasma samples were obtained for the measurement of corticosterone and atrial natriuretic peptide. The atrial samples were used for immunohistochemistry and western blot analysis. F13A administration prevented the rise of plasma corticosterone and ANP levels induced by WIRS. While WIRS application increased the expressions of apelin, HIF-1α and ANP in atrial tissue, while F13A prevented the stress-induced increase in the expression of HIF-1α and ANP. Stress-induced apelin induces ANP expression in atrial tissue and may play a role in cardiovascular homeostasis by increasing ANP expression under WIRS conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Melatonin inhibits snake venom and antivenom induced oxidative stress and augments treatment efficacy.

    Science.gov (United States)

    Sharma, Rachana D; Katkar, Gajanan D; Sundaram, Mahalingam S; Swethakumar, Basavarajaiah; Girish, Kesturu S; Kemparaju, Kempaiah

    2017-05-01

    Snakebite is a neglected health hazard. Its patho-physiology has largely been focused on systemic and local toxicities; whereas, venom and antivenom induced oxidative stress has long been ignored. Antivenom therapy although neutralizes venom lethality and saves many lives, remains ineffective against oxidative stress. This prompted us to complement antivenom with an antioxidant molecule melatonin that would protect against oxidative stress and increase the efficacy of the existing snakebite therapy. Here we show that D. russelli and E. carinatus venoms induce strong oxidative stress that persists even after antivenom administration in mice model. Additionally, antivenoms also induce oxidative stress. Polyvalent antivenom induce more oxidative stress than monovalent antivenom. Strikingly, antivenom and melatonin together not only inhibit venom and antivenom induced oxidative stress but also significantly reduce the neutralizing antivenom dose. This study provides a therapeutic potential for enhancing the existing snakebite therapy. The combined treatment of antivenom+melatonin would prevent the upsurge of oxidative stress as well as minimize the antivenom load. Thus the investigation offers immense scope for physicians and toxinologists to reinvestigate, design new strategies and think beyond the conventional mode of antivenom therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Cholesterol oxidized products in foods: potential health hazards and the role of antioxidants in prevention

    Directory of Open Access Journals (Sweden)

    Nieto, Susana

    2004-09-01

    Full Text Available Cholesterol is a molecule with a double bond in its structure, and therefore it is susceptible to oxidation leading to the formation of oxysterols. These oxidation products are found in many commonly consumed foods and are formed during their manufacture and/or processing. Concern about the consumption of oxysterols arises from the potentially cytotoxic, mutagenic, atherogenic, and possibly carcinogenic effects of some of them. Eggs and egg-derived products are the main dietary sources of oxysterols. Thermally processed milk and milk-derived products are also another source of oxysterols in our diet. Fried meats, and other miscellaneous foods, such as French fried potatoes, when prepared using vegetable/animal frying oil, are another important source of oxysterols in the western diet. Efforts to prevent or to reduce cholesterol oxidation are directed to the application of antioxidants of either synthetic or natural origin. Antioxidants cannot only inhibit triglyceride oxidation, but some of them can also inhibit cholesterol oxidation. Among synthetic antioxidants, 2,6-di-ter tiarybutyl-4-methylphenol (BHT and ter tiary butylhydroquinone (TBHQ , can eff icient ly inhibit the thermal-induced oxidation of cholesterol. Among natural antioxidants, alpha- and gamma-tocopherol, rosemary extracts, and flavonoid quercetin, show the strongest inhibitory action against cholesterol oxidation.El colesterol es una molécula con un doble enlace en su estructura; por lo tanto es susceptible a la oxidación y su transformación en oxiesteroles. Estos productos de oxidación se encuentran en gran diversidad de alimentos y se forman durante la manufactura y procesamiento. Algunos de los oxiesteroles son potencialmente citotóxicos, mutagénicos, aterogénicos y carcinogénicos. Los huevos y productos derivados del huevo constituyen la principal fuente en la dieta de oxiesteroles. También se encuentran oxiesteroles en derivados lácteos y leche sometida a altas

  2. Cholesterol and related sterols autoxidation.

    Science.gov (United States)

    Zerbinati, Chiara; Iuliano, Luigi

    2017-10-01

    Cholesterol is a unique lipid molecule providing the building block for membranes, hormones, vitamin D and bile acid synthesis. Metabolism of cholesterol involves several enzymes acting on the sterol nucleus or the isooctyl tail. In the recent years, research interest has been focused on oxysterols, cholesterol derivatives generated by the addition of oxygen to the cholesterol backbone. Oxysterols can be produced enzymatically or by autoxidation. Autoxidation of cholesterol proceeds through type I or type II mechanisms. Type I autoxidation is initiated by free radical species, such as those arising from the superoxide/hydrogen peroxide/hydroxyl radical system. Type II autoxidation occurs stoichiometrically by non-radical highly reactive oxygen species such as singlet oxygen, HOCl, and ozone. The vulnerability of cholesterol towards high reactive species has raised considerable interest for mechanistic studies and for the potential biological activity of oxysterols, as well as for the use of oxysterols as biomarkers for the non-invasive study of oxidative stress in vivo. Copyright © 2017. Published by Elsevier Inc.

  3. Exercise-induced oxidative stress and antioxidant enzyme activity in type 2 diabetic patients with and without diastolic dysfunction and hypertension

    Directory of Open Access Journals (Sweden)

    Kostić Nada

    2009-01-01

    increase of GSH-Px activity (47.10±7.37 vs 54.52±11.97 U/g Hb; p<0.01. Conclusion. Elevated enzyme levels are associated with exercise in type 2 diabetic patients. We suggest that it could be a compensatory mechanism to prevent free radical tissue damage. We hypothesize that a physical training programme induces the enhancement of muscular and liver antioxidant enzymes and reduces the oxidative stress.

  4. Protective effect of Curcuma longa L. extract on CCl4-induced acute hepatic stress.

    Science.gov (United States)

    Lee, Geum-Hwa; Lee, Hwa-Young; Choi, Min-Kyung; Chung, Han-Wool; Kim, Seung-Wook; Chae, Han-Jung

    2017-02-01

    The Curcuma longa L. (CLL) rhizome has long been used to treat patients with hepatic dysfunction. CLL is a member of the ginger family of spices that are widely used in China, India, and Japan, and is a common spice, coloring, flavoring, and traditional medicine. This study was performed to evaluate the hepatoprotective activity of CLL extract and its active component curcumin in an acute carbon tetrachloride (CCl 4 )-induced liver stress model. Acute hepatic stress was induced by a single intraperitoneal injection of CCl 4 (0.1 ml/kg body weight) in rats. CLL extract was administered once a day for 3 days at three dose levels (100, 200, and 300 mg/kg/day) and curcumin was administered once a day at the 200 mg/kg/day. We performed alanine transaminase (ALT) and aspartate transaminase (AST). activity analysis and also measured total lipid, triglyceride, and cholesterol levels, and lipid peroxidation. At 100 g CLL, the curcuminoid components curcumin (901.63 ± 5.37 mg/100 g), bis-demethoxycurcumin (108.28 ± 2.89 mg/100 g), and demethoxycurcumin (234.85 ± 1.85 mg/100 g) were quantified through high liquid chromatography analysis. In CCl 4 -treated rats, serum AST and ALT levels increased 2.1- and 1.2-fold compared with the control. AST but not ALT elevation induced by CCl 4 was significantly alleviated in CLL- and curcumin-treated rats. Peroxidation of membrane lipids in the liver was significantly prevented by CLL (100, 200, and 300 mg/kg/day) on tissue lipid peroxidation assay and immunostaining with anti-4HNE antibody. We found that CLL extract and curcumin exhibited significant protection against liver injury by improving hepatic superoxide dismutase (p < 0.05) and glutathione peroxidase activity, and glutathione content in the CCl 4 -treated group (p < 0.05), leading to a reduced lipid peroxidase level. Our data suggested that CLL extract and curcumin protect the liver from acute CCl 4 -induced injury in a rodent model by suppressing

  5. Low dose radiation prevents doxorubicin-induced cardiotoxicity.

    Science.gov (United States)

    Jiang, Xin; Hong, Yaqiong; Zhao, Di; Meng, Xinxin; Zhao, Lijing; Du, Yanwei; Wang, Zan; Zheng, Yan; Cai, Lu; Jiang, Hongyu

    2018-01-02

    This study aimed to develop a novel and non-invasive approach, low-dose radiation (LDR, 75 mGy X-rays), to prevent doxorubicin (DOX)-induced cardiotoxicity. BALB/c mice were randomly divided into five groups, Control, LDR (a single exposure), Sham (treated same as LDR group except for irradiation), DOX (a single intraperitoneal injection of DOX at 7.5 mg/kg), and LDR/DOX (received LDR and 72 h later received DOX). Electrocardiogram analysis displayed several kinds of abnormal ECG profiles in DOX-treated mice, but less in LDR/DOX group. Cardiotoxicity indices included histopathological changes, oxidative stress markers, and measurements of mitochondrial membrane permeability. Pretreatment of DOX group with LDR reduced oxidative damages (reactive oxygen species formation, protein nitration, and lipid peroxidation) and increased the activities of antioxidants (superoxide dismutase and glutathione peroxidase) in the heart of LDR/DOX mice compared to DOX mice. Pretreatment of DOX-treated mice with LDR also decreased DOX-induced cardiac cell apoptosis (TUNEL staining and cleaved caspase-3) and mitochondrial apoptotic pathway (increased p53, Bax, and caspase-9 expression and decreased Bcl2 expression and ΔΨm dissipation). These results suggest that LDR could induce adaptation of the heart to DOX-induced toxicity. Cardiac protection by LDR may attribute to attenuate DOX-induced cell death via suppressing mitochondrial-dependent oxidative stress and apoptosis signaling.

  6. NAD+-Carrying Mesoporous Silica Nanoparticles Can Prevent Oxidative Stress-Induced Energy Failures of Both Rodent Astrocytes and PC12 Cells

    Science.gov (United States)

    Chen, Heyu; Wang, Yao; Zhang, Jixi; Ma, Yingxin; Wang, Caixia; Zhou, Ying; Gu, Hongchen; Ying, Weihai

    2013-01-01

    Aim To test the hypothesis that NAD+-carrying mesoporous silica nanoparticles (M-MSNs@NAD+) can effectively deliver NAD+ into cells to produce cytoprotective effects. Methods & Materials NAD+ was incorporated into M-MSNs. Primary rat astrocyte cultures and PC12 cells were treated with H2O2, followed by post-treatment with M-MSNs@NAD+. After various durations of the post-treatment, intracellular NAD+ levels, intracellular ATP levels and lactate dehydrogenase (LDH) release were determined. Results & Discussion M-MSNs can be effectively loaded with NAD+. The M-MSNs@NAD+ can significantly attenuate H2O2-induced NAD+ and ATP decreases in both astrocyte cultures and PC12 cells. M-MSNs@NAD+ can also partially prevent the H2O2-induced LDH release from both astrocyte cultures and PC12 cells. In contrast, the NAD+ that is spontaneously released from the M-MSNs@NAD+ is insufficient to prevent the H2O2-induced damage. Conclusions Our study has suggested the first approach that can effectively deliver NAD+ into cells, which provides an important basis both for elucidating the roles of intracellular NAD+ in biological functions and for therapeutic applications of NAD+. Our study has also provided the first direct evidence demonstrating a key role of NAD+ depletion in oxidative stress-induced ATP decreases. PMID:24040179

  7. Polyphenols isolated from virgin coconut oil attenuate cadmium-induced dyslipidemia and oxidative stress due to their antioxidant properties and potential benefits on cardiovascular risk ratios in rats.

    Science.gov (United States)

    Famurewa, Ademola Clement; Ejezie, Fidelis Ebele

    2018-01-01

    Literature has confirmed the pathogenic role of cadmium (Cd) and its exposure in the induction of dyslipidemia implicated in the development and increasing incidence of cardiovascular diseases. The current study explored whether polyphenolics isolated from virgin coconut oil (VCO) prevent Cd-induced dyslipidemia and investigate the underlying mechanism of action, in rats. Rats were pretreated with VCO polyphenols (10, 20 and 50 mg/kg body weight; orally) 2 weeks prior to concurrent Cd administration (5 mg/kg) for 5 weeks. Subsequently, serum concentrations of lipid and lipoprotein cholesterol and cardiovascular risk ratios were determined. Hepatic activities of superoxide dismutase (SOD) and catalase (CAT) as well as reduced glutathione (GSH) and malondialdehyde (MDA) contents were analyzed. Sub-chronic Cd administration significantly increased the serum levels of total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol while markedly reduced high density lipoprotein cholesterol. Hepatic activities of SOD and CAT as well as GSH content were suppressed by Cd, whereas MDA level was obviously increased. The co-administration of VCO polyphenol with Cd remarkably restored lipid profile and cardiovascular risk ratios and stabilized antioxidant defense systems comparable to control group. This is the first study presenting that polyphenols isolated from VCO prevent Cd-induced lipid abnormalities and cardiovascular risk ratios by improving antioxidant defense systems.

  8. Polyphenols isolated from virgin coconut oil attenuate cadmium-induced dyslipidemia and oxidative stress due to their antioxidant properties and potential benefits on cardiovascular risk ratios in rats

    Directory of Open Access Journals (Sweden)

    Ademola Clement Famurewa

    2017-12-01

    Full Text Available Objective: Literature has confirmed the pathogenic role of cadmium (Cd and its exposure in the induction of dyslipidemia implicated in the development and increasing incidence of cardiovascular diseases. The current study explored whether polyphenolics isolated from virgin coconut oil (VCO prevent Cd-induced dyslipidemia and investigate the underlying mechanism of action, in rats. Materials and Methods: Rats were pretreated with VCO polyphenols (10, 20 and 50 mg/kg body weight; orally 2 weeks prior to concurrent Cd administration (5 mg/kg for 5 weeks. Subsequently, serum concentrations of lipid and lipoprotein cholesterol and cardiovascular risk ratios were determined. Hepatic activities of superoxide dismutase (SOD and catalase (CAT as well as reduced glutathione (GSH and malondialdehyde (MDA contents were analyzed. Results: Sub-chronic Cd administration significantly increased the serum levels of total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol while markedly reduced high density lipoprotein cholesterol. Hepatic activities of SOD and CAT as well as GSH content were suppressed by Cd, whereas MDA level was obviously increased. The co-administration of VCO polyphenol with Cd remarkably restored lipid profile and cardiovascular risk ratios and stabilized antioxidant defense systems comparable to control group. Conclusion: This is the first study presenting that polyphenols isolated from VCO prevent Cd-induced lipid abnormalities and cardiovascular risk ratios by improving antioxidant defense systems.

  9. How to Prevent Heart Disease: MedlinePlus Health Topic

    Science.gov (United States)

    ... and your heart (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get How to Prevent ... your heart Stress and your heart Related Health Topics Blood Thinners Cholesterol Heart Diseases Heart Health Tests ...

  10. Regulation of biliary cholesterol secretion and reverse cholesterol transport

    NARCIS (Netherlands)

    Dikkers, Arne

    2016-01-01

    According to the World Health Organization the number one cause of death throughout the world is cardiovascular disease. Therefore, there is an urgent need for new therapeutic strategies to prevent and treat cardiovascular disease. One possible way is to target the HDL-driven reverse cholesterol

  11. Transdermal deferoxamine prevents pressure-induced diabetic ulcers.

    Science.gov (United States)

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W; Maan, Zeshaan N; Rennert, Robert C; Inayathullah, Mohammed; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V; Whitmore, Arnetha J; Walmsley, Graham G; Galvez, Michael G; Whittam, Alexander J; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C

    2015-01-06

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.

  12. Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Xueqi; Huang, Shengbin; Yu, Qing [Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS, 66047 (United States); State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 (China); Yu, Haiyang [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 (China); Yan, Shirley ShiDu, E-mail: shidu@ku.edu [Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS, 66047 (United States)

    2015-12-25

    Osteoblast dysfunction, induced by oxidative stress, plays a critical role in the pathophysiology of osteoporosis. However, the underlying mechanisms remain unclarified. Imbalance of mitochondrial dynamics has been closely linked to oxidative stress. Here, we reveal an unexplored role of dynamic related protein 1(Drp1), the major regulator in mitochondrial fission, in the oxidative stress-induced osteoblast injury model. We demonstrate that levels of phosphorylation and expression of Drp1 significantly increased under oxidative stress. Blockade of Drp1, through pharmaceutical inhibitor or gene knockdown, significantly protected against H{sub 2}O{sub 2}-induced osteoblast dysfunction, as shown by increased cell viability, improved cellular alkaline phosphatase (ALP) activity and mineralization and restored mitochondrial function. The protective effects of blocking Drp1 in H{sub 2}O{sub 2}-induced osteoblast dysfunction were evidenced by increased mitochondrial function and suppressed production of reactive oxygen species (ROS). These findings provide new insights into the role of the Drp1-dependent mitochondrial pathway in the pathology of osteoporosis, indicating that the Drp1 pathway may be targetable for the development of new therapeutic approaches in the prevention and the treatment of osteoporosis. - Highlights: • Oxidative stress is an early pathological event in osteoporosis. • Imbalance of mitochondrial dynamics are linked to oxidative stress in osteoporosis. • The role of the Drp1-dependent mitochondrial pathway in osteoporosis.

  13. The usefulness of information on HDL-cholesterol: potential pitfalls of conventional assumptions

    Directory of Open Access Journals (Sweden)

    Furberg Curt D

    2001-05-01

    Full Text Available Abstract Treatment decisions related to disease prevention are often based on two conventional and related assumptions. First, an intervention-induced change in a surrogate marker (such as high-density lipoprotein [HDL]-cholesterol in the desired direction translates into health benefits (such as reduction in coronary events. Second, it is unimportant which interventions are used to alter surrogate markers, since an intervention benefit is independent of the means by which it is achieved. The scientific foundation for these assumptions has been questioned. In this commentary, the appropriateness of relying on low levels of HDL-cholesterol for treatment decisions is reviewed. The Veterans Affairs - HDL-Cholesterol Intervention Trial (VA-HIT investigators recently reported that only 23% of the gemfibrozil-induced relative reduction in risk of coronary events observed in the trial could be explained by changes in HDL-cholesterol between baseline and the 1-year visit. Thus, 77% of the health benefit to the participants was unexplained. Other possible explanations are that gemfibrozil has multiple mechanisms of action, disease manifestations are multifactorial, and laboratory measurements of HDL-cholesterol are imprecise. The wisdom of relying on levels and changes in surrogate markers such as HDL-cholesterol to make decisions about treatment choices should questioned. It seems better to rely on direct evidence of health benefits and to prescribe specific interventions that have been shown to reduce mortality and morbidity. Since extrapolations based on surrogate markers may not be in patients' best interest, the practice of medicine ought to be evidence-based.

  14. Single fluoxetine treatment before but not after stress prevents stress-induced hippocampal long-term depression and spatial memory retrieval impairment in rats

    Science.gov (United States)

    Han, Huili; Dai, Chunfang; Dong, Zhifang

    2015-01-01

    A growing body of evidence has shown that chronic treatment with fluoxetine, a widely prescribed medication for treatment of depression, can affect synaptic plasticity in the adult central nervous system. However, it is not well understood whether acute fluoxetine influences synaptic plasticity, especially on hippocampal CA1 long-term depression (LTD), and if so, whether it subsequently impacts hippocampal-dependent spatial memory. Here, we reported that LTD facilitated by elevated-platform stress in hippocampal slices was completely prevented by fluoxetine administration (10 mg/kg, i.p.) 30 min before stress. The LTD was not, however, significantly inhibited by fluoxetine administration immediately after stress. Similarly, fluoxetine incubation (10 μM) during electrophysiological recordings also displayed no influence on the stress-facilitated LTD. In addition, behavioral results showed that a single fluoxetine treatment 30 min before but not after acute stress fully reversed the impairment of spatial memory retrieval in the Morris water maze paradigm. Taken together, these results suggest that acute fluoxetine treatment only before, but not after stress, can prevent hippocampal CA1 LTD and spatial memory retrieval impairment caused by behavioral stress in adult animals. PMID:26218751

  15. Basolateral cholesterol depletion alters Aquaporin-2 post-translational modifications and disrupts apical plasma membrane targeting.

    Science.gov (United States)

    Moeller, Hanne B; Fuglsang, Cecilia Hvitfeldt; Pedersen, Cecilie Nøhr; Fenton, Robert A

    2018-01-01

    Apical plasma membrane accumulation of the water channel Aquaporin-2 (AQP2) in kidney collecting duct principal cells is critical for body water homeostasis. Posttranslational modification (PTM) of AQP2 is important for regulating AQP2 trafficking. The aim of this study was to determine the role of cholesterol in regulation of AQP2 PTM and in apical plasma membrane targeting of AQP2. Cholesterol depletion from the basolateral plasma membrane of a collecting duct cell line (mpkCCD14) using methyl-beta-cyclodextrin (MBCD) increased AQP2 ubiquitylation. Forskolin, cAMP or dDAVP-mediated AQP2 phosphorylation at Ser269 (pS269-AQP2) was prevented by cholesterol depletion from the basolateral membrane. None of these effects on pS269-AQP2 were observed when cholesterol was depleted from the apical side of cells, or when MBCD was applied subsequent to dDAVP stimulation. Basolateral, but not apical, MBCD application prevented cAMP-induced apical plasma membrane accumulation of AQP2. These studies indicate that manipulation of the cholesterol content of the basolateral plasma membrane interferes with AQP2 PTM and subsequently regulated apical plasma membrane targeting of AQP2. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Luo, Di-xian; Xia, Cheng-lai; Li, Jun-mu; Xiong, Yan; Yuan, Hao-yu; TANG, Zhen-Wang; Zeng, Yixin; Liao, Duan-fang

    2010-01-01

    Research highlights: → Vertical static pressure accelerates ox-LDL-induced cholesterol accumulation in cultured vascular smooth muscle cells. → Static pressure induces SREBP-1 activation. → Static pressure downregulates the expressions of caveolin-1 by activating SREBP-1. → Static pressure also downregulates the transcription of ABCA1 by activating SREBP-1. → Static pressure increases ox-LDL-induced cholesterol accumulation by SREBP-1-mediated caveolin-1 downregulation in vascular smooth muscle cells cultured in vitro. -- Abstract: Objective: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. Methods: Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different static pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. Results: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 ± 2.8 mg/g, 31.8 ± 0.7 mg/g, 92.3 ± 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 ± 9.4 mg/g, 235.9 ± 3.0 mg/g, 386.7 ± 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were upregulated. Conclusion: Static

  17. Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Di-xian, E-mail: luodixian_2@163.com [Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha 410083, Hunan (China); Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); First People' s Hospital of Chenzhou City, Chenzhou 423000, Hunan (China); Xia, Cheng-lai [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Department of Pharmacy, Third Affiliated Hospital Medical College of Guangzhou, Guangzhou 510150, Guangdong (China); Li, Jun-mu [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Xiong, Yan [Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha 410083, Hunan (China); Yuan, Hao-yu [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Lusong Center for Disease Control and Prevention, Zhuzhou 412000, Hunan (China); TANG, Zhen-Wang; Zeng, Yixin [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Liao, Duan-fang, E-mail: dfliao66@yahoo.com.cn [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Department of Traditional Chinese Diagnostics, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 420108, Hunan (China)

    2010-12-03

    Research highlights: {yields} Vertical static pressure accelerates ox-LDL-induced cholesterol accumulation in cultured vascular smooth muscle cells. {yields} Static pressure induces SREBP-1 activation. {yields} Static pressure downregulates the expressions of caveolin-1 by activating SREBP-1. {yields} Static pressure also downregulates the transcription of ABCA1 by activating SREBP-1. {yields} Static pressure increases ox-LDL-induced cholesterol accumulation by SREBP-1-mediated caveolin-1 downregulation in vascular smooth muscle cells cultured in vitro. -- Abstract: Objective: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. Methods: Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different static pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. Results: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 {+-} 2.8 mg/g, 31.8 {+-} 0.7 mg/g, 92.3 {+-} 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 {+-} 9.4 mg/g, 235.9 {+-} 3.0 mg/g, 386.7 {+-} 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were

  18. Valsartan Protects Against Contrast-Induced Acute Kidney Injury in Rats by Inhibiting Endoplasmic Reticulum Stress-Induced Apoptosis.

    Science.gov (United States)

    Sun, Yan; Peng, Ping-An; Ma, Yue; Liu, Xiao-Li; Yu, Yi; Jia, Shuo; Xu, Xiao-Han; Wu, Si-Jing; Zhou, Yu-Jie

    2017-01-01

    Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the administration of iodinated contrast media (CM) for diagnostic and interventional cardiovascular procedures and is associated with substantial morbidity and mortality. While the preventative measures can mitigate the risk of CI-AKI, there remains a need for novel and effective therapeutic approaches. The pathogenesis of CI-AKI is complex and not completely understood. CM-induced renal tubular cell apoptosis caused by the activation of endoplasmic reticulum (ER) stress is involved in CIAKI. We previously demonstrated that valsartan alleviated CM-induced human renal tubular cell apoptosis by inhibiting ER stress in vitro. However, the nephroprotective effect of valsartan on CI-AKI in vivo has not been investigated. Therefore, the aim of this study was to explore the protective effect of valsartan in a rat model of CI-AKI by measuring the amelioration of renal damage and the changes in ER stressrelated biomarkers. Our results showed that the radiocontrast agent meglumine diatrizoate caused significant renal insufficiency, renin-angiotensin system (RAS) activation, and renal tubular apoptosis by triggering ER stress through activation of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), caspase 12, CCAAT/enhancer-binding protein-homologous protein (CHOP) and c-Jun N-terminal protein kinase (JNK) (Pvalsartan significantly alleviated renal dysfunction, pathological injury, and apoptosis along with the inhibition of ER stressrelated biomarkers (PValsartan could protect against meglumine diatrizoate-induced kidney injury in rats by inhibiting the ER stress-induced apoptosis, making it a promising strategy for preventing CI-AKI. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

    Science.gov (United States)

    Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

    2016-11-15

    Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Carvedilol, a third-generation β-blocker prevents oxidative stress-induced neuronal death and activates Nrf2/ARE pathway in HT22 cells

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang, Ying [Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Chen, Ziwei [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Tan, Min [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Department of Traditional Chinese Medicine Chemistry, College of Chinese Materia Madica, Guangzhou University of Chinese Medicine, Guangzhou 510006 (China); Liu, Anmin [Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Chen, Meihui [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Liu, Jun [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Pi, Rongbiao, E-mail: pirb@mail.sysu.edu.cn [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Fang, Jianpei, E-mail: jpf2005@163.com [Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China)

    2013-11-29

    Highlights: •Carvedilol significantly prevented oxidative stress-induced cell death. •Carvedilol significantly decreased the production of ROS. •Carvedilol activated Nrf2/ARE pathway. •Carvedilol increased the protein levels of HO-1 and NQO-1. -- Abstract: Carvedilol, a nonselective β-adrenoreceptor blocker with pleiotropic activities has been shown to exert neuroprotective effect due to its antioxidant property. However, the neuroprotective mechanism of carvedilol is still not fully uncovered. Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. Here we investigated the effect of carvedilol on oxidative stress-induced cell death (glutamate 2 mM and H{sub 2}O{sub 2} 600 μM) and the activity of Nrf2/ARE pathway in HT22 hippocampal cells. Carvedilol significantly increased cell viability and decreased ROS in HT22 cells exposed to glutamate or H{sub 2}O{sub 2}. Furthermore, carvedilol activated the Nrf2/ARE pathway in a concentration-dependent manner, and increased the protein levels of heme oxygenase-1(HO-1) and NAD(P)H quinone oxidoreductase-1(NQO-1), two downstream factors of the Nrf2/ARE pathway. Collectively, our results indicate that carvedilol protects neuronal cell against glutamate- and H{sub 2}O{sub 2}-induced neurotoxicity possibly through activating the Nrf2/ARE signaling pathway.

  1. Antioxidant effect of sericin in brain and peripheral tissues of oxidative stress induced hypercholesterolemic rats

    Directory of Open Access Journals (Sweden)

    Meetali Deori

    2016-09-01

    Full Text Available This study evaluated the antioxidant effect of crude sericin extract (CSE from Antheraea assamenisis (Aa in high cholesterol fed rats. Investigation was conducted by administering graded oral dose of 0.25 and 0.5 gm/kg body weight (b.w./day of CSE for a period of 28 days. Experiments were conducted in 30 rats and were divided into five groups: normal control (NC, high cholesterol fed (HCF, HCF + 0.065 gm/kg b.w./day fenofibrate (FF, HCF + sericin 0.25 gm/kg b.w./day (LSD and HCF + sericin 0.5 gm/kg b.w./day (HSD. In brain, heart, liver, serum and kidney homogenates nitric oxide (NO, thiobarbituric acid reactive substances (TBARS, protein carbonyl content (PCC, superoxide dismutase (SOD, reduced glutathione (GSH was measured. LSD treatment prevented the alterations in GSH and PCC levels in hypercholesterolemic (HyC brain tissue homogenates of rats. CSE lowers the serum total cholesterol level in HyC rats by promoting fecal cholesterol (FC excretion. CSE increases FC level by promoting inhibition of cholesterol absorption in intestine. The endogenous antioxidant reduced significantly and the oxidative stress (OS marker TBARS level increases significantly in the peripheral tissue of HCF rats. However, the administration of LSD and HSD exhibited a good antioxidant activity by reducing the TBARS level and increasing the endogenous antioxidant in peripheral tissue. In addition, a histological examination revealed loss of normal liver and kidney architecture in cholesterol fed rats which were retained in sericin treated groups. The findings of this study suggested that CSE improves hypercholesterolemia in rats fed a HyC diet. Clinical relevance of this effect of CSE seems worthy of further studies.

  2. Prevention of stress-impaired fear extinction through neuropeptide s action in the lateral amygdala.

    Science.gov (United States)

    Chauveau, Frédéric; Lange, Maren Denise; Jüngling, Kay; Lesting, Jörg; Seidenbecher, Thomas; Pape, Hans-Christian

    2012-06-01

    Stressful and traumatic events can create aversive memories, which are a predisposing factor for anxiety disorders. The amygdala is critical for transforming such stressful events into anxiety, and the recently discovered neuropeptide S transmitter system represents a promising candidate apt to control these interactions. Here we test the hypothesis that neuropeptide S can regulate stress-induced hyperexcitability in the amygdala, and thereby can interact with stress-induced alterations of fear memory. Mice underwent acute immobilization stress (IS), and neuropeptide S and a receptor antagonist were locally injected into the lateral amygdala (LA) during stress exposure. Ten days later, anxiety-like behavior, fear acquisition, fear memory retrieval, and extinction were tested. Furthermore, patch-clamp recordings were performed in amygdala slices prepared ex vivo to identify synaptic substrates of stress-induced alterations in fear responsiveness. (1) IS increased anxiety-like behavior, and enhanced conditioned fear responses during extinction 10 days after stress, (2) neuropeptide S in the amygdala prevented, while an antagonist aggravated, these stress-induced changes of aversive behaviors, (3) excitatory synaptic activity in LA projection neurons was increased on fear conditioning and returned to pre-conditioning values on fear extinction, and (4) stress resulted in sustained high levels of excitatory synaptic activity during fear extinction, whereas neuropeptide S supported the return of synaptic activity during fear extinction to levels typical of non-stressed animals. Together these results suggest that the neuropeptide S system is capable of interfering with mechanisms in the amygdala that transform stressful events into anxiety and impaired fear extinction.

  3. Phaleria macrocarpa Boerl. (Thymelaeaceae Leaves Increase SR-BI Expression and Reduce Cholesterol Levels in Rats Fed a High Cholesterol Diet

    Directory of Open Access Journals (Sweden)

    Yosie Andriani

    2015-03-01

    Full Text Available In vitro and in vivo studies of the activity of Phaleria macrocarpa Boerl (Thymelaeaceae leaves against the therapeutic target for hypercholesterolemia were done using the HDL receptor (SR-BI and hypercholesterolemia-induced Sprague Dawley rats. The in vitro study showed that the active fraction (CF6 obtained from the ethyl acetate extract (EMD and its component 2',6',4-trihydroxy-4'-methoxybenzophenone increased the SR-BI expression by 95% and 60%, respectively. The in vivo study has proven the effect of EMD at 0.5 g/kgbw dosage in reducing the total cholesterol level by 224.9% and increasing the HDL cholesterol level by 157% compared to the cholesterol group. In the toxicity study, serum glutamate oxalate transaminase (SGOT and serum glutamate pyruvate transaminase (SGPT activity were observed to be at normal levels. The liver histology also proved no toxicity and abnormalities in any of the treatment groups, so it can be categorized as non-toxic to the rat liver. The findings taken together show that P. macrocarpa leaves are safe and suitable as an alternative control and prevention treatment for hypercholesterolemia in Sprague Dawley rats.

  4. Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

    Science.gov (United States)

    Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

    2017-04-01

    Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Isoflavone and Protein Constituents of Lactic Acid-Fermented Soy Milk Combine to Prevent Dyslipidemia in Rats Fed a High Cholesterol Diet

    Science.gov (United States)

    Kobayashi, Maki; Egusa, Shintaro; Fukuda, Mitsuru

    2014-01-01

    A high cholesterol diet induces dyslipidemia. This study investigated whether isoflavone aglycones in lactic acid-fermented soy milk (LFS) improve lipid metabolism in rats fed a high cholesterol diet. Male Sprague-Dawley rats aged seven weeks were fed an AIN-93G diet, a 1% cholesterol diet (a high cholesterol diet), a high-cholesterol diet containing 4% isoflavone extract of LFS (LFS extract diet), a high-cholesterol diet containing 19.4% ethanol-washed LFS (ethanol-washed LFS diet, isoflavone-poor diet), or a high cholesterol diet containing 23.2% intact LFS (intact LFS diet) for five weeks. The plasma total cholesterol (TC) level was increased in the rats fed the LFS extract diet compared with those fed the high cholesterol diet. The TC level was decreased by the intact LFS and ethanol-washed LFS diets. The cholesterol-lowering effect was stronger in the rats fed the intact LFS diet than those fed the ethanol-washed LFS diet. The plasma triglyceride (TG) level was unchanged in the rats fed the LFS extract diet, but it decreased in rats fed the intact LFS and ethanol-washed LFS diets. Although, compared with the high cholesterol diet, the LFS extract and ethanol-washed LFS diets did not reduce hepatic cholesterol and TG, both levels were remarkably lowered by the intact LFS diet. These results suggest that the improvement in lipid metabolism of rats fed a high-cholesterol diet containing LFS isoflavone aglycones is not due to an independent effect but due to a cooperative effect with soy protein. PMID:25514389

  6. Isoflavone and Protein Constituents of Lactic Acid-Fermented Soy Milk Combine to Prevent Dyslipidemia in Rats Fed a High Cholesterol Diet

    Directory of Open Access Journals (Sweden)

    Maki Kobayashi

    2014-12-01

    Full Text Available A high cholesterol diet induces dyslipidemia. This study investigated whether isoflavone aglycones in lactic acid-fermented soy milk (LFS improve lipid metabolism in rats fed a high cholesterol diet. Male Sprague-Dawley rats aged seven weeks were fed an AIN-93G diet, a 1% cholesterol diet (a high cholesterol diet, a high-cholesterol diet containing 4% isoflavone extract of LFS (LFS extract diet, a high-cholesterol diet containing 19.4% ethanol-washed LFS (ethanol-washed LFS diet, isoflavone-poor diet, or a high cholesterol diet containing 23.2% intact LFS (intact LFS diet for five weeks. The plasma total cholesterol (TC level was increased in the rats fed the LFS extract diet compared with those fed the high cholesterol diet. The TC level was decreased by the intact LFS and ethanol-washed LFS diets. The cholesterol-lowering effect was stronger in the rats fed the intact LFS diet than those fed the ethanol-washed LFS diet. The plasma triglyceride (TG level was unchanged in the rats fed the LFS extract diet, but it decreased in rats fed the intact LFS and ethanol-washed LFS diets. Although, compared with the high cholesterol diet, the LFS extract and ethanol-washed LFS diets did not reduce hepatic cholesterol and TG, both levels were remarkably lowered by the intact LFS diet. These results suggest that the improvement in lipid metabolism of rats fed a high-cholesterol diet containing LFS isoflavone aglycones is not due to an independent effect but due to a cooperative effect with soy protein.

  7. Omega-3 Polyunsaturated Fatty Acids Attenuate Radiation-induced Oxidative Stress and Organ Dysfunctions in Rats

    International Nuclear Information System (INIS)

    Abdel Aziz, N.; Yacoub, S.F.

    2013-01-01

    The Aim of the present study was to determine the possible protective effect of omega-3 polyunsaturated fatty acids (omega-3 PUFA) against radiation-induced oxidative stress associated with organ dysfunctions. Omega-3 PUFA was administered by oral gavages to male albino rats at a dose of 0.4 g/ kg body wt daily for 4 weeks before whole body γ-irradiation with 4Gy. Significant increase of serum lipid peroxidation end product as malondialdehyde (MDA) along with the reduction in blood glutathione (GSH) content, superoxide dismutase (SOD) and glutathione peroxidase (GPX) enzyme activities were recorded on 3rd and 8th days post-irradiation. Oxidative stress was associated with a significant increase in lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) enzyme activities, markers of heart damage, significant increases in uric acid, urea and creatinine levels, markers of kidney damage, significant increases of alkaline phosphatase (ALP) and transaminases (ALT and AST) activities, markers of liver damage. Moreover significant increases in total cholesterol and triglycerides levels were recorded. Omega-3 PUFA administration pre-irradiation significantly attenuated the radiation-induced oxidative stress and organ dysfunctions tested in this study. It could be concluded that oral supplementation of omega-3 PUFA before irradiation may afford protection against radiation-induced oxidative stress and might preserve the integrity of tissue functions of the organs under investigations.

  8. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    Directory of Open Access Journals (Sweden)

    Magdalena Cristóbal-García

    2015-01-01

    Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  9. Stress corrosion cracking prevention using solar electricity

    International Nuclear Information System (INIS)

    Harijan, K.; Uqaaili, M.A; Mirani, M.

    2004-01-01

    Metallic structures exposed to soil and water naturally experience corrosion due to electrolytic action. These structures are also subjected to sustained tensile stresses. The combined effects of corrosion and stress results stress corrosion cracking (SCC). Removal of either of these i.e. stress or corrosion prevents SCC. The cathodic protection (CP) prevents corrosion, and hence prevents stress corrosion. Solar Photo voltaic (PV) generated electricity can be best external power source for CP systems especially in remote areas. This paper presents CP system using solar PV generated electricity as an external power source for prevention of SCC of metallic structures. The paper also compares CP systems using solar electricity with those of CP systems using conventional electricity. The paper concludes that a solar electricity power system provides a reliable solution for powering CP stations especially in remote areas, enables the placing of CP units in any location, and thus ensures optimal current distribution for the exact protection requirements. The paper also concludes that solar electricity CP systems are well suited for SCC protection of metallic structures especially in remote areas of an energy deficit country like Pakistan. (author)

  10. 3-Keto-1,5-bisphosphonates Alleviate Serum-Oxidative Stress in the High-fat Diet Induced Obesity in Rats.

    Science.gov (United States)

    Lahbib, Karima; Aouani, Iyadh; Cavalier, Jean-François; Touil, Soufiane

    2015-09-01

    Obesity has become a leading global health problem owing to its strong association with a high incidence of oxidative stress. Many epidemiologic studies showed that an antioxidant supplementation decreases the state of oxidative stress. In the present work, a HFD-induced rat obesity and oxidative stress were used to investigate the link between fat deposition and serum-oxidative stress markers. We also studied the effect of a chronic administration of 3-keto-1,5-bisphosphonates 1 (a & b) (40 μg/kg/8 weeks/i.p.). Exposure of rats to HFD during 16 weeks induced fat deposition, weight gain and metabolic disruption characterized by an increase in cholesterol, triglyceride and glycemia levels, and a decrease in ionizable calcium and free iron concentrations. HFD also induced serum-oxidative stress status vocalized by an increase in ROS (H2 O2 ), MDA and PC levels, with a decrease in antioxidant enzyme activity (CAT, GPx, SOD). Importantly, 3-keto-1,5-bisphosphonates corrected all the deleterious effects of HFD treatment in vivo, but it failed to inhibit lipases in vitro and in vivo. These studies suggest that 3-keto-1,5-bisphosphonates 1 could be considered as safe antioxidant agents that should also find other potential biological applications. © 2014 John Wiley & Sons A/S.

  11. High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size.

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    Bourdier, Guillaume; Flore, Patrice; Sanchez, Hervé; Pepin, Jean-Louis; Belaidi, Elise; Arnaud, Claire

    2016-01-15

    Chronic intermittent hypoxia (IH) is described as the major detrimental factor leading to cardiovascular morbimortality in obstructive sleep apnea (OSA) patients. OSA patients exhibit increased infarct size after a myocardial event, and previous animal studies have shown that chronic IH could be the main mechanism. Endoplasmic reticulum (ER) stress plays a major role in the pathophysiology of cardiovascular disease. High-intensity training (HIT) exerts beneficial effects on the cardiovascular system. Thus, we hypothesized that HIT could prevent IH-induced ER stress and the increase in infarct size. Male Wistar rats were exposed to 21 days of IH (21-5% fraction of inspired O2, 60-s cycle, 8 h/day) or normoxia. After 1 wk of IH alone, rats were submitted daily to both IH and HIT (2 × 24 min, 15-30m/min). Rat hearts were either rapidly frozen to evaluate ER stress by Western blot analysis or submitted to an ischemia-reperfusion protocol ex vivo (30 min of global ischemia/120 min of reperfusion). IH induced cardiac proapoptotic ER stress, characterized by increased expression of glucose-regulated protein kinase 78, phosphorylated protein kinase-like ER kinase, activating transcription factor 4, and C/EBP homologous protein. IH-induced myocardial apoptosis was confirmed by increased expression of cleaved caspase-3. These IH-associated proapoptotic alterations were associated with a significant increase in infarct size (35.4 ± 3.2% vs. 22.7 ± 1.7% of ventricles in IH + sedenary and normoxia + sedentary groups, respectively, P < 0.05). HIT prevented both the IH-induced proapoptotic ER stress and increased myocardial infarct size (28.8 ± 3.9% and 21.0 ± 5.1% in IH + HIT and normoxia + HIT groups, respectively, P = 0.28). In conclusion, these findings suggest that HIT could represent a preventive strategy to limit IH-induced myocardial ischemia-reperfusion damages in OSA patients. Copyright © 2016 the American Physiological Society.

  12. Transdermal deferoxamine prevents pressure-induced diabetic ulcers

    Science.gov (United States)

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W.; Maan, Zeshaan N.; Rennert, Robert C.; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V.; Whitmore, Arnetha J.; Galvez, Michael G.; Whittam, Alexander J.; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C.

    2015-01-01

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation. PMID:25535360

  13. Taurine ameliorated homocysteine-induced H9C2 cardiomyocyte apoptosis by modulating endoplasmic reticulum stress.

    Science.gov (United States)

    Zhang, Zhimin; Zhao, Lianyou; Zhou, Yanfen; Lu, Xuanhao; Wang, Zhengqiang; Wang, Jipeng; Li, Wei

    2017-05-01

    Homocysteine (Hcy)-triggered endoplasmic reticulum (ER) stress-mediated endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury. However, whether ER stress is the molecular mechanism linking Hcy and cardiomyocytes death is unclear. Taurine has been reported to exert cardioprotective effects via various mechanisms. However, whether taurine protects against Hcy-induced cardiomyocyte death by attenuating ER stress is unknown. This study aimed to evaluate the opposite effects of taurine on Hcy-induced cardiomyocyte apoptosis and their underlying mechanisms. Our results demonstrated that low-dose or short-term Hcy treatment increased the expression of glucose-regulated protein 78 (GRP78) and activated protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6), which in turn prevented apoptotic cell death. High-dose Hcy or prolonged Hcy treatment duration significantly up-regulated levels of C/EBP homologous protein (CHOP), cleaved caspase-12, p-c-Jun N-terminal kinase (JNK), and then triggered apoptotic events. High-dose Hcy also resulted in a decrease in mitochondrial membrane potential (Δψm) and an increase in cytoplasmic cytochrome C and the expression of cleaved caspase-9. Pretreatment of cardiomyocytes with sodium 4-phenylbutyric acid (an ER stress inhibitor) significantly inhibited Hcy-induced apoptosis. Furthermore, blocking the PERK pathway partly alleviated Hcy-induced ER stress-modulated cardiomyocyte apoptosis, and down-regulated the levels of Bax and cleaved caspase-3. Experimental taurine pretreatment inhibited the expression of ER stress-related proteins, and protected against apoptotic events triggered by Hcy-induced ER stress. Taken together, our results suggest that Hcy triggered ER stress in cardiomyocytes, which was the crucial molecular mechanism mediating Hcy-induced cardiomyocyte apoptosis, and the adverse effect of Hcy could be prevented by taurine.

  14. Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

    Science.gov (United States)

    Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2017-01-01

    Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

  15. Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis

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    Lim Sung-Chul

    2011-09-01

    Full Text Available Abstract Background In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1, and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood. Results In the present study, we show that Distal-less 2 (Dlx-2, a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS in response to glucose deprivation (GD, one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an in vitro model of solid tumors. Dlx-2 short hairpin RNA (shRNA inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH release, indicating the important role(s of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis. Conclusions These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.

  16. α-Amyrin attenuates high fructose diet-induced metabolic syndrome in rats.

    Science.gov (United States)

    Prabhakar, Pankaj; Reeta, K H; Maulik, Subir Kumar; Dinda, Amit Kumar; Gupta, Yogendra Kumar

    2017-01-01

    This study investigated the effect of α-amyrin (a pentacyclic triterpene) on high-fructose diet (HFD)-induced metabolic syndrome in rats. Male Wistar rats were randomly distributed into different groups. The control group was fed normal rat chow diet. The HFD group was fed HFD (60%; w/w) for 42 days. Pioglitazone (10 mg/kg, orally, once daily) was used as a standard drug. α-Amyrin was administered in 3 doses (50, 100, and 200 mg/kg, orally, once daily along with HFD). Plasma glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were estimated. Changes in blood pressure, oral glucose tolerance, and insulin tolerance were measured. Hepatic oxidative stress as well as messenger RNA (mRNA) and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) were analyzed. A significant increase in systolic blood pressure, plasma glucose, total cholesterol, and plasma triglycerides and a significant decrease in HDL-C were observed in HFD rats as compared with control rats. Glucose tolerance and insulin tolerance were also significantly impaired with HFD. α-Amyrin prevented these changes in a dose-dependent manner. Hepatic oxidative stress as well as micro- and macrovesicular fatty changes in hepatocytes caused by HFD were also attenuated by α-amyrin. α-Amyrin preserved the hepatic mRNA and protein levels of PPAR-α, which was reduced in HFD group. This study thus demonstrates that α-amyrin attenuates HFD-induced metabolic syndrome in rats.

  17. Effects of Dietary Supplementation with Agaricus sylvaticus Schaeffer on Glycemia and Cholesterol after Streptozotocin-Induced Diabetes in Rats

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    Marcelo Betti Mascaro

    2014-01-01

    Full Text Available This study evaluated the effect of the Agaricus sylvaticus (sun mushroom on biochemical tests of the plasma and on the morphology of the pancreas in an experimental model of type I diabetes mellitus (DM1 induced by streptozotocin. One gram of dry A. sylvaticus was homogenized and mixed with the chow. Male Wistar rats were allocated as follows: normoglycemic control that received commercial chow; normoglycemic control group that received chow with A. sylvaticus; diabetic group that received commercial chow; and diabetic group that received chow with A. sylvaticus. Weight, food, and water consumption were measured every two days. Blood glucose levels were measured twice a week. After 30 days, the animals were euthanized and blood was collected for the analysis of cholesterol, HDL, triglycerides, blood sugar, glutamic-pyruvic transaminase (GPT, alkaline phosphatase, iron, transferrin, and urea. The pancreas was processed for microscopic analysis. A. sylvaticus modulated the levels of cholesterol, HDL, triglycerides, blood sugar, GPT, alkaline phosphatase, iron, transferrin, and urea to levels similar to those found in the controls and led to compensatory hyperplasia of the islets of Langerhans. A. sylvaticus is potentially beneficial in the control of type 1 diabetes, and it may also prevent pancreas damage.

  18. Role of Choline-Docosahexaenoic acid and Trigonella foenum graecum Seed Extract on Ovariectomy Induced Dyslipidemia and Oxidative Stress in Rat Model

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    Nagamma Takkella

    2018-01-01

    Full Text Available Background: Menopause is characterized by the deficiency of ovarian hormones, mainly estrogen. The decline in estrogen hormone is contributing the cardiovascular disorders in women. Hormone replacement therapy has disadvantages especially a higher risk of breast, ovarian and endometrial cancers upon chronic use. Phytoestrogens may be used as an alternative to hormone replacement therapy. Aim and Objectives: This study was designed to scientifically evaluate the role of Choline- Docosahexaenoic Acid (DHA and Trigonella foenum graecum (TFG seed extract on Ovariectomy (OVX induced dyslipidemia and oxidative stress in rat model. Material and Methods: Female Wistar rats were allocated into four groups (n=6:1 Sham control, 2 ovariectomized, 3 ovariectomized+ choline-DHA and 4 ovariectomized + choline-DHA+TFG. After 30 days of treatment, fasting blood samples and liver tissues were collected. Serum was analyzed for lipid profile and liver homogenates were used for assessment of oxidative stress and antioxidant activity. Results: Ovariectomized rats showed significantly increased (P<0.05 Total Cholesterol (TC, Low Density Lipoprotein (LDL levels and decreased High Density Lipoprotein (HDL levels. Treating ovariectomized rats with choline-DHA and TFG seed extract significantly lowered (P<0.05 total cholesterol, LDL and markedly increased the HDL. Significantly increased (P≤0.01 Thiobarbituric Acid Reactive Substances (TBARS and reduced (P<0.05 glutathione levels were observed in OVX group. The synergetic effect of choline-DHA and fenugreek showed a significant reduction ((P≤0.01 in TBARS levels. Conclusion: These results showed that choline-DHA with TFG supplementation have a favorable effect on OVX induced hyperlipidemia and oxidative stress. Therefore, these components may be a therapeutic agent for treating the menopause induced hyperlipidemia or oxidative stress.

  19. The Protective Role of Tempol Against Oxidative Stress-Related Renal Impairment Induced by Gamma Rays in Rats

    International Nuclear Information System (INIS)

    Mekawy, H.M.S.; Elkhouly, W.A.; Tawfik, S.S.

    2015-01-01

    Tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1 oxyl) is a naturally occurring substance that counteracts the harmful and damaging effects of oxidation in animal tissues and has been reported to permeate the biological membranes. In this study, tempol with dose of 18 mg/kg/day for 2 weeks has been shown to be effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage. Adult rats were exposed to a total dose of 6 Gy gamma rays to determine the protective role of tempol on the biochemistry of the injured kidney because gamma rays displayed significant augmentation in renal oxidative modifications markers.The results indicated that plasma renal function tests; urea (Ur), creatinine (Cr), uric acid (UA) and sodium (Na), and plasma renal tubular injury markers; γ -glutamyltransferase ( γ -GT), aspartate aminotransferase (AST), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), were increased significantly in gamma rays group. In addition, the renal oxidative stress parameters; malondialdehyde (MDA), total cholesterol (TC) and protein carbonyl (PC), were increased significantly, and reduced glutathione (GSH) was decreased significantly in gamma rays group. Moreover, the levels of renal antioxidant enzymes; superoxide dismutase (SOD) and catalase (CAT), were decreased significantly, and myeloperoxidase (MPO) was in creased significantly in gamma rays group.The antioxidant treatment with tempol ameliorates gamma rays-induced biochemical alterations and dysfunction of kidney.Tempol, at levels within tolerable nutritional strategy, reduced the oxidative modification-related renal impairment induced by gamma radiation in rats.

  20. Treating patients with low high-density lipoprotein cholesterol: choices, issues and opportunities

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    Watts Gerald F

    2001-05-01

    Full Text Available Abstract Three clinical trials have recently focused on the benefits of lipid-regulating therapy in populations with normocholesterolaemia and low high-density lipoprotein (HDL-cholesterol. Two secondary prevention studies (Veterans Affairs HDL-Cholesterol Intervention Trial [VA-HIT] and Bezafibrate Infarction Prevention [BIP] trial testified to the efficacy of fibrates in decreasing cardiovascular events, particularly in patients with coexisting risk factors, including hypertriglyceridaemia. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS demonstrated that a statin could decrease acute coronary events in patients with isolated low HDL-cholesterol in a primary prevention setting. The absolute risk reduction in coronary events in the VA-HIT study compares favourably with those reported from the statin-based Cholesterol and Recurrent Events (CARE and Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID trials. The absolute risk reduction in AFCAPS-TexCAPS is similar to that in West of Scotland Coronary Pravastatin Study (WOSCOPS. Recommendations are given concerning lifestyle and pharmacological management of low HDL-cholesterol. Optimal management also requires review of current treatment targets for HDL-cholesterol and triglycerides levels.

  1. Down-regulation of lipid raft-associated onco-proteins via cholesterol-dependent lipid raft internalization in docosahexaenoic acid-induced apoptosis.

    Science.gov (United States)

    Lee, Eun Jeong; Yun, Un-Jung; Koo, Kyung Hee; Sung, Jee Young; Shim, Jaegal; Ye, Sang-Kyu; Hong, Kyeong-Man; Kim, Yong-Nyun

    2014-01-01

    Lipid rafts, plasma membrane microdomains, are important for cell survival signaling and cholesterol is a critical lipid component for lipid raft integrity and function. DHA is known to have poor affinity for cholesterol and it influences lipid rafts. Here, we investigated a mechanism underlying the anti-cancer effects of DHA using a human breast cancer cell line, MDA-MB-231. We found that DHA decreased cell surface levels of lipid rafts via their internalization, which was partially reversed by cholesterol addition. With DHA treatment, caveolin-1, a marker for rafts, and EGFR were colocalized with LAMP-1, a lysosomal marker, in a cholesterol-dependent manner, indicating that DHA induces raft fusion with lysosomes. DHA not only displaced several raft-associated onco-proteins, including EGFR, Hsp90, Akt, and Src, from the rafts but also decreased total levels of those proteins via multiple pathways, including the proteasomal and lysosomal pathways, thereby decreasing their activities. Hsp90 overexpression maintained its client proteins, EGFR and Akt, and attenuated DHA-induced cell death. In addition, overexpression of Akt or constitutively active Akt attenuated DHA-induced apoptosis. All these data indicate that the anti-proliferative effect of DHA is mediated by targeting of lipid rafts via decreasing cell surface lipid rafts by their internalization, thereby decreasing raft-associated onco-proteins via proteasomal and lysosomal pathways and decreasing Hsp90 chaperone function. © 2013.

  2. Hydroxyurea-Induced Replication Stress

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    Kenza Lahkim Bennani-Belhaj

    2010-01-01

    Full Text Available Bloom's syndrome (BS displays one of the strongest known correlations between chromosomal instability and a high risk of cancer at an early age. BS cells combine a reduced average fork velocity with constitutive endogenous replication stress. However, the response of BS cells to replication stress induced by hydroxyurea (HU, which strongly slows the progression of replication forks, remains unclear due to publication of conflicting results. Using two different cellular models of BS, we showed that BLM deficiency is not associated with sensitivity to HU, in terms of clonogenic survival, DSB generation, and SCE induction. We suggest that surviving BLM-deficient cells are selected on the basis of their ability to deal with an endogenous replication stress induced by replication fork slowing, resulting in insensitivity to HU-induced replication stress.

  3. Differential Membrane Dipolar Orientation Induced by Acute and Chronic Cholesterol Depletion.

    Science.gov (United States)

    Sarkar, Parijat; Chakraborty, Hirak; Chattopadhyay, Amitabha

    2017-06-30

    Cholesterol plays a crucial role in cell membrane organization, dynamics and function. Depletion of cholesterol represents a popular approach to explore cholesterol-sensitivity of membrane proteins. An emerging body of literature shows that the consequence of membrane cholesterol depletion often depends on the actual process (acute or chronic), although the molecular mechanism underlying the difference is not clear. Acute depletion, using cyclodextrin-type carriers, is faster relative to chronic depletion, in which inhibitors of cholesterol biosynthesis are used. With the overall goal of addressing molecular differences underlying these processes, we monitored membrane dipole potential under conditions of acute and chronic cholesterol depletion in CHO-K1 cells, using a voltage-sensitive fluorescent dye in dual wavelength ratiometric mode. Our results show that the observed membrane dipole potential exhibits difference under acute and chronic cholesterol depletion conditions, even when cholesterol content was identical. To the best of our knowledge, these results provide, for the first time, molecular insight highlighting differences in dipolar reorganization in these processes. A comprehensive understanding of processes in which membrane cholesterol gets modulated would provide novel insight in its interaction with membrane proteins and receptors, thereby allowing us to understand the role of cholesterol in cellular physiology associated with health and disease.

  4. Supplementation with fish oil and coconut fat prevents prenatal stress-induced changes in early postnatal development.

    Science.gov (United States)

    Borsonelo, Elizabethe C; Suchecki, Deborah; Calil, Helena Maria; Galduróz, José Carlos F

    2011-08-01

    Adequate development of the central nervous system depends on prenatal and postnatal factors. On one hand, prenatal stress (PNS) has been implicated in impaired development of the offspring. On other hand, nutritional factors during pregnancy and lactation can influence fetal and postnatal growth. This study assessed the postnatal development of rat offspring exposed to PNS, which consisted of restraint and bright lights, 3 times/day, from days 14 to 20 of pregnancy, whose mothers were fed different diets during pregnancy and lactation: regular diet, diet supplemented with coconut fat or fish oil. When pregnancy was confirmed, they were distributed into control (CTL) or PNS groups. At birth, PNS males and females weighed less than those in the group CTL. At 21 days of age, this alteration was no longer observed with fish oil and coconut fat groups. PNS and coconut fat diet induced increased locomotor activity in 13 day old male and female pups, and this effect was prevented by fish oil supplementation only in females. In conclusion, postnatal development from birth to weaning was influenced by PNS and diet and some of those alterations were prevented by coconut fat and fish oil. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  5. Ameliorating role of rutin on oxidative stress induced by iron overload in hepatic tissue of rats.

    Science.gov (United States)

    Aziza, Samy Ali Hussein; Azab, Mohammed El-Said; El-Shall, Soheir Kamal

    2014-08-01

    Iron is an essential element that participates in several metabolic activities of cells; however, excess iron is a major cause of iron-induced oxidative stress and several human diseases. Natural flavonoids, as rutin, are well-known antioxidants and could be efficient protective agents. Therefore, the present study was undertaken to evaluate the protective influence of rutin supplementation to improve rat antioxidant systems against IOL-induced hepatic oxidative stress. Sixty male albino rats were randomly divided to three equal groups. The first group, the control, the second group, iron overload group, the third group was used as iron overload+rutin group. Rats received six doses of ferric hydroxide polymaltose (100 mg kg(-1) b.wt.) as one dose every two days, by intraperitoneal injections (IP) and administrated rutin (50 mg kg(-1) b.wt.) as one daily oral dose until the sacrificed day. Blood samples for serum separation and liver tissue specimens were collected three times, after three, four and five weeks from the onset of the experiment. Serum iron profiles total iron, Total Iron Binding Capacity (TIBC), Unsaturated Iron Binding Capacity (UIBC), transferrin (Tf) and Transferrin Saturation% (TS%)}, ferritin, albumin, total Protein, total cholesterol, triacylglycerols levels and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were determined. Moreover, total iron in the liver, L-malondialdehyde (L-MDA), glutathione (GSH), Nitric Oxide (NO) and Total Nucleic Acid (TNA) levels and glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activities were also determined. The obtained results revealed that, iron overload (IOL) resulted in significant increase in serum iron, TIBC, Tf, TS% and ferritin levels and AST and ALT activities and also increased liver iron, L-MDA and NO levels. Meanwhile, it decreased serum UIBC, total cholesterol, triacylglycerols, albumin, total protein and liver GSH, TNA levels and Gpx, CAT

  6. Cholesterol autoxidation in phospholipid membrane bilayers

    International Nuclear Information System (INIS)

    Sevanian, A.; McLeod, L.L.

    1987-01-01

    Lipid peroxidation in unilamellar liposomes of known cholesterol-phospholipid composition was monitored under conditions of autoxidation or as induced by a superoxide radical generating system, gamma-irradiation or cumene hydroperoxide. Formation of cholesterol oxidation products was indexed to the level of lipid peroxidation. The major cholesterol oxidation products identified were 7-keto-cholesterol, isomeric cholesterol 5,6-epoxides, isomeric 7-hydroperoxides and isomeric 3,7-cholestane diols. Other commonly encountered products included 3,5-cholestadiene-7-one and cholestane-3 beta, 5 alpha, 6 beta-triol. Superoxide-dependent peroxidation required iron and produced a gradual increase in 7-keto-cholesterol and cholesterol epoxides. Cholesterol oxidation was greatest in liposomes containing high proportions of unsaturated phospholipid to cholesterol (4:1 molar ratio), intermediate with low phospholipid to cholesterol ratios (2:1) and least in liposomes prepared with dipalmitoylphosphatidylcholine and cholesterol. This relationship held regardless of the oxidizing conditions used. Cumene hydroperoxide-dependent lipid peroxidation and/or more prolonged oxidations with other oxidizing systems yielded a variety of products where cholesterol-5 beta,6 beta-epoxide, 7-ketocholesterol and the 7-hydroperoxides were most consistently elevated. Oxyradical initiation of lipid peroxidation produced a pattern of cholesterol oxidation products distinguishable from the pattern derived by cumene hydroperoxide-dependent peroxidation

  7. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-κB, p38 and JNK MAPK pathway

    International Nuclear Information System (INIS)

    Ghosh, Jyotirmoy; Das, Joydeep; Manna, Prasenjit; Sil, Parames C.

    2009-01-01

    Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-κB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-κB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-κB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-κB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As-induced

  8. Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis.

    Science.gov (United States)

    Das, S; Ray, R; Snehlata; Das, N; Srivastava, L M

    2006-04-01

    The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

  9. Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity.

    Science.gov (United States)

    Chen, Yaqin; Wu, Zhihong; Zhao, Shuiping; Xiang, Rong

    2016-06-08

    Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese.

  10. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    OpenAIRE

    Matthias Orth; Stefano Bellosta

    2012-01-01

    Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein...

  11. Heat Stress-Induced PI3K/mTORC2-Dependent AKT Signaling Is a Central Mediator of Hepatocellular Carcinoma Survival to Thermal Ablation Induced Heat Stress.

    Directory of Open Access Journals (Sweden)

    Scott M Thompson

    Full Text Available Thermal ablative therapies are important treatment options in the multidisciplinary care of patients with hepatocellular carcinoma (HCC, but lesions larger than 2-3 cm are plagued with high local recurrence rates and overall survival of these patients remains poor. Currently no adjuvant therapies exist to prevent local HCC recurrence in patients undergoing thermal ablation. The molecular mechanisms mediating HCC resistance to thermal ablation induced heat stress and local recurrence remain unclear. Here we demonstrate that the HCC cells with a poor prognostic hepatic stem cell subtype (Subtype HS are more resistant to heat stress than HCC cells with a better prognostic hepatocyte subtype (Subtype HC. Moreover, sublethal heat stress rapidly induces phosphoinositide 3-kinase (PI3K/mammalian target of rapamycin (mTOR dependent-protein kinase B (AKT survival signaling in HCC cells in vitro and at the tumor ablation margin in vivo. Conversely, inhibition of PI3K/mTOR complex 2 (mTORC2-dependent AKT phosphorylation or direct inhibition of AKT function both enhance HCC cell killing and decrease HCC cell survival to sublethal heat stress in both poor and better prognostic HCC subtypes while mTOR complex 1 (mTORC1-inhibition has no impact. Finally, we showed that AKT isoforms 1, 2 and 3 are differentially upregulated in primary human HCCs and that overexpression of AKT correlates with worse tumor biology and pathologic features (AKT3 and prognosis (AKT1. Together these findings define a novel molecular mechanism whereby heat stress induces PI3K/mTORC2-dependent AKT survival signaling in HCC cells and provide a mechanistic rationale for adjuvant AKT inhibition in combination with thermal ablation as a strategy to enhance HCC cell killing and prevent local recurrence, particularly at the ablation margin.

  12. Effect of taurine supplementation on hyperhomocysteinemia and markers of oxidative stress in high fructose diet induced insulin resistance

    Directory of Open Access Journals (Sweden)

    El Mesallamy Hala O

    2010-06-01

    Full Text Available Abstract Background High intake of dietary fructose is accused of being responsible for the development of the insulin resistance (IR syndrome. Concern has arisen because of the realization that fructose, at elevated concentrations, can promote metabolic changes that are potentially deleterious. Among these changes is IR which manifests as a decreased biological response to normal levels of plasma insulin. Methods Oral glucose tolerance tests (OGTT were carried out, homeostasis model assessment of insulin resistance (HOMA was calculated, homocysteine (Hcy, lipid concentrations and markers of oxidative stress were measured in male Wistar rats weighing 170-190 g. The rats were divided into four groups, kept on either control diet or high fructose diet (HFD, and simultaneously supplemented with 300 mg/kg/day taurine via intra-peritoneal (i.p. route for 35 days. Results Fructose-fed rats showed significantly impaired glucose tolerance, impaired insulin sensitivity, hypertriglyceridemia, hypercholesterolemia, hyperhomocysteinemia (HHcy, lower total antioxidant capacity (TAC, lower paraoxonase (PON activity, and higher nitric oxide metabolites (NOx concentration, when compared to rats fed on control diet. Supplementing the fructose-fed rats with taurine has ameliorated the rise in HOMA by 56%, triglycerides (TGs by 22.5%, total cholesterol (T-Chol by 11%, and low density lipoprotein cholesterol (LDL-C by 21.4%. Taurine also abolished any significant difference of TAC, PON activity and NOx concentration among treated and control groups. TAC positively correlated with PON in both rats fed on the HFD and those received taurine in addition to the HFD. Fructose-fed rats showed 34.7% increase in Hcy level. Taurine administration failed to prevent the observed HHcy in the current dosage and duration. Conclusion Our results indicate that HFD could induce IR which could further result in metabolic syndrome (MS, and that taurine has a protective role against

  13. Dopamine D1 receptors are responsible for stress-induced emotional memory deficit in mice.

    Science.gov (United States)

    Wang, Yongfu; Wu, Jing; Zhu, Bi; Li, Chaocui; Cai, Jing-Xia

    2012-03-01

    It is established that stress impairs spatial learning and memory via the hypothalamus-pituitary-adrenal axis response. Dopamine D1 receptors were also shown to be responsible for a stress-induced deficit of working memory. However, whether stress affects the subsequent emotional learning and memory is not elucidated yet. Here, we employed the well-established one-trial step-through task to study the effect of an acute psychological stress (induced by tail hanging for 5, 10, or 20 min) on emotional learning and memory, and the possible mechanisms as well. We demonstrated that tail hanging induced an obvious stress response. Either an acute tail-hanging stress or a single dose of intraperitoneally injected dopamine D1 receptor antagonist (SCH23390) significantly decreased the step-through latency in the one-trial step-through task. However, SCH23390 prevented the acute tail-hanging stress-induced decrease in the step-through latency. In addition, the effects of tail-hanging stress and/or SCH23390 on the changes in step-through latency were not through non-memory factors such as nociceptive perception and motor function. Our data indicate that the hyperactivation of dopamine D1 receptors mediated the stress-induced deficit of emotional learning and memory. This study may have clinical significance given that psychological stress is considered to play a role in susceptibility to some mental diseases such as depression and post-traumatic stress disorder.

  14. Protective effect of lemongrass oil against dexamethasone induced hyperlipidemia in rats: possible role of decreased lecithin cholesterol acetyl transferase activity.

    Science.gov (United States)

    Kumar, V R Santhosh; Inamdar, Md Naseeruddin; Nayeemunnisa; Viswanatha, G L

    2011-08-01

    To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats. Administration of dexamethasone was given at 10 mg/kg, sc. to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index. Lemongrass oil (100 and 200 mg/kg, po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg, po. The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase (LCAT) activity. These results suggested that Lemon gross oil possess significant anti-hyperlipidemic activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  15. Stress-induced hyperthermia in translational stress research

    NARCIS (Netherlands)

    Vinkers, C.H.; Penning, R.; Ebbens, M.M.; Helhammer, J.; Verster, J.C.; Kalkman, C.J.; Olivier, B.

    2010-01-01

    The stress-induced hyperthermia (SIH) response is the transient change in body temperature in response to acute stress. This body temperature response is part of the autonomic stress response which also results in tachycardia and an increased blood pressure. So far, a SIH response has been found in

  16. Inhibition of protein kinase C affects on mode of synaptic vesicle exocytosis due to cholesterol depletion

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, Alexey M., E-mail: fysio@rambler.ru; Zakyrjanova, Guzalija F., E-mail: guzik121192@mail.ru; Yakovleva, Anastasia A., E-mail: nastya1234qwer@mail.ru; Zefirov, Andrei L., E-mail: zefiroval@rambler.ru

    2015-01-02

    Highlights: • We examine the involvement of PKC in MCD induced synaptic vesicle exocytosis. • PKC inhibitor does not decrease the effect MCD on MEPP frequency. • PKC inhibitor prevents MCD induced FM1-43 unloading. • PKC activation may switch MCD induced exocytosis from kiss-and-run to a full mode. • Inhibition of phospholipase C does not lead to similar change in exocytosis. - Abstract: Previous studies demonstrated that depletion of membrane cholesterol by 10 mM methyl-beta-cyclodextrin (MCD) results in increased spontaneous exocytosis at both peripheral and central synapses. Here, we investigated the role of protein kinase C in the enhancement of spontaneous exocytosis at frog motor nerve terminals after cholesterol depletion using electrophysiological and optical methods. Inhibition of the protein kinase C by myristoylated peptide and chelerythrine chloride prevented MCD-induced increases in FM1-43 unloading, whereas the frequency of spontaneous postsynaptic events remained enhanced. The increase in FM1-43 unloading still could be observed if sulforhodamine 101 (the water soluble FM1-43 quencher that can pass through the fusion pore) was added to the extracellular solution. This suggests a possibility that exocytosis of synaptic vesicles under these conditions could occur through the kiss-and-run mechanism with the formation of a transient fusion pore. Inhibition of phospholipase C did not lead to similar change in MCD-induced exocytosis.

  17. Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic.

    Science.gov (United States)

    Ortega-Domínguez, Bibiana; Aparicio-Trejo, Omar Emiliano; García-Arroyo, Fernando E; León-Contreras, Juan Carlos; Tapia, Edilia; Molina-Jijón, Eduardo; Hernández-Pando, Rogelio; Sánchez-Lozada, Laura Gabriela; Barrera-Oviedo, Diana; Pedraza-Chaverri, José

    2017-09-01

    Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model. It was found that curcumin prevents cisplatin-induced: (a) AKI and (b) alterations in the following mitochondrial parameters: bioenergetics, ultrastructure, hydrogen peroxide production and dynamic. In fact, curcumin prevented the increase of mitochondrial fission 1 protein (FIS1), the decrease of optic atrophy 1 protein (OPA1) and the decrease of NAD + -dependent deacetylase sirtuin-3 (SIRT3), a mitochondrial dynamic regulator as well as the increase in the mitophagy associated proteins parkin and phosphatase and tensin homologue (PTEN)-induced putative kinase protein 1 (PINK1). In conclusion, the protective effect of curcumin in cisplatin-induced AKI was associated with the prevention of the alterations in mitochondrial bioenergetics, ultrastructure, redox balance, dynamic, and SIRT3 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. New Horizons in Organizational Stress Prevention Approaches.

    Science.gov (United States)

    McGaffey, Thomas N.

    1978-01-01

    Discusses and describes some active Employee Assistance Programs (EAPs). An EAP is a stress intervention program that, when combined with other stress prevention procedures, can serve as an effective base for developing a comprehensive managerial system for combating organizational stress. (Author/IRT)

  19. Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism: implications for breast cancer prevention.

    Science.gov (United States)

    Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Lamb, Rebecca; Hulit, James; Howell, Anthony; Sotgia, Federica; Rubin, Emanuel; Lisanti, Michael P

    2013-01-15

    Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with "stemness," more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This "two-compartment" metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert "low-risk" breast cancer patients to "high-risk" status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results also show that

  20. Long-term vegetarians have low oxidative stress, body fat, and cholesterol levels.

    Science.gov (United States)

    Kim, Mi Kyung; Cho, Sang Woon; Park, Yoo Kyoung

    2012-04-01

    Excessive oxidative stress and abnormal blood lipids may cause chronic diseases. This risk can be reduced by consuming an antioxidant- and fiber-rich vegetarian diet. We compared biomarkers of oxidative stress, antioxidant capacity, and lipid profiles of sex- and age-matched long-term vegetarians and omnivores in Korea. Forty-five vegetarians (23 men and 22 women; mean age, 49.5 ± 5.3 years), who had maintained a vegetarian diet for a minimum of 15 years, and 30 omnivores (15 men and 15 women; mean age, 48.9 ± 3.6 years) participated in this study. Their 1-day, 24-h recall, and 2-day dietary records were analyzed. Oxidative stress was measured by the levels of diacron reactive oxygen metabolites (d-ROM). Antioxidant status was determined by the biological antioxidant potential (BAP) and levels of endogenous antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. We observed that vegetarians had a significantly lower body fat percentage (21.6 ± 6.4%) than that of omnivores (25.4 ± 4.6%; P vegetarians than those in omnivores (331.82 ± 77.96 and 375.80 ± 67.26 Carratelli units; P vegetarians and omnivores were 173.73 ± 31.42 mg/dL and 193.17 ± 37.89 mg/dL, respectively (P vegetarians and omnivores, respectively, indicating that vegetarians had significantly lower lipid levels. Thus, oxidative stress, body fat, and cholesterol levels were lower in long-term vegetarians than those in omnivores.

  1. Cold stress induces lower urinary tract symptoms.

    Science.gov (United States)

    Imamura, Tetsuya; Ishizuka, Osamu; Nishizawa, Osamu

    2013-07-01

    Cold stress as a result of whole-body cooling at low environmental temperatures exacerbates lower urinary tract symptoms, such as urinary urgency, nocturia and residual urine. We established a model system using healthy conscious rats to explore the mechanisms of cold stress-induced detrusor overactivity. In this review, we summarize the basic findings shown by this model. Rats that were quickly transferred from room temperature (27 ± 2°C) to low temperature (4 ± 2°C) showed detrusor overactivity including increased basal pressure and decreased voiding interval, micturition volume, and bladder capacity. The cold stress-induced detrusor overactivity is mediated through a resiniferatoxin-sensitve C-fiber sensory nerve pathway involving α1-adrenergic receptors. Transient receptor potential melastatin 8 channels, which are sensitive to thermal changes below 25-28°C, also play an important role in mediating the cold stress responses. Additionally, the sympathetic nervous system is associated with transient hypertension and decreases of skin surface temperature that are closely correlated with the detrusor overactivity. With this cold stress model, we showed that α1-adrenergic receptor antagonists have the potential to treat cold stress-exacerbated lower urinary tract symptoms. In addition, we showed that traditional Japanese herbal mixtures composed of Hachimijiogan act, in part, by increasing skin temperature and reducing the number of cold sensitive transient receptor potential melastatin channels in the skin. The effects of herbal mixtures have the potential to treat and/or prevent the exacerbation of lower urinary tract symptoms by providing resistance to the cold stress responses. Our model provides new opportunities for utilizing animal disease models with altered lower urinary tract functions to explore the effects of novel therapeutic drugs. © 2013 The Japanese Urological Association.

  2. Toxic Stress: Effects, Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Hillary A. Franke

    2014-11-01

    Full Text Available Children who experience early life toxic stress are at risk of long-term adverse health effects that may not manifest until adulthood. This article briefly summarizes the findings in recent studies on toxic stress and childhood adversity following the publication of the American Academy of Pediatrics (AAP Policy Report on the effects of toxic stress. A review of toxic stress and its effects is described, including factors of vulnerability, resilience, and the relaxation response. An integrative approach to the prevention and treatment of toxic stress necessitates individual, community and national focus.

  3. Tips for Disaster Responders: Preventing and Managing Stress

    Science.gov (United States)

    ... actions to prevent stress and to strengthen your stress management skills is before your disaster assignment. Responder stress ... the disaster role, developing a personal toolkit of stress management skills, and preparing yourself and your loved ones. ...

  4. The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

    Science.gov (United States)

    Shor, Erika; Fox, Catherine A.; Broach, James R.

    2013-01-01

    Conditions of chronic stress are associated with genetic instability in many organisms, but the roles of stress responses in mutagenesis have so far been elucidated only in bacteria. Here, we present data demonstrating that the environmental stress response (ESR) in yeast functions in mutagenesis induced by proteotoxic stress. We show that the drug canavanine causes proteotoxic stress, activates the ESR, and induces mutagenesis at several loci in an ESR-dependent manner. Canavanine-induced mutagenesis also involves translesion DNA polymerases Rev1 and Polζ and non-homologous end joining factor Ku. Furthermore, under conditions of chronic sub-lethal canavanine stress, deletions of Rev1, Polζ, and Ku-encoding genes exhibit genetic interactions with ESR mutants indicative of ESR regulating these mutagenic DNA repair processes. Analyses of mutagenesis induced by several different stresses showed that the ESR specifically modulates mutagenesis induced by proteotoxic stress. Together, these results document the first known example of an involvement of a eukaryotic stress response pathway in mutagenesis and have important implications for mechanisms of evolution, carcinogenesis, and emergence of drug-resistant pathogens and chemotherapy-resistant tumors. PMID:23935537

  5. Chloride secretion induced by rotavirus is oxidative stress-dependent and inhibited by Saccharomyces boulardii in human enterocytes.

    Science.gov (United States)

    Buccigrossi, Vittoria; Laudiero, Gabriella; Russo, Carla; Miele, Erasmo; Sofia, Morena; Monini, Marina; Ruggeri, Franco Maria; Guarino, Alfredo

    2014-01-01

    Rotavirus (RV) infection causes watery diarrhea via multiple mechanisms, primarily chloride secretion in intestinal epithelial cell. The chloride secretion largely depends on non-structural protein 4 (NSP4) enterotoxic activity in human enterocytes through mechanisms that have not been defined. Redox imbalance is a common event in cells infected by viruses, but the role of oxidative stress in RV infection is unknown. RV SA11 induced chloride secretion in association with an increase in reactive oxygen species (ROS) in Caco-2 cells. The ratio between reduced (GSH) and oxidized (GSSG) glutathione was decreased by RV. The same effects were observed when purified NSP4 was added to Caco-2 cells. N-acetylcysteine (NAC), a potent antioxidant, strongly inhibited the increase in ROS and GSH imbalance. These results suggest a link between oxidative stress and RV-induced diarrhea. Because Saccharomyces boulardii (Sb) has been effectively used to treat RV diarrhea, we tested its effects on RV-infected cells. Sb supernatant prevented RV-induced oxidative stress and strongly inhibited chloride secretion in Caco-2 cells. These results were confirmed in an organ culture model using human intestinal biopsies, demonstrating that chloride secretion induced by RV-NSP4 is oxidative stress-dependent and is inhibited by Sb, which produces soluble metabolites that prevent oxidative stress. The results of this study provide novel insights into RV-induced diarrhea and the efficacy of probiotics.

  6. Increased hepatic cholesterol esterification with essential fatty acid deficiency (EFAD): relationship to plasma lipoprotein (LP) cholesterol content

    International Nuclear Information System (INIS)

    Ney, D.M.; Ziboh, V.A.; Schneeman, B.O.

    1986-01-01

    EFAD in the rat is associated with hepatic accumulation of esterified cholesterol and altered distribution of cholesterol between plasma and hepatic tissue. Little is known regarding the impact of EFAD on LP composition. To determine the relationship between hepatic cholesterol esterification and plasma lP composition in control (C) and EFAD male Wistar rats, the authors induced EFAD with continuous intragastric (IG) infusion of EFA-free solutions containing 3.5% of calories as triolein for 7 and 14 days. C animals received IG infusion of solutions containing 3.5% of calories as linoleic acid. Data in the EFAD groups reveal: (i) marked decreases in hepatic EFAs and increases in monoenoic acids; (ii) progressive increases in hepatic content of triglyceride and esterified cholesterol with 7 and 14 days of feeding; (iii) assay of acyl CoA:cholesterol acyltransferase activity in hepatic tissue using 14 C-cholesterol demonstrates an increase in hepatic cholesterol esterification when compared to C animals. Increased hepatic cholesterol esterification correlates with elevated levels of esterified cholesterol in plasma VLDL and HDL particles. These data indicate that the elevated levels of cholesterol esters in LP particles is due, at least in part, to increased hepatic cholesterol esterification with EFAD

  7. Taurocholate Deconjugation and Cholesterol Binding by Indigenous Dadih Lactic Acid Bacteria

    Directory of Open Access Journals (Sweden)

    USMAN PATO

    2005-09-01

    Full Text Available High serum cholesterol levels have been associated with an increased risk for human coronary heart disease. Lowering of serum cholesterol has been suggested to prevent the heart disease. To reduce serum cholesterol levels one may consumed diet supplementat of fermented dairy product such as dadih. Lactic acid bacteria present in dadih may alter serum cholesterol by directly bind to dietary cholesterol and/or deconjugation of bile salts. Acid and bile tolerance, deconjugation of sodium taurocholate, and the cholesterol-binding ability of lactic acid bacteria from dadih were examined. Among ten dadih lactic acid bacteria tested, six strains namely I-11, I-2775, K-5, I-6257, IS-7257, and B-4 could bind cholesterol and deconjugate sodium taurocholate. However, the last four strains were very sensitive to bile. Therefore, Lactobacillus fermentum I-11 and Leuconostoc lactis subsp. lactis I-2775 those were tolerant to acid and oxgall (bile and deconjugated sodium taurocholate and bound cholesterol could be recommended as probiotic to prevent coronary heart disease.

  8. Cholesterol Check (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    Heart disease and stroke are among the leading causes of death in the U.S. One of the main risk factors is high blood cholesterol. In this podcast, Dr. Carla Mercado discusses the importance of a healthy diet and regular screening to prevent high blood cholesterol.

  9. Model approach for stress induced steroidal hormone cascade changes in severe mental diseases.

    Science.gov (United States)

    Volko, Claus D; Regidor, Pedro A; Rohr, Uwe D

    2016-03-01

    Stress was described by Cushing and Selye as an adaptation to a foreign stressor by the anterior pituitary increasing ACTH, which stimulates the release of glucocorticoid and mineralocorticoid hormones. The question is raised whether stress can induce additional steroidal hormone cascade changes in severe mental diseases (SMD), since stress is the common denominator. A systematic literature review was conducted in PubMed, where the steroidal hormone cascade of patients with SMD was compared to the impact of increasing stress on the steroidal hormone cascade (a) in healthy amateur marathon runners with no overtraining; (b) in healthy well-trained elite soldiers of a ranger training unit in North Norway, who were under extreme physical and mental stress, sleep deprivation, and insufficient calories for 1 week; and, (c) in soldiers suffering from post traumatic stress disorder (PTSD), schizophrenia (SI), and bipolar disorders (BD). (a) When physical stress is exposed moderately to healthy men and women for 3-5 days, as in the case of amateur marathon runners, only few steroidal hormones are altered. A mild reduction in testosterone, cholesterol and triglycerides is detected in blood and in saliva, but there was no decrease in estradiol. Conversely, there is an increase of the glucocorticoids, aldosterone and cortisol. Cellular immunity, but not specific immunity, is reduced for a short time in these subjects. (b) These changes are also seen in healthy elite soldiers exposed to extreme physical and mental stress but to a somewhat greater extent. For instance, the aldosterone is increased by a factor of three. (c) In SMD, an irreversible effect on the entire steroidal hormone cascade is detected. Hormones at the top of the cascade, such as cholesterol, dehydroepiandrosterone (DHEA), aldosterone and other glucocorticoids, are increased. However, testosterone and estradiol and their metabolites, and other hormones at the lower end of the cascade, seem to be reduced. 1

  10. The Effects of Silymarin on Oxidative Status and Bone Characteristics in Japanese Quail Subjected to Oxidative Stress Induced by Carbon Tetrachloride

    Directory of Open Access Journals (Sweden)

    Moradi F

    2017-10-01

    Full Text Available This experiment was conducted to assess the effects of Silymarin on oxidative status, bone characteristics, and some blood parameters in Japanese quail subjected to oxidative stress induced by carbon tetrachloride (CCl4. The experiment was performed as a completely randomized design with four replicates, each with 30 birds, using a 2 × 2 factorial arrangement with two doses of Silymarin (0 and 1 mL/kg BW and CCl4 (0 and 1 mL/kg BW. Results revealed that the interaction between Silymarin and CCl4on concentrations of total cholesterol, triglycerides, glucose, albumin, calcium, and alkaline phosphatase were significant (P < 0.05. In contrast, concentrations of phosphorus, total protein, and high density lipoprotein-cholesterol in blood serum did not differ between experimental treatments. Experimental treatments had a significant effect on superoxide dismutase activity in blood serum (P < 0.05, but not on glutathione peroxide activity and malondialdehyde concentration. Experimental treatments significantly affected the weight, thickness, and external and internal diameters of tibia bone (P < 0.05, but not its length, ash, volume, and density. This study shows that Silymarin has potential to attenuate adverse effects of oxidative stress induced by CCl4 in Japanese quail.

  11. Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xin; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China 201203 (China); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China 201203 (China)

    2017-04-01

    Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD-induced

  12. Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells

    International Nuclear Information System (INIS)

    Wang, Xin; Xu, Mei; Frank, Jacqueline A.; Ke, Zun-ji; Luo, Jia

    2017-01-01

    Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD-induced

  13. Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.

    Science.gov (United States)

    Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans

    2018-03-01

    Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. What Can We Learn about Cholesterol's Transmembrane Distribution Based on Cholesterol-Induced Changes in Membrane Dipole Potential?

    DEFF Research Database (Denmark)

    Falkovich, Stanislav G.; Martinez-Seara, Hector; Nesterenko, Alexey M.

    2016-01-01

    Cholesterol is abundant in the plasma membranes of animal cells and is known to regulate a variety of membrane properties. Despite decades of research, the transmembrane distribution of cholesterol is still a matter of debate. Here we consider this outstanding issue through atomistic simulations ...

  15. Basolateral amygdala GABA-A receptors mediate stress-induced memory retrieval impairment in rats.

    Science.gov (United States)

    Sardari, Maryam; Rezayof, Ameneh; Khodagholi, Fariba; Zarrindast, Mohammad-Reza

    2014-04-01

    The present study was designed to investigate the involvement of GABA-A receptors of the basolateral amygdala (BLA) in the impairing effect of acute stress on memory retrieval. The BLAs of adult male Wistar rats were bilaterally cannulated and memory retrieval was measured in a step-through type passive avoidance apparatus. Acute stress was evoked by placing the animals on an elevated platform for 10, 20 and 30 min. The results indicated that exposure to 20 and 30 min stress, but not 10 min, before memory retrieval testing (pre-test exposure to stress) decreased the step-through latency, indicating stress-induced memory retrieval impairment. Intra-BLA microinjection of a GABA-A receptor agonist, muscimol (0.005-0.02 μg/rat), 5 min before exposure to an ineffective stress (10 min exposure to stress) induced memory retrieval impairment. It is important to note that pre-test intra-BLA microinjection of the same doses of muscimol had no effect on memory retrieval in the rats unexposed to 10 min stress. The blockade of GABA-A receptors of the BLA by injecting an antagonist, bicuculline (0.4-0.5 μg/rat), 5 min before 20 min exposure to stress, prevented stress-induced memory retrieval. Pre-test intra-BLA microinjection of the same doses of bicuculline (0.4-0.5 μg/rat) in rats unexposed to 20 min stress had no effect on memory retrieval. In addition, pre-treatment with bicuculline (0.1-0.4 μg/rat, intra-BLA) reversed muscimol (0.02 μg/rat, intra-BLA)-induced potentiation on the effect of stress in passive avoidance learning. It can be concluded that pre-test exposure to stress can induce memory retrieval impairment and the BLA GABA-A receptors may be involved in stress-induced memory retrieval impairment.

  16. Stress induced reorientation of vanadium hydride

    International Nuclear Information System (INIS)

    Beardsley, M.B.

    1977-10-01

    The critical stress for the reorientation of vanadium hydride was determined for the temperature range 180 0 to 280 0 K using flat tensile samples containing 50 to 500 ppM hydrogen by weight. The critical stress was observed to vary from a half to a third of the macroscopic yield stress of pure vanadium over the temperature range. The vanadium hydride could not be stress induced to precipitate above its stress-free precipitation temperature by uniaxial tensile stresses or triaxial tensile stresses induced by a notch

  17. Preventing Stress in Organizations How to Develop Positive Managers

    CERN Document Server

    Donaldson-Feilder, Emma; Yarker, Joanna

    2011-01-01

    Preventing Stress in Organizations:How to Develop Positive Managersoffers an innovative, evidence-based approach to help managers prevent and reduce workplace stress in their staff.Provides information on the critical skills managers must develop in order to prevent stress in their staff, and the key ongoing behaviours that promote a healthy work environmentShows practitioners in occupational psychology, HR, Health and Safety and related professions how positive management can be integrated into an organization???s existing practices and processesServes as an essential guide for managers thems

  18. Relative variations of gut microbiota in disordered cholesterol metabolism caused by high-cholesterol diet and host genetics.

    Science.gov (United States)

    Bo, Tao; Shao, Shanshan; Wu, Dongming; Niu, Shaona; Zhao, Jiajun; Gao, Ling

    2017-08-01

    Recent studies performed provide mechanistic insight into effects of the microbiota on cholesterol metabolism, but less focus was given to how cholesterol impacts the gut microbiota. In this study, ApoE -/- Sprague Dawley (SD) rats and their wild-type counterparts (n = 12) were, respectively, allocated for two dietary condition groups (normal chow and high-cholesterol diet). Total 16S rDNA of fecal samples were extracted and sequenced by high-throughput sequencing to determine differences in microbiome composition. Data were collected and performed diversity analysis and phylogenetic analysis. The influence of cholesterol on gut microbiota was discussed by using cholesterol dietary treatment as exogenous cholesterol disorder factor and genetic modification as endogenous metabolic disorder factor. Relative microbial variations were compared to illustrate the causality and correlation of cholesterol and gut microbiota. It turned out comparing to genetically modified rats, exogenous cholesterol intake may play more effective role in changing gut microbiota profile, although the serum cholesterol level of genetically modified rats was even higher. Relative abundance of some representative species showed that the discrepancies due to dietary variation were more obvious, whereas some low abundance species changed because of genetic disorders. Our results partially demonstrated that gut microbiota are relatively more sensitive to dietary variation. Nevertheless, considering the important effect of bacteria in cholesterol metabolism, the influence to gut flora by "genetically caused cholesterol disorder" cannot be overlooked. Manipulation of gut microbiota might be an effective target for preventing cholesterol-related metabolic disorders. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  19. Ethanol Extract from Ulva prolifera Prevents High-Fat Diet-Induced Insulin Resistance, Oxidative Stress, and Inflammation Response in Mice

    Directory of Open Access Journals (Sweden)

    Wei Song

    2018-01-01

    Full Text Available Ulva prolifera is the major causative species in the green tide, a serious marine ecological disaster, which bloomed in the Yellow Sea and the Bohai Sea of China. However, it is also a popular edible seaweed and its extracts exerts anti-inflammatory and antioxidant effects. The present study investigated the effects of ethanol extract of U. prolifera (EUP on insulin sensitivity, inflammatory response, and oxidative stress in high-fat-diet- (HFD- treated mice. HFD-treated mice obtained drinking water containing 2% or 5% EUP. The results showed that EUP supplementation significantly prevented HFD-induced weight gain of liver and fat. EUP supplementation also improved glucose tolerance and insulin resistance in HFD-treated mice. Moreover, EUP supplementation prevented the increased expression of genes involved in triglyceride synthesis and proinflammatory genes and the decreased expression of genes involved in fatty acid oxidation in liver of HFD-treated mice. Furthermore, EUP supplementation decreased reactive oxygen species content, while increasing glutathione content and glutathione peroxidase activity in HFD-treated mice. In conclusion, our results showed that EUP improved insulin resistance and had antilipid accumulation and anti-inflammatory and antioxidative effects on HFD-treated mice. We suggested that U. prolifera extracts may be regarded as potential candidate for the prevention of nonalcoholic fatty liver disease.

  20. DIETARY-CHOLESTEROL INDUCED DOWN-REGULATION OF INTESTINAL 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE-ACTIVITY IS DIMINISHED IN RABBITS WITH HYPERRESPONSE OF SERUM-CHOLESTEROL TO DIETARY-CHOLESTEROL

    NARCIS (Netherlands)

    MEIJER, GW; SMIT, MJ; VANDERPALEN, JGP; KUIPERS, F; VONK, RJ; VANZUTPHEN, BFM; BEYNEN, AC

    Key enzymes of cholesterol metabolism were studied in two inbred strains of rabbits with hyper- or hyporesponse of serum cholesterol to dietary cholesterol. Baseline 3-hydroxy-3-methylglutaryl (HMG)CoA reductase activity in liver was similar in hypo- and hyperresponders, but that in intestine was

  1. Hypolipidemic activity of Phellinus rimosus against triton WR-1339 and high cholesterol diet induced hyperlipidemic rats.

    Science.gov (United States)

    Rony, K A; Ajith, T A; Nima, N; Janardhanan, K K

    2014-03-01

    Patients with the risk for atherosclerotic disease will be targeted to reduce the existing hyperlipidemia. The hypolipidemic activity of Phellinus rimosus was studied using triton WR-1339 and high cholesterol diet (HCD) induced models. The triton induced elevated lipid profile was attenuated by P. rimosus or standard drug atorvastatin. Similarly, administration of P. rimosus along with HCD significantly decline serum triglyceride, total cholesterol, low-density lipoprotein, with elevating the high-density lipoprotein. Thiobarbituric acid reacting substances in heart and liver significantly decreased; where as activity of enzymatic antioxidants and level of reduced glutathione were significantly increased. In both models, P. rimosus extract showed a significant ameliorative effect on the elevated atherogenic index as well as LDL/HDL-C ratio. The hypolipidemic activity of P. rimosus can be ascribed to its inhibitory effect on the liver HMG CoA reductase activity. The results suggest the possible therapeutic potential of this fungus as hypolipidemic agent. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Psychological stress-induced cerebrovascular dysfunction: the role of metabolic syndrome and exercise.

    Science.gov (United States)

    Brooks, Steven; Brnayan, Kayla W; DeVallance, Evan; Skinner, Roy; Lemaster, Kent; Sheets, J Whitney; Pitzer, Christopher R; Asano, Shinichi; Bryner, Randall W; Olfert, I Mark; Frisbee, Jefferson C; Chantler, Paul D

    2018-05-01

    What is the central question of this study? How does chronic stress impact cerebrovascular function and does metabolic syndrome accelerate the cerebrovascular adaptations to stress? What role does exercise training have in preventing cerebrovascular changes to stress and metabolic syndrome? What is the main finding and its importance? Stressful conditions lead to pathological adaptations of the cerebrovasculature via an oxidative nitric oxide pathway, and the presence of metabolic syndrome produces a greater susceptibility to stress-induced cerebrovascular dysfunction. The results also provide insight into the mechanisms that may contribute to the influence of stress and the role of exercise in preventing the negative actions of stress on cerebrovascular function and structure. Chronic unresolvable stress leads to the development of depression and cardiovascular disease. There is a high prevalence of depression with the metabolic syndrome (MetS), but to what extent the MetS concurrent with psychological stress affects cerebrovascular function is unknown. We investigated the differential effect of MetS on cerebrovascular structure/function in rats (16-17 weeks old) following 8 weeks of unpredictable chronic mild stress (UCMS) and whether exercise training could limit any cerebrovascular dysfunction. In healthy lean Zucker rats (LZR), UCMS decreased (28%, P stress and increased production of nitric oxide in the cerebral vessels. In conclusion, UCMS significantly impaired MCA structure and function, but the effects of UCMS were more substantial in OZR vs. LZR. Importantly, aerobic exercise when combined with UCMS prevented the MCA dysfunction through subtle shifts in nitric oxide and oxidative stress in the cerebral microvasculature. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

  3. Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

    Directory of Open Access Journals (Sweden)

    RN Jadeja

    Full Text Available The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS. Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.

  4. Inhibitory effect of Piper betel leaf extracts on copper-mediated LDL oxidation and oxLDL-induced lipid accumulation via inducing reverse cholesterol transport in macrophages.

    Science.gov (United States)

    Ma, Gwo-Chin; Wu, Pei-Fang; Tseng, Hsien-Chun; Chyau, Charng-Cherng; Lu, Hsiu-Chin; Chou, Fen-Pi

    2013-12-15

    Piper betel leaf (PBL) has the biological capabilities of detoxification and can work as an anti-inflammatory agent and an anti-oxidant. In this study, we evaluated the anti-oxidative activity of the extract of Piper betel leaves (PBLs) on the basis of Cu(2+)-mediated oxidation, and its ability to prevent foam cell formation in a model for oxidised low density lipoprotein (oxLDL)-induced lipid accumulation in macrophages. Our data demonstrated that PBLs were able to inhibit LDL oxidation in vitro and are able to reduce the lipid accumulation in macrophages. We showed the underlying mechanisms to be the following: PBLs up-regulated the protein levels of the class A and class B scavenger receptors, the membrane lipid transporter ABCA1, and its upstream regulator Liver X receptor (LXR) in the macrophages exposed to oxLDL. The results suggested that PBLs activated the reverse cholesterol transport mechanism to enhance the metabolism of the oxLDL that could prevent both lipid accumulation and foam cell formation and further minimise the possible damage of vessels caused by the oxLDL. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. An update on the measurement and management of cholesterol with ...

    African Journals Online (AJOL)

    ... and management of cholesterol with specific reference to secondary prevention of ... Serum-cholesterol has emerged as the dominant risk factor for coronary ... reduce the incidence of secondary myocardial infarctions, strokes and death ...

  6. Temozolomide, sirolimus and chloroquine is a new therapeutic combination that synergizes to disrupt lysosomal function and cholesterol homeostasis in GBM cells.

    Science.gov (United States)

    Hsu, Sanford P C; Kuo, John S; Chiang, Hsin-Chien; Wang, Hsin-Ell; Wang, Yu-Shan; Huang, Cheng-Chung; Huang, Yi-Chun; Chi, Mau-Shin; Mehta, Minesh P; Chi, Kwan-Hwa

    2018-01-23

    Glioblastoma (GBM) cells are characterized by high phagocytosis, lipogenesis, exocytosis activities, low autophagy capacity and high lysosomal demand are necessary for survival and invasion. The lysosome stands at the cross roads of lipid biosynthesis, transporting, sorting between exogenous and endogenous cholesterol. We hypothesized that three already approved drugs, the autophagy inducer, sirolimus (rapamycin, Rapa), the autophagy inhibitor, chloroquine (CQ), and DNA alkylating chemotherapy, temozolomide (TMZ) could synergize against GBM. This repurposed triple therapy combination induced GBM apoptosis in vitro and inhibited GBM xenograft growth in vivo . Cytotoxicity is caused by induction of lysosomal membrane permeabilization and release of hydrolases, and may be rescued by cholesterol supplementation. Triple treatment inhibits lysosomal function, prevents cholesterol extraction from low density lipoprotein (LDL), and causes clumping of lysosome associated membrane protein-1 (LAMP-1) and lipid droplets (LD) accumulation. Co-treatment of the cell lines with inhibitor of caspases and cathepsin B only partially reverse of cytotoxicities, while N-acetyl cysteine (NAC) can be more effective. A combination of reactive oxygen species (ROS) generation from cholesterol depletion are the early event of underling mechanism. Cholesterol repletion abolished the ROS production and reversed the cytotoxicity from QRT treatment. The shortage of free cholesterol destabilizes lysosomal membranes converting aborted autophagy to apoptosis through either direct mitochondria damage or cathepsin B release. This promising anti-GBM triple therapy combination severely decreases mitochondrial function, induces lysosome-dependent apoptotic cell death, and is now poised for further clinical testing and validation.

  7. Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory.

    Science.gov (United States)

    Abush, Hila; Akirav, Irit

    2013-07-01

    Repeated stress is one of the environmental factors that precipitates and exacerbates mental illnesses like depression and anxiety as well as cognitive impairments. We have previously shown that cannabinoids can prevent the effects of acute stress on learning and memory. Here we aimed to find whether chronic cannabinoid treatment would alleviate the long-term effects of exposure to chronic restraint stress on memory and plasticity as well as on behavioral and neuroendocrine measures of anxiety and depression. Late adolescent rats were exposed to chronic restraint stress for 2 weeks followed each day by systemic treatment with vehicle or with the CB1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). Thirty days after the last exposure to stress, rats demonstrated impaired long-term potentiation (LTP) in the ventral subiculum-nucleus accumbens (NAc) pathway, impaired performance in the prefrontal cortex (PFC)-dependent object-recognition task and the hippocampal-dependent spatial version of this task, increased anxiety levels, and significantly reduced expression of glucocorticoid receptors (GRs) in the amygdala, hippocampus, PFC, and NAc. Chronic WIN55,212-2 administration prevented the stress-induced impairment in LTP levels and in the spatial task, with no effect on stress-induced alterations in unconditioned anxiety levels or GR levels. The CB1 antagonist AM251 (0.3 mg/kg) prevented the ameliorating effects of WIN55,212-2 on LTP and short-term memory. Hence, the beneficial effects of WIN55,212-2 on memory and plasticity are mediated by CB1 receptors and are not mediated by alterations in GR levels in the brain areas tested. Our findings suggest that cannabinoid receptor activation could represent a novel approach to the treatment of cognitive deficits that accompany a variety of stress-related neuropsychiatric disorders.

  8. Evaluation of the Potential of Brazilian Propolis against UV-Induced Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yris Maria Fonseca

    2011-01-01

    Full Text Available This study investigated the potential use of topically and orally administered propolis extracts to prevent UV irradiation-induced oxidative stress in skin. The results illustrated that green propolis extract (GPE contained greater amounts of polyphenols, coumaric acid, drupanin, baccharin and artepillin C than did brown propolis extract (BPE. GPE showed higher antioxidant activity than BPE when the IC50 (concentration that caused 50% inhibition values were compared. Interesting, the oral treatment of hairless mice demonstrated a recovery of 30.0% for GPE and 22.8% for BPE with respect to UV irradiation-induced GSH depletion. The topical pretreatment of animals with both propolis extract solutions recovered around 14.0% of the depleted GSH. However, the employed treatments did not inhibit the increase of cutaneous proteinase secretion/activity caused by irradiation. These findings indicate that despite differences in composition and antioxidant properties, GPE and BPE both successfully prevent UV-induced GSH depletion in vivo and are both promising antioxidant systems against oxidative stress in skin. Based on these findings, complementary studies should be performed to enhance our understanding of the protective effects of propolis extracts in skin.

  9. Blockade of AT1 type receptors for angiotensin II prevents cardiac microvascular fibrosis induced by chronic stress in Sprague-Dawley rats.

    Science.gov (United States)

    Firoozmand, Lília Taddeo; Sanches, Andrea; Damaceno-Rodrigues, Nilsa Regina; Perez, Juliana Dinéia; Aragão, Danielle Sanches; Rosa, Rodolfo Mattar; Marcondes, Fernanda Klein; Casarini, Dulce Elena; Caldini, Elia Garcia; Cunha, Tatiana Sousa

    2018-04-20

    To test the effects of chronic-stress on the cardiovascular system, the model of chronic mild unpredictable stress (CMS) has been widely used. The CMS protocol consists of the random, intermittent, and unpredictable exposure of laboratory animals to a variety of stressors, during 3 consecutive weeks. In this study, we tested the hypothesis that exposure to the CMS protocol leads to left ventricle microcirculatory remodeling that can be attenuated by angiotensin II receptor blockade. Male Sprague-Dawley rats were randomly assigned into four groups: Control, Stress, Control + losartan, and Stress + losartan (N = 6, each group, losartan: 20 mg/kg/day). The rats were euthanized 15 days after CMS exposure, and blood samples and left ventricle were collected. Rats submitted to CMS presented increased glycemia, corticosterone, noradrenaline and adrenaline concentration, and losartan reduced the concentration of the circulating amines. Cardiac angiotensin II, measured by high-performance liquid chromatography (HPLC), was significantly increased in the CMS group, and losartan treatment reduced it, while angiotensin 1-7 was significantly higher in the CMS losartan-treated group as compared with CMS. Histological analysis, verified by transmission electron microscopy, showed that rats exposed to CMS presented increased perivascular collagen and losartan effectively prevented the development of this process. Hence, CMS induced a state of microvascular disease, with increased perivascular collagen deposition, that may be the trigger for further development of cardiovascular disease. In this case, CMS fibrosis is associated with increased production of catecholamines and with a disruption of renin-angiotensin system balance, which can be prevented by angiotensin II receptor blockade.

  10. Chloride secretion induced by rotavirus is oxidative stress-dependent and inhibited by Saccharomyces boulardii in human enterocytes.

    Directory of Open Access Journals (Sweden)

    Vittoria Buccigrossi

    Full Text Available Rotavirus (RV infection causes watery diarrhea via multiple mechanisms, primarily chloride secretion in intestinal epithelial cell. The chloride secretion largely depends on non-structural protein 4 (NSP4 enterotoxic activity in human enterocytes through mechanisms that have not been defined. Redox imbalance is a common event in cells infected by viruses, but the role of oxidative stress in RV infection is unknown. RV SA11 induced chloride secretion in association with an increase in reactive oxygen species (ROS in Caco-2 cells. The ratio between reduced (GSH and oxidized (GSSG glutathione was decreased by RV. The same effects were observed when purified NSP4 was added to Caco-2 cells. N-acetylcysteine (NAC, a potent antioxidant, strongly inhibited the increase in ROS and GSH imbalance. These results suggest a link between oxidative stress and RV-induced diarrhea. Because Saccharomyces boulardii (Sb has been effectively used to treat RV diarrhea, we tested its effects on RV-infected cells. Sb supernatant prevented RV-induced oxidative stress and strongly inhibited chloride secretion in Caco-2 cells. These results were confirmed in an organ culture model using human intestinal biopsies, demonstrating that chloride secretion induced by RV-NSP4 is oxidative stress-dependent and is inhibited by Sb, which produces soluble metabolites that prevent oxidative stress. The results of this study provide novel insights into RV-induced diarrhea and the efficacy of probiotics.

  11. Macrophage Migration Inhibitory Factor Secretion Is Induced by Ionizing Radiation and Oxidative Stress in Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Yashi Gupta

    Full Text Available The macrophage migration inhibitory factor (MIF has been increasingly implicated in cancer development and progression by promoting inflammation, angiogenesis, tumor cell survival and immune suppression. MIF is overexpressed in a variety of solid tumor types in part due to its responsiveness to hypoxia inducible factor (HIF driven transcriptional activation. MIF secretion, however, is a poorly understood process owing to the fact that MIF is a leaderless polypeptide that follows a non-classical secretory pathway. Better understanding of MIF processing and release could have therapeutic implications. Here, we have discovered that ionizing radiation (IR and other DNA damaging stresses can induce robust MIF secretion in several cancer cell lines. MIF secretion by IR appears independent of ABCA1, a cholesterol efflux pump that has been implicated previously in MIF secretion. However, MIF secretion is robustly induced by oxidative stress. Importantly, MIF secretion can be observed both in cell culture models as well as in tumors in mice in vivo. Rapid depletion of MIF from tumor cells observed immunohistochemically is coincident with elevated circulating MIF detected in the blood sera of irradiated mice. Given the robust tumor promoting activities of MIF, our results suggest that an innate host response to genotoxic stress may mitigate the beneficial effects of cancer therapy, and that MIF inhibition may improve therapeutic responses.

  12. Cholesterol complacency in Australia: time to revisit the basics of cardiovascular disease prevention.

    Science.gov (United States)

    Carrington, Melinda J; Retegan, Claudia; Johnston, Colin I; Jennings, Garry L; Stewart, Simon

    2009-03-01

    Community awareness of the importance of hypercholesterolemia and the need for appropriate therapy is an important part of global efforts to reduce the population burden of cardiovascular disease. The aim of this study was to assess the knowledge and attitudes about cholesterol and to determine adherence to taking cholesterol-lowering medication among patients at high risk for cardiovascular events. In spite of the availability of lifestyle and medical treatments for lipid management, an estimated 50% of adult Australians (6.4 million) remain at risk for a cardiovascular-related event because they have total blood cholesterol levels which exceed recommended limits. It is within this context that a significant gap remains in meeting cholesterol goals, despite easy to meet targets with readily available therapeutic options. A two-page national self-report postal survey was conducted from August-October 2006. A total of 508 Australian adults previously treated for hypercholesterolemia were surveyed to determine their understanding about cholesterol and their adherence to treatment. The mean age of participants was 67 (SD 10) years (72% male). Many participants (72%) were at risk of a cardiovascular event based on a prior history and 18% had type II diabetes. Participants had been prescribed lipid-lowering therapy (94% statin therapy) for an average of 10 years and visited their general practitioner on average three times per year. For those who knew their most recent cholesterol reading (67%), the total cholesterol was on average 4.5 (SD 1.1) mmol/l. This level was above the recommended limits for 40% of participants. Overall, 85% of participants reported knowing that there was high- and low-density lipoprotein forms of cholesterol, but only 56% and 38%, respectively, said that they understood or showed signs of clearly understanding the different types of cholesterol when their knowledge was assessed further. On the whole, therefore, participants had a limited

  13. The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation.

    Science.gov (United States)

    Feeney, Eoin R; McAuley, Nuala; O'Halloran, Jane A; Rock, Clare; Low, Justin; Satchell, Claudette S; Lambert, John S; Sheehan, Gerald J; Mallon, Patrick W G

    2013-02-15

    Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk and reduced high-density lipoprotein cholesterol (HDL-c). In vitro, HIV impairs monocyte-macrophage cholesterol efflux, a major determinant of circulating HDL-c, by increasing ABCA1 degradation, with compensatory upregulation of ABCA1 messenger RNA (mRNA). We examined expression of genes involved in cholesterol uptake, metabolism, and efflux in monocytes from 22 HIV-positive subjects on antiretroviral therapy (ART-Treated), 30 untreated HIV-positive subjects (ART-Naive), and 22 HIV-negative controls (HIV-Neg). HDL-c was lower and expression of ABCA1 mRNA was higher in ART-Naive subjects than in both ART-Treated and HIV-Neg subjects (both P ART-Treated and ART-Naive subjects than in HIV-Neg controls. In vivo, increased monocyte ABCA1 expression in untreated HIV-infected patients and normalization of ABCA1 expression with virological suppression by ART supports direct HIV-induced impairment of cholesterol efflux previously demonstrated in vitro. However, decreased expression of cholesterol sensing, uptake, and synthesis genes in both untreated and treated HIV infection suggests that both HIV and ART affect monocyte cholesterol metabolism in a pattern consistent with accumulation of intramonocyte cholesterol.

  14. Histone deacetylase inhibition decreases cholesterol levels in neuronal cells by modulating key genes in cholesterol synthesis, uptake and efflux.

    Directory of Open Access Journals (Sweden)

    Maria João Nunes

    Full Text Available Cholesterol is an essential component of the central nervous system and increasing evidence suggests an association between brain cholesterol metabolism dysfunction and the onset of neurodegenerative disorders. Interestingly, histone deacetylase inhibitors (HDACi such as trichostatin A (TSA are emerging as promising therapeutic approaches in neurodegenerative diseases, but their effect on brain cholesterol metabolism is poorly understood. We have previously demonstrated that HDACi up-regulate CYP46A1 gene transcription, a key enzyme in neuronal cholesterol homeostasis. In this study, TSA was shown to modulate the transcription of other genes involved in cholesterol metabolism in human neuroblastoma cells, namely by up-regulating genes that control cholesterol efflux and down-regulating genes involved in cholesterol synthesis and uptake, thus leading to an overall decrease in total cholesterol content. Furthermore, co-treatment with the amphipathic drug U18666A that can mimic the intracellular cholesterol accumulation observed in cells of Niemman-Pick type C patients, revealed that TSA can ameliorate the phenotype induced by pathological cholesterol accumulation, by restoring the expression of key genes involved in cholesterol synthesis, uptake and efflux and promoting lysosomal cholesterol redistribution. These results clarify the role of TSA in the modulation of neuronal cholesterol metabolism at the transcriptional level, and emphasize the idea of HDAC inhibition as a promising therapeutic tool in neurodegenerative disorders with impaired cholesterol metabolism.

  15. MooPoong (Gye Young Jeong) increases HDL-cholesterol but decreases LDL cholesterol and body-weight.

    Science.gov (United States)

    Chung, Hwan-Suck; Hong, Seung-Heon; Do, Keum-Rok; Rhee, Hyung-Koo; Jung, Sung-Ki; Hwang, Woo-Jun; Kim, Hyung-Min

    2004-05-01

    MooPoong (MP, Gye Young Jeong), a Korean traditional wine, has been used as a prevention and treatment agent of blood circulatory trouble. To evaluate such an effect of MP, we analyzed whether the plasma levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and body weight change after rats were fed on high fat diet with MP for 8 weeks. Plasma LDL cholesterol level decreased by 5.6% in 0.128% MP treated group and by 11.1% in 0.640% MP treated group. However, HDL cholesterol was increased by 6.7% in 0.128% MP diet group and 33.3% in 0.640% MP diet group. In addition, there was a significant weight loss in the MP treated group compared with the high-fat diet group (P < 0.05). Our findings indicate that MP may contain compounds with actions which can treat blood circulatory trouble as well as overweight.

  16. Influence of Water Quality on Cholesterol-Induced Tau Pathology: Preliminary Data

    Directory of Open Access Journals (Sweden)

    D. Larry Sparks

    2011-01-01

    Full Text Available The studies employed the cholesterol-fed rabbit model of Alzheimer's disease (AD to investigate the relationship between AD-like neurofibrillary tangle (NFT neuropathology and tau protein levels as the main component of NFT. We measured brain and plasma tau levels and semiquantified NFT-like neuropathology in cholesterol-fed rabbits administered drinking water of varying quality (distilled, tap, and distilled+copper compared to animals receiving normal chow and local tap water. Total tau levels in plasma were increased in all cholesterol-fed rabbits compared to animals on normal chow, regardless of quality of water. In contrast, increased tau in brain and increased AT8 immunoreactive NFT-like lesions were greatest in cholesterol-fed rabbits administered distilled water. A substantial decrease in brain tau and incidence and density of AT8 immunoreactive NFT-like lesions occurred in cholesterol-fed rabbits administered copper water, and an even greater decrease was observed in cholesterol-fed animals on local tap water. These studies suggest the possibility that circulating tau could be the source of the tau accumulating in the brain.

  17. Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity.

    Science.gov (United States)

    Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

    2016-05-23

    The uroguanylin-GUCY2C gut-brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ER(T2)-Rosa-STOP(loxP/loxP)-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms

  18. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    Science.gov (United States)

    Alsop, Richard; Barrett, Matthew; Zheng, Sonbo; Dies, Hannah; Rheinstadter, Maikel

    2014-03-01

    Aspirin (ASA) is often prescribed for patients with high levels of cholesterol for the secondary prevention of myocardial events, a regimen known as the Low-Dose Aspirin Therapy. We have recently shown that Aspirin partitions in lipid bilayers. However, a direct interplay between ASA and cholesterol has not been investigated. Cholesterol is known to insert itself into the membrane in a dispersed state at moderate concentrations (under ~37.5%) and decrease fluidity of membranes. We prepared model lipid membranes containing varying amounts of both ASA and cholesterol molecules. The structure of the bilayers as a function of ASA and cholesterol concentration was determined using high-resolution X-ray diffraction. At cholesterol levels of more than 40mol%, immiscible cholesterol plaques formed. Adding ASA to the membranes was found to dissolve the cholesterol plaques, leading to a fluid lipid bilayer structure. We present first direct evidence for an interaction between ASA and cholesterol on the level of the cell membrane.

  19. Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers

    Directory of Open Access Journals (Sweden)

    Ravi Varatharajalu

    2016-01-01

    Full Text Available Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories from ω-3 polyunsaturated fatty acids (PUFA and Lieber-deCarli high menhaden (13.8% of total calories from ω-3 PUFA alcohol-liquid (5% diets supplemented with or without curcumin (150 mg/kg/day for 8 weeks. Treatment with curcumin protected against high ω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1 mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to high ω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with high ω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and high ω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis.

  20. Uranium induces oxidative stress in lung epithelial cells

    International Nuclear Information System (INIS)

    Periyakaruppan, Adaikkappan; Kumar, Felix; Sarkar, Shubhashish; Sharma, Chidananda S.; Ramesh, Govindarajan T.

    2007-01-01

    Uranium compounds are widely used in the nuclear fuel cycle, antitank weapons, tank armor, and also as a pigment to color ceramics and glass. Effective management of waste uranium compounds is necessary to prevent exposure to avoid adverse health effects on the population. Health risks associated with uranium exposure includes kidney disease and respiratory disorders. In addition, several published results have shown uranium or depleted uranium causes DNA damage, mutagenicity, cancer and neurological defects. In the current study, uranium toxicity was evaluated in rat lung epithelial cells. The study shows uranium induces significant oxidative stress in rat lung epithelial cells followed by concomitant decrease in the antioxidant potential of the cells. Treatment with uranium to rat lung epithelial cells also decreased cell proliferation after 72 h in culture. The decrease in cell proliferation was attributed to loss of total glutathione and superoxide dismutase in the presence of uranium. Thus the results indicate the ineffectiveness of antioxidant system's response to the oxidative stress induced by uranium in the cells. (orig.)

  1. Membrane cholesterol effect on the 5-HT2A receptor: Insights into the lipid-induced modulation of an antipsychotic drug target.

    Science.gov (United States)

    Ramírez-Anguita, Juan Manuel; Rodríguez-Espigares, Ismael; Guixà-González, Ramon; Bruno, Agostino; Torrens-Fontanals, Mariona; Varela-Rial, Alejandro; Selent, Jana

    2018-01-01

    The serotonin 5-hydroxytryptamine 2A (5-HT 2A ) receptor is a G-protein-coupled receptor (GPCR) relevant for the treatment of CNS disorders. In this regard, neuronal membrane composition in the brain plays a crucial role in the modulation of the receptor functioning. Since cholesterol is an essential component of neuronal membranes, we have studied its effect on the 5-HT 2A receptor dynamics through all-atom MD simulations. We find that the presence of cholesterol in the membrane increases receptor conformational variability in most receptor segments. Importantly, detailed structural analysis indicates that conformational variability goes along with the destabilization of hydrogen bonding networks not only within the receptor but also between receptor and lipids. In addition to increased conformational variability, we also find receptor segments with reduced variability. Our analysis suggests that this increased stabilization is the result of stabilizing effects of tightly bound cholesterol molecules to the receptor surface. Our finding contributes to a better understanding of membrane-induced alterations of receptor dynamics and points to cholesterol-induced stabilizing and destabilizing effects on the conformational variability of GPCRs. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  2. Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis.

    Science.gov (United States)

    Song, Yu-Feng; Hogstrand, Christer; Wei, Chuan-Chuan; Wu, Kun; Pan, Ya-Xiong; Luo, Zhi

    2017-09-01

    The present study was performed to determine the effect of Zn exposure influencing endoplasmic reticulum (ER) stress, explore the underlying molecular mechanism of Zn-induced hepatic lipolysis in a fish species of significance for aquaculture, yellow catfish Pelteobagrus fulvidraco. We found that waterborne Zn exposure evoked ER stress and unfolded protein response (UPR), and activated cAMP/PKA pathway, and up-regulated hepatic lipolysis. The increase in ER stress and lipolysis were associated with activation of cAMP/PKA signaling pathway. Zn also induced an increase in intracellular Ca 2+ level, which could be partially prevented by dantrolene (RyR receptor inhibitor) and 2-APB (IP3 receptor inhibitor), demonstrating that the disturbed Ca 2+ homeostasis in ER contributed to ER stress and dysregulation of lipolysis. Inhibition of ER stress by PBA attenuated UPR, inhibited the activation of cAMP/PKA pathway and resulted in down-regulation of lipolysis. Inhibition of protein kinase RNA-activated-like ER kinase (PERK) by GSK2656157 and inositol-requiring enzyme (IRE) by STF-083010 differentially influenced Zn-induced changes of lipid metabolism, indicating that PERK and IRE pathways played different regulatory roles in Zn-induced lipolysis. Inhibition of PKA by H89 blocked the Zn-induced activation of cAMP/PKA pathway with a concomitant inhibition of ER stress-mediated lipolysis. Taken together, our findings highlight the importance of the ER stress-cAMP/PKA axis in Zn-induced lipolysis, which provides new insights into Zn toxicology in fish and probably in other vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Critical Role of Endoplasmic Reticulum Stress in Chronic Intermittent Hypoxia-Induced Deficits in Synaptic Plasticity and Long-Term Memory.

    Science.gov (United States)

    Xu, Lin-Hao; Xie, Hui; Shi, Zhi-Hui; Du, Li-Da; Wing, Yun-Kwok; Li, Albert M; Ke, Ya; Yung, Wing-Ho

    2015-09-20

    This study examined the role of endoplasmic reticulum (ER) stress in mediating chronic intermittent hypoxia (IH)-induced neurocognitive deficits. We designed experiments to demonstrate that ER stress is initiated in the hippocampus under chronic IH and determined its role in apoptotic cell death, impaired synaptic structure and plasticity, and memory deficits. Two weeks of IH disrupted ER fine structure and upregulated ER stress markers, glucose-regulated protein 78, caspase-12, and C/EBP homologous protein, in the hippocampus, which could be suppressed by ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid. Meanwhile, ER stress induced apoptosis via decreased Bcl-2, promoted reactive oxygen species production, and increased malondialdehyde formation and protein carbonyl, as well as suppressed mitochondrial function. These effects were largely prevented by ER stress inhibitors. On the other hand, suppression of oxidative stress could reduce ER stress. In addition, the length of the synaptic active zone and number of mature spines were reduced by IH. Long-term recognition memory and spatial memory were also impaired, which was accompanied by reduced long-term potentiation in the Schaffer collateral pathway. These effects were prevented by coadministration of the TUDCA. These results show that ER stress plays a critical role in underlying memory deficits in obstructive sleep apnea (OSA)-associated IH. Attenuators of ER stress may serve as novel adjunct therapeutic agents for ameliorating OSA-induced neurocognitive impairment.

  4. Stress-induced decrease of uterine blood flow in sheep is mediated by alpha 1-adrenergic receptors.

    Science.gov (United States)

    Dreiling, Michelle; Bischoff, Sabine; Schiffner, Rene; Rupprecht, Sven; Kiehntopf, Michael; Schubert, Harald; Witte, Otto W; Nathanielsz, Peter W; Schwab, Matthias; Rakers, Florian

    2016-09-01

    Prenatal maternal stress can be transferred to the fetus via a catecholamine-dependent decrease of uterine blood flow (UBF). However, it is unclear which group of adrenergic receptors mediates this mechanism of maternal-fetal stress transfer. We hypothesized that in sheep, alpha 1-adrenergic receptors may play a key role in catecholamine mediated UBF decrease, as these receptors are mainly involved in peripheral vasoconstriction and are present in significant number in the uterine vasculature. After chronic instrumentation at 125 ± 1 days of gestation (dGA; term 150 dGA), nine pregnant sheep were exposed at 130 ± 1 dGA to acute isolation stress for one hour without visual, tactile, or auditory contact with their flockmates. UBF, blood pressure (BP), heart rate (HR), stress hormones, and blood gases were determined before and during this isolation challenge. Twenty-four hours later, experiments were repeated during alpha 1-adrenergic receptor blockage induced by a continuous intravenous infusion of urapidil. In both experiments, ewes reacted to isolation with an increase in serum norepinephrine, cortisol, BP, and HR as typical signs of activation of sympatho-adrenal and the hypothalamic-pituitary-adrenal axis. Stress-induced UBF decrease was prevented by alpha 1-adrenergic receptor blockage. We conclude that UBF decrease induced by maternal stress in sheep is mediated by alpha 1-adrenergic receptors. Future studies investigating prevention strategies of impact of prenatal maternal stress on fetal health should consider selective blockage of alpha 1-receptors to interrupt maternal-fetal stress transfer mediated by utero-placental malperfusion.

  5. Expression profile of mce4 operon of Mycobacterium tuberculosis following environmental stress.

    Science.gov (United States)

    Rathor, Nisha; Garima, Kushal; Sharma, Naresh Kumar; Narang, Anshika; Varma-Basil, Mandira; Bose, Mridula

    2016-09-01

    The mce4 operon is one of the four mce operons with eight genes (yrbE4A, yrbE4B, mce4A, mce4B, mce4C, mce4D, mce4E and mce4F) of Mycobacterium tuberculosis. It expresses in the later phase of infection and imports cholesterol for long term survival of the bacilli. To cause latent infection, M. tuberculosis undergoes metabolic reprogramming of its genes to survive in the hostile environment like low availability of oxygen and nutrition depletion inside the host. To analyze real time expression profile of mce4 operon under various stress conditions. M. tuberculosis H37Rv was exposed to surface stress (0.1% SDS for 30min and 90min in late log and stationary phase of culture), hypoxia (5, 10, 15 and 20days) and grown in the presence of either glycerol or cholesterol as sole source of carbon. The expression profile of genes of mce4 operon was analyzed by real time PCR. Surface stress induced expression of mce4C and yrbE4B in late log phase on 30min and 90min exposure respectively. The SDS exposure for 30min induced mce4C, mce4D and mce4F in stationary phase. All eight genes were induced significantly on 10th and 15th days of hypoxia and in the presence of cholesterol. Hypoxia and cholesterol are potent factors for the expression of mce4 operon of M. tuberculosis. Copyright © 2016. Published by Elsevier Ltd.

  6. Hypercholesterolemia aggravates myocardial ischemia reperfusion injury via activating endoplasmic reticulum stress-mediated apoptosis.

    Science.gov (United States)

    Wu, Nan; Zhang, Xiaowen; Jia, Pengyu; Jia, Dalin

    2015-12-01

    The effect of hypercholesterolemia on myocardial ischemia reperfusion injury (MIRI) is in controversy and the underlying mechanism is still not well understood. In the present study, we firstly detected the effects of hypercholesterolemia on MIRI and the role of endoplasmic reticulum (ER) stress-mediated apoptosis pathway in this process. The infarct size was determined by TTC staining, and apoptosis was measured by the TUNEL method. The marker proteins of ER stress response and ER stress-mediated apoptosis pathway were detected by Western blot. The results showed that high cholesterol diet-induced hypercholesterolemia significantly increased the myocardial infarct size, the release of myocardium enzyme and the ratio of apoptosis, but did not affect the recovery of cardiac function. Moreover, hypercholesterolemia also remarkably up-regulated the expressions of ER stress markers (glucose-regulated protein 78 and calreticulin) and critical molecules in ER stress-mediated apoptosis pathway (CHOP, caspase 12, phospho-JNK). In conclusion, our study demonstrated that hypercholesterolemia enhanced myocardial vulnerability/sensitivity to ischemia reperfusion injury involved in aggravation the ER stress and activation of ER stress-mediated apoptosis pathway and it gave us a new insight into the underlying mechanisms associated with hypercholesterolemia-induced exaggerated MIRI and also provided a novel target for preventing MIRI in the presence of hypercholesterolemia. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Voluntary exercise increases cholesterol efflux but not macrophage reverse cholesterol transport in vivo in mice

    Directory of Open Access Journals (Sweden)

    Kuipers Folkert

    2010-07-01

    Full Text Available Abstract Physical exercise beneficially impacts on the plasma lipoprotein profile as well as on the incidence of cardiovascular events and is therefore recommended in primary and secondary prevention strategies against atherosclerotic cardiovascular disease. However, the underlying mechanisms of the protective effect of exercise remain largely unknown. Therefore, the present study tested the hypothesis that voluntary exercise in mice impacts on cholesterol efflux and in vivo reverse cholesterol transport (RCT. After two weeks of voluntary wheel running (average 10.1 ± 1.4 km/day plasma triglycerides were lower (p

  8. Stress corrosion cracking mitigation by ultrasound induced cavitation technique

    Energy Technology Data Exchange (ETDEWEB)

    Fong, C.; Lee, Y.C. [Industrial Technology Research Inst., Taiwan (China); Yeh, T.K. [National Tsing Hua Univ., Taiwan (China)

    2014-07-01

    Cavitation is usually considered as a damaging mechanism under erosion corrosion condition. However, if used appropriately, cavitation can be applied as a peening technique for surface stress modification process. The aim of surface stress modification is to alter the stress state of processed surface through direct or indirect thermo-mechanical treatments to reduce cracking problems initiated from surface. Ultrasonic devices are used to generate cavitation bubbles which when collapse will produce high intensity shock waves and high velocity micro-jet streams. The cavitation impact when properly controlled will create plastically deformed compressive layers in nearby surfaces and minimize cracking susceptibility in corrosive environments. This study is to investigate the effectiveness of Ultrasound Induced Cavitation (UIC) technique in surface stress improvement. Ultrasonic cavitation treatment of SS304 stainless steel under pure water is carried out with different controlling parameters. The cavitation impact on SS304 surface is measured in terms of surface roughness, surface strain, hardness, and microstructural characteristics. The in-depth residual stress distribution and crack mitigation effect are also evaluated. Test result indicates ultrasound induced cavitation treatment only has minor effect on surface physical characteristics. The extent of compressive stress produced on top surface exceeds the yield strength and can reach a depth above 150 μm. The maximum surface strain measured is generally below 20%, which is not considered detrimental to accelerate crack initiation. Stress corrosion verification tests show UIC treatment is capable in preventing environmental assisted cracking of stainless steels in severely corrosive conditions. In view of the test results, UIC technique has demonstrated to be a low cost, low contaminating, and effective surface stress improvement technology. (author)

  9. Stress corrosion cracking mitigation by ultrasound induced cavitation technique

    International Nuclear Information System (INIS)

    Fong, C.; Lee, Y.C.; Yeh, T.K.

    2014-01-01

    Cavitation is usually considered as a damaging mechanism under erosion corrosion condition. However, if used appropriately, cavitation can be applied as a peening technique for surface stress modification process. The aim of surface stress modification is to alter the stress state of processed surface through direct or indirect thermo-mechanical treatments to reduce cracking problems initiated from surface. Ultrasonic devices are used to generate cavitation bubbles which when collapse will produce high intensity shock waves and high velocity micro-jet streams. The cavitation impact when properly controlled will create plastically deformed compressive layers in nearby surfaces and minimize cracking susceptibility in corrosive environments. This study is to investigate the effectiveness of Ultrasound Induced Cavitation (UIC) technique in surface stress improvement. Ultrasonic cavitation treatment of SS304 stainless steel under pure water is carried out with different controlling parameters. The cavitation impact on SS304 surface is measured in terms of surface roughness, surface strain, hardness, and microstructural characteristics. The in-depth residual stress distribution and crack mitigation effect are also evaluated. Test result indicates ultrasound induced cavitation treatment only has minor effect on surface physical characteristics. The extent of compressive stress produced on top surface exceeds the yield strength and can reach a depth above 150 μm. The maximum surface strain measured is generally below 20%, which is not considered detrimental to accelerate crack initiation. Stress corrosion verification tests show UIC treatment is capable in preventing environmental assisted cracking of stainless steels in severely corrosive conditions. In view of the test results, UIC technique has demonstrated to be a low cost, low contaminating, and effective surface stress improvement technology. (author)

  10. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne

    2011-01-01

    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

  11. A unique polysaccharide purified from Hericium erinaceus mycelium prevents oxidative stress induced by H2O2 in human gastric mucosa epithelium cell.

    Science.gov (United States)

    Wang, Mingxing; Kanako, Nakajima; Zhang, Yanqiu; Xiao, Xulang; Gao, Qipin; Tetsuya, Konishi

    2017-01-01

    Hericium erinaceus (HE) has been used both as a traditional Chinese medicine and home remedy for treatment of gastric and duodenal ulcers and gastritis. EP-1, a purified polysaccharide isolated from HE mycelium, has recently been identified as the active component responsible for HE anti-gastritis activity. Because oxidative stress has been implicated as a pathogenic cause of gastritis and gastric ulcers, EP-1 antioxidant properties were systematically examined in vitro using the human gastric mucosal epithelial cell line, GES-1. Results showed that EP-1 possessed higher oxygen radical absorbance capacity (ORAC) and 2-3 times higher ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals than a hot water extract of commercially available HE fruiting body. A crude mycelial polysaccharide (CMPS) extract of HE, from which EP-1 was purified, showed slightly stronger radical scavenging activity and ORAC than EP-1, with the exception of DPPH-scavenging activity. Antioxidant activities of these extracts were further studied using hydrogen peroxide (H2O2)-abused GES-1 cells; EP-1 dose-dependently preserved cell viability of abused cells as assessed via MTT assay. Moreover, FACS analysis revealed that EP-1 prevented H2O2-induced apoptotic cell death by inhibiting activation of apoptotic cellular signals within mitochondria-dependent apoptotic pathways. CMPS also prevented H2O2-induced oxidative stress, but to a lesser degree than did EP-1, even though CMPS exhibited comparable or stronger in vitro antioxidant activity than did EP-1.

  12. A unique polysaccharide purified from Hericium erinaceus mycelium prevents oxidative stress induced by H2O2 in human gastric mucosa epithelium cell.

    Directory of Open Access Journals (Sweden)

    Mingxing Wang

    Full Text Available Hericium erinaceus (HE has been used both as a traditional Chinese medicine and home remedy for treatment of gastric and duodenal ulcers and gastritis. EP-1, a purified polysaccharide isolated from HE mycelium, has recently been identified as the active component responsible for HE anti-gastritis activity. Because oxidative stress has been implicated as a pathogenic cause of gastritis and gastric ulcers, EP-1 antioxidant properties were systematically examined in vitro using the human gastric mucosal epithelial cell line, GES-1. Results showed that EP-1 possessed higher oxygen radical absorbance capacity (ORAC and 2-3 times higher ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH, superoxide and hydroxyl radicals than a hot water extract of commercially available HE fruiting body. A crude mycelial polysaccharide (CMPS extract of HE, from which EP-1 was purified, showed slightly stronger radical scavenging activity and ORAC than EP-1, with the exception of DPPH-scavenging activity. Antioxidant activities of these extracts were further studied using hydrogen peroxide (H2O2-abused GES-1 cells; EP-1 dose-dependently preserved cell viability of abused cells as assessed via MTT assay. Moreover, FACS analysis revealed that EP-1 prevented H2O2-induced apoptotic cell death by inhibiting activation of apoptotic cellular signals within mitochondria-dependent apoptotic pathways. CMPS also prevented H2O2-induced oxidative stress, but to a lesser degree than did EP-1, even though CMPS exhibited comparable or stronger in vitro antioxidant activity than did EP-1.

  13. The CRF₁ receptor antagonist SSR125543 prevents stress-induced long-lasting sleep disturbances in a mouse model of PTSD: comparison with paroxetine and d-cycloserine.

    Science.gov (United States)

    Philbert, Julie; Beeské, Sandra; Belzung, Catherine; Griebel, Guy

    2015-02-15

    The selective CRF₁ (corticotropin releasing factor type 1) receptor antagonist SSR125543 has been previously shown to attenuate the long-term behavioral and electrophysiological effects produced by traumatic stress exposure in mice. Sleep disturbances are one of the most commonly reported symptoms by people with post-traumatic stress disorder (PTSD). The present study aims at investigating whether SSR125543 (10 mg/kg/day/i.p. for 2 weeks) is able to attenuate sleep/wakefulness impairment induced by traumatic stress exposure in a model of PTSD in mice using electroencephalographic (EEG) analysis. Effects of SSR125543 were compared to those of the 5-HT reuptake inhibitor, paroxetine (10 mg/kg/day/i.p.), and the partial N-methyl-d-aspartate (NMDA) receptor agonist, d-cycloserine (10 mg/kg/day/i.p.), two compounds which have demonstrated clinical efficacy against PTSD. Baseline EEG recording was performed in the home cage for 6h prior to the application of two electric foot-shocks of 1.5 mA. Drugs were administered from day 1 post-stress to the day preceding the second EEG recording session, performed 14 days later. Results showed that at day 14 post-stress, shocked mice displayed sleep fragmentation as shown by an increase in the occurrence of both non-rapid eye movement (NREM) sleep and wakefulness bouts. The duration of wakefulness, NREM and REM sleep were not significantly affected. The stress-induced effects were prevented by repeated administration of SSR125543, paroxetine and D-cycloserine. These findings confirm further that the CRF₁ receptor antagonist SSR125543 is able to attenuate the deleterious effects of traumatic stress exposure. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Statin treatment and stroke outcome in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

    DEFF Research Database (Denmark)

    Goldstein, L.B.; Amarenco, P.; Zivin, J.

    2009-01-01

    BACKGROUND AND PURPOSE: Laboratory experiments suggest statins reduce stroke severity and improve outcomes. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial was a placebo-controlled, randomized trial designed to determine whether treatment with atorvastatin reduces...... or 4), moderate (modified Rankin Scale score 3 or 2), and mild (modified Rankin Scale score 1 or 0) outcome ischemic strokes and transient ischemic attacks and an increase in the proportion of event-free subjects randomized to atorvastatin (P

  15. Protective Effect of Wheat Peptides against Indomethacin-Induced Oxidative Stress in IEC-6 Cells

    Directory of Open Access Journals (Sweden)

    Hong Yin

    2014-01-01

    Full Text Available Recent studies have demonstrated that wheat peptides protected rats against non-steroidal anti-inflammatory drugs-induced small intestinal epithelial cells damage, but the mechanism of action is unclear. In the present study, an indomethacin-induced oxidative stress model was used to investigate the effect of wheat peptides on the nuclear factor-κB(NF-κB-inducible nitric oxide synthase-nitric oxide signal pathway in intestinal epithelial cells-6 cells. IEC-6 cells were treated with wheat peptides (0, 125, 500 and 2000 mg/L for 24 h, followed by 90 mg/L indomethacin for 12 h. Wheat peptides significantly attenuated the indomethacin-induced decrease in superoxide dismutase and glutathione peroxidase activity. Wheat peptides at 2000 mg/L markedly decreased the expression of the NF-κB in response to indomethacin-induced oxidative stress. This study demonstrated that the addition of wheat peptides to a culture medium significantly inhibited the indomethacin-induced release of malondialdehyde and nitrogen monoxide, and increased antioxidant enzyme activity in IEC-6 cells, thereby providing a possible explanation for the protective effect proposed for wheat peptides in the prevention of indomethacin-induced oxidative stress in small intestinal epithelial cells.

  16. Pre-cold stress increases acid stress resistance and induces amino ...

    African Journals Online (AJOL)

    Pre-cold stress increases acid stress resistance and induces amino acid homeostasis in Lactococcus lactis NZ9000. ... Purpose: To investigate the effects of pre-cold stress treatments on subsequent acid stress resistance ... from 32 Countries:.

  17. Nrf2 activation prevents cadmium-induced acute liver injury

    International Nuclear Information System (INIS)

    Wu, Kai C.; Liu, Jie J.; Klaassen, Curtis D.

    2012-01-01

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H 2 DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice were

  18. Nrf2 activation prevents cadmium-induced acute liver injury

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kai C. [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Liu, Jie J. [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States)

    2012-08-15

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H{sub 2}DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice

  19. Induced surface stress at crystal surfaces

    International Nuclear Information System (INIS)

    Dahmen, K.

    2002-05-01

    Changes of the surfaces stress Δτ (s) can be studied by observing the bending of thin crystalline plates. With this cantilever method one can gain the induced change of surface stress Δτ (s) from the bending of plates with the help of elasticity theory. For elastic isotropic substrates the relevant relations are known. Here the relations are generalized to elastic anisotropic crystals with a C 2v - Symmetry. The equilibrium shapes of crystalline plates oriented along the (100)-, (110)-, or (111)-direction which are clamped along one edge are calculated with a numeric method under the load of a homogeneous but pure isotropic or anisotropic surface stress. The results can be displayed with the dimensionality, so that the effect of clamping can be described in a systematic way. With these tabulated values one can evaluate cantilever experiments exactly. These results are generalized to cantilever methods for determining magnetoelastic constants. It is shown which magnetoelastic constants are measured in domains of thin films with ordered structures. The eigenshape and the eigenfrequency of plates constraint through a clamping at one side are calculated. These results give a deeper understanding of the elastic anisotropy. The induced surface stress of oxygen on the (110)-surface of molybdenum is measured along the principle directions Δτ [001] and Δτ [ anti 110] . The anisotropy of the surface stress is found for the p(2 x 2)-reconstruction. Lithium induces a tensile surface stress on the Molybdenum (110)-surface up to a coverage of Θ = 0, 3 monolayer. For a higher coverage the induced stress drops and reaches a level of less than -1, 2 N/m at one monolayer. It is shown, that cobalt induces a linear increasing stress with respect to the coverage on the (100)-surface of copper with a value of 2, 4GPa. The copper (100)-surface is bombarded with accelerated ions in the range between 800-2200 eV. The resulting induced compressive stress (Δτ (s) < 0) of the order

  20. Popular edible seaweed, Gelidium amansii prevents against diet-induced obesity.

    Science.gov (United States)

    Kang, Min-Cheol; Kang, Nalae; Kim, Seo-Young; Lima, Inês S; Ko, Seok-Chun; Kim, Young-Tae; Kim, Young-Bum; Jeung, Hee-Do; Choi, Kwang-Sik; Jeon, You-Jin

    2016-04-01

    The popular edible seaweed, Gelidium amansii is broadly used as food worldwide. To determine whether G. amansii extract (GAE) has protective effects on obesity, mice fed a high-fat diet (HFD) treated with GAE (1 and 3 %) were studied. After 12 weeks of GAE treatment, body weight was greatly decreased in mice fed a high-fat diet. This effect could be due to decreased adipogenesis, as evidenced by the fact that GAE suppressed adipogenic gene expression in adipocytes. In addition, blood glucose and serum insulin levels were reduced by GAE treatment in mice fed a high-fat diet, suggesting improvement in glucose metabolism. GAE supplementation also led to a significant decrease in total cholesterol and triglyceride levels. These data are further confirmed by H&E staining. Our findings indicate that Gelidium amansii prevents against the development of diet-induced obesity, and further implicate that GAE supplementation could be the therapeutical option for treatment of metabolic disorder such as obesity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Sirt3 confers protection against acrolein-induced oxidative stress in cochlear nucleus neurons.

    Science.gov (United States)

    Qu, Juan; Wu, Yong-Xiang; Zhang, Ting; Qiu, Yang; Ding, Zhong-Jia; Zha, Ding-Jun

    2018-03-01

    Acrolein is a ubiquitous dietary and environmental pollutant, which can also be generated endogenously during cellular stress. However, the molecular mechanisms underlying acrolein-induced neurotoxicity, especially in ototoxicity conditions, have not been fully determined. In this study, we investigated the mechanisms on acrolein-induced toxicity in primary cultured cochlear nucleus neurons with focus on Sirt3, a mitochondrial deacetylase. We found that acrolein treatment induced neuronal injury and programmed cell death (PCD) in a dose dependent manner in cochlear nucleus neurons, which was accompanied by increased intracellular reactive oxygen species (ROS) generation and lipid peroxidation. Acrolein exposure also significantly reduced the mitochondrial membrane potential (MMP) levels, promoted cytochrome c release and decreased mitochondrial ATP production. In addition, increased ER tracker fluorescence and activation of ER stress factors were observed after acrolein treatment, and the ER stress inhibitors were shown to attenuate acrolein-induced toxicity in cochlear nucleus neurons. The results of western blot and RT-PCR showed that acrolein markedly decreased the expression of Sirt3 at both mRNA and protein levels, and reduced the activity of downstream mitochondrial enzymes. Furthermore, overexpression of Sirt3 by lentivirus transfection partially prevented acrolein-induced neuronal injury in cochlear nucleus neurons. These results demonstrated that acrolein induces mitochondrial dysfunction and ER stress in cochlear nucleus neurons, and Sirt3 acts as an endogenous protective factor in acrolein-induced ototoxicity. Copyright © 2017. Published by Elsevier Ltd.

  2. Characterization of stress-induced suppression of long-term potentiation in the hippocampal CA1 field of freely moving rats.

    Science.gov (United States)

    Hirata, Riki; Togashi, Hiroko; Matsumoto, Machiko; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro

    2008-08-21

    Several lines of evidence have shown that exposure to stress impairs long-term potentiation (LTP) in the CA1 field of the hippocampus, but the detailed mechanisms for this effect remain to be clarified. The present study elucidated the synaptic mechanism of stress-induced LTP suppression in conscious, freely moving rats using electrophysiological approaches. Open field stress (i.e., novel environment stress) and elevated platform stress (i.e., uncontrollable stress) were employed. Basal synaptic transmission was significantly reduced during exposure to elevated platform stress but not during exposure to open field stress. LTP induction was blocked by elevated platform stress but not influenced by open field stress. Significant increases in serum corticosterone levels were observed in the elevated platform stress group compared with the open field stress group. Furthermore, LTP suppression induced by elevated platform stress was prevented by pretreatment with an anxiolytic drug diazepam (1 mg/kg, i.p.). These results suggest that stress-induced LTP suppression depends on the relative intensity of the stressor. The inhibitory synaptic response induced by an intense psychological stress, such as elevated platform stress, may be attributable to LTP impairment in the CA1 field of the hippocampus.

  3. Lycopene Protects against Hypoxia/Reoxygenation Injury by Alleviating ER Stress Induced Apoptosis in Neonatal Mouse Cardiomyocytes

    Science.gov (United States)

    Xu, Jiqian; Hu, Houxiang; Chen, Bin; Yue, Rongchuan; Zhou, Zhou; Liu, Yin; Zhang, Shuang; Xu, Lei; Wang, Huan; Yu, Zhengping

    2015-01-01

    Endoplasmic reticulum (ER) stress induced apoptosis plays a pivotal role in myocardial ischemia/reperfusion (I/R)-injury. Inhibiting ER stress is a major therapeutic target/strategy in treating cardiovascular diseases. Our previous studies revealed that lycopene exhibits great pharmacological potential in protecting against the I/R-injury in vitro and vivo, but whether attenuation of ER stress (and) or ER stress-induced apoptosis contributes to the effects remains unclear. In the present study, using neonatal mouse cardiomyocytes to establish an in vitro model of hypoxia/reoxygenation (H/R) to mimic myocardium I/R in vivo, we aimed to explore the hypothesis that lycopene could alleviate the ER stress and ER stress-induced apoptosis in H/R-injury. We observed that lycopene alleviated the H/R injury as revealed by improving cell viability and reducing apoptosis, suppressed reactive oxygen species (ROS) generation and improved the phosphorylated AMPK expression, attenuated ER stress as evidenced by decreasing the expression of GRP78, ATF6 mRNA, sXbp-1 mRNA, eIF2α mRNA and eIF2α phosphorylation, alleviated ER stress-induced apoptosis as manifested by reducing CHOP/GADD153 expression, the ratio of Bax/Bcl-2, caspase-12 and caspase-3 activity in H/R-treated cardiomyocytes. Thapsigargin (TG) is a potent ER stress inducer and used to elicit ER stress of cardiomyocytes. Our results showed that lycopene was able to prevent TG-induced ER stress as reflected by attenuating the protein expression of GRP78 and CHOP/GADD153 compared to TG group, significantly improve TG-caused a loss of cell viability and decrease apoptosis in TG-treated cardiomyocytes. These results suggest that the protective effects of lycopene on H/R-injury are, at least in part, through alleviating ER stress and ER stress-induced apoptosis in neonatal mouse cardiomyocytes. PMID:26291709

  4. Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Paola eGamba

    2015-06-01

    Full Text Available Alzheimer’s disease (AD, the most common neurodegenerative disorder associated with dementia, is typified by the pathological accumulation of amyloid β peptides and neurofibrillary tangles within the brain. Considerable evidence indicates that many events contribute to AD progression, including oxidative stress, inflammation, and altered cholesterol metabolism.The brain’s high lipid content makes it particularly vulnerable to oxidative species, with the consequent enhancement of lipid peroxidation and cholesterol oxidation, and the subsequent formation of end products, mainly 4-hydroxynonenal and oxysterols, respectively from the two processes. The chronic inflammatory events observed in the AD brain include activation of microglia and astrocytes, together with enhancement of inflammatory molecule and free radical release. Along with glial cells, neurons themselves have been found to contribute to neuroinflammation in the AD brain, by serving as sources of inflammatory mediators. Oxidative stress is intimately associated with neuroinflammation, and a vicious circle has been found to connect oxidative stress and inflammation in AD. Alongside oxidative stress and inflammation, altered cholesterol metabolism and hypercholesterolemia also significantly contribute to neuronal damage and to progression of AD. Increasing evidence is now consolidating the hypothesis that oxidized cholesterol is the driving force behind the development of AD, and that oxysterols are the link connecting the disease to altered cholesterol metabolism in the brain and hypercholesterolemia; this is because of the ability of oxysterols, unlike cholesterol, to cross the blood brain barrier. The key role of oxysterols in AD pathogenesis has been strongly supported by research pointing to their involvement in modulating neuroinflammation, Aβ accumulation, and cell death.This review highlights the key role played by cholesterol and oxysterols in the brain in AD pathogenesis.

  5. Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells.

    Science.gov (United States)

    Wang, Xin; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Luo, Jia

    2017-04-01

    Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Exposure to excess insulin (glargine) induces type 2 diabetes mellitus in mice fed on a chow diet.

    Science.gov (United States)

    Yang, Xuefeng; Mei, Shuang; Gu, Haihua; Guo, Huailan; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Cao, Wenhong

    2014-06-01

    We have previously shown that insulin plays an important role in the nutrient-induced insulin resistance. In this study, we tested the hypothesis that chronic exposure to excess long-acting insulin (glargine) can cause typical type 2 diabetes mellitus (T2DM) in normal mice fed on a chow diet. C57BL/6 mice were treated with glargine once a day for 8 weeks, followed by evaluations of food intake, body weight, blood levels of glucose, insulin, lipids, and cytokines, insulin signaling, histology of pancreas, ectopic fat accumulation, oxidative stress level, and cholesterol content in mitochondria in tissues. Cholesterol content in mitochondria and its association with oxidative stress in cultured hepatocytes and β-cells were also examined. Results show that chronic exposure to glargine caused insulin resistance, hyperinsulinemia, and relative insulin deficiency (T2DM). Treatment with excess glargine led to loss of pancreatic islets, ectopic fat accumulation in liver, oxidative stress in liver and pancreas, and increased cholesterol content in mitochondria of liver and pancreas. Prolonged exposure of cultured primary hepatocytes and HIT-TI5 β-cells to insulin induced oxidative stress in a cholesterol synthesis-dependent manner. Together, our results show that chronic exposure to excess insulin can induce typical T2DM in normal mice fed on a chow diet. © 2014 The authors.

  7. [Correction of lipid peroxidation and antioxidant system disorders by bioflavonoids during modeling of cholesterol atherosclerosis in rabbits].

    Science.gov (United States)

    Shysh, A M; Pashevin, D O; Dosenko, V Ie; Moĭbenko, O O

    2011-01-01

    We have studied the influence of bioflavonoids (quercetin, corvitin) on lipid peroxidation and antioxidant enzymes in the modeling of cholesterol atherosclerosis in rabbits. It has been shown that simultaneous administration of the quercetin derivative corvitin suppressed lipid peroxidation. We showed that under hypercholesterolemia, the concentration of malone dialdehyde in myocardial tissue in rabbits is significantly increased, while administration of bioflavonoids decreased the concentration of malone dialdehyde by 38.3%. Furthermore, corvitin caused activating effects on antioxidant enzymes superoxide dismutase and catalase in cardiac tissue. Our data suggest that bioflavonoids are able to suppress lipid peroxidation and prevent the decrease ofantioxidant enzymes activity in rabbits with cholesterol-rich diet induced atherosclerosis.

  8. Intracellular cholesterol level regulates sensitivity of glioblastoma cells against temozolomide-induced cell death by modulation of caspase-8 activation via death receptor 5-accumulation and activation in the plasma membrane lipid raft.

    Science.gov (United States)

    Yamamoto, Yutaro; Tomiyama, Arata; Sasaki, Nobuyoshi; Yamaguchi, Hideki; Shirakihara, Takuya; Nakashima, Katsuhiko; Kumagai, Kosuke; Takeuchi, Satoru; Toyooka, Terushige; Otani, Naoki; Wada, Kojiro; Narita, Yoshitaka; Ichimura, Koichi; Sakai, Ryuichi; Namba, Hiroki; Mori, Kentaro

    2018-01-01

    Development of resistance against temozolomide (TMZ) in glioblastoma (GBM) after continuous treatment with TMZ is one of the critical problems in clinical GBM therapy. Intracellular cholesterol regulates cancer cell biology, but whether intracellular cholesterol is involved in TMZ resistance of GBM cells remains unclear. The involvement of intracellular cholesterol in acquired resistance against TMZ in GBM cells was investigated. Intracellular cholesterol levels were measured in human U251 MG cells with acquired TMZ resistance (U251-R cells) and TMZ-sensitive control U251 MG cells (U251-Con cells), and found that the intracellular cholesterol level was significantly lower in U251-R cells than in U251-Con cells. In addition, treatment by intracellular cholesterol remover, methyl-beta cyclodextrin (MβCD), or intracellular cholesterol inducer, soluble cholesterol (Chol), regulated TMZ-induced U251-Con cell death in line with changes in intracellular cholesterol level. Involvement of death receptor 5 (DR5), a death receptor localized in the plasma membrane, was evaluated. TMZ without or with MβCD and/or Chol caused accumulation of DR5 into the plasma membrane lipid raft and formed a complex with caspase-8, an extrinsic caspase cascade inducer, reflected in the induction of cell death. In addition, treatment with caspase-8 inhibitor or knockdown of DR5 dramatically suppressed U251-Con cell death induced by combination treatment with TMZ, MβCD, and Chol. Combined treatment of Chol with TMZ reversed the TMZ resistance of U251-R cells and another GBM cell model with acquired TMZ resistance, whereas clinical antihypercholesterolemia agents at physiological concentrations suppressed TMZ-induced cell death of U251-Con cells. These findings suggest that intracellular cholesterol level affects TMZ treatment of GBM mediated via a DR5-caspase-8 mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats

    Directory of Open Access Journals (Sweden)

    Ebaid Hossam

    2013-02-01

    Full Text Available Abstract This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1, interferon gamma (IFN-γ, programmed cell death-receptor (Fas and Tumor necrosis factor-alpha (TNF-α mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA, cholesterol, LDL, triglycerides, bilirubin and urea. In addition, CCl4 was found to significantly suppress the activity of both catalase and glutathione (GSH and decrease the levels of serum total protein and HDL-cholesterol. All of these parameters were restored to their normal levels by treatment with melatonin, folic acid or their combination. An improvement of the general hepatic architecture was observed in rats that were treated with the combination of melatonin and folic acid along with CCl4. Furthermore, the CCl4-induced upregulation of TNF-α and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-γ and Akt1 mRNA expression. The combination of melatonin and folic acid exhibited ability to reduce the markers of liver injury induced by CCl4 and restore the oxidative stability, the level of inflammatory cytokines, the lipid profile and the cell survival Akt1 signals.

  10. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.

    Science.gov (United States)

    Vogel, Susanne; Klumpers, Floris; Schröder, Tobias Navarro; Oplaat, Krista T; Krugers, Harm J; Oitzl, Melly S; Joëls, Marian; Doeller, Christian F; Fernández, Guillén

    2017-05-01

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.

  11. Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats

    Directory of Open Access Journals (Sweden)

    Thewarid Berkban

    2015-06-01

    Full Text Available The effect of ellagic acid on oxidative stress and hypertension induced by Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day for five weeks. L-NAME induced high systolic blood pressure (SBP and increased heart rate (HR, hindlimb vascular resistance (HVR and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability.

  12. Quercetin prevents pyrrolizidine alkaloid clivorine-induced liver injury in mice by elevating body defense capacity.

    Directory of Open Access Journals (Sweden)

    Lili Ji

    Full Text Available Quercetin is a plant-derived flavonoid that is widely distributed in nature. The present study is designed to analyze the underlying mechanism in the protection of quercetin against pyrrolizidine alkaloid clivorine-induced acute liver injury in vivo. Serum transaminases, total bilirubin analysis, and liver histological evaluation demonstrated the protection of quercetin against clivorine-induced liver injury. Terminal dUTP nick end-labeling assay demonstrated that quercetin reduced the increased amount of liver apoptotic cells induced by clivorine. Western-blot analysis of caspase-3 showed that quercetin inhibited the cleaved activation of caspase-3 induced by clivorine. Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine. Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine. Results of the Mouse Stress and Toxicity PathwayFinder RT2 Profiler PCR Array demonstrated that the expression of genes related with oxidative or metabolic stress and heat shock was obviously altered after quercetin treatment. Some of the alterations were confirmed by real-time PCR. Our results demonstrated that quercetin prevents clivorine-induced acute liver injury in vivo by inhibiting apoptotic cell death and ameliorating oxidative stress injury. This protection may be caused by the elevation of the body defense capacity induced by quercetin.

  13. Quercetin Prevents Pyrrolizidine Alkaloid Clivorine-Induced Liver Injury in Mice by Elevating Body Defense Capacity

    Science.gov (United States)

    Ji, Lili; Ma, Yibo; Wang, Zaiyong; Cai, Zhunxiu; Pang, Chun; Wang, Zhengtao

    2014-01-01

    Quercetin is a plant-derived flavonoid that is widely distributed in nature. The present study is designed to analyze the underlying mechanism in the protection of quercetin against pyrrolizidine alkaloid clivorine-induced acute liver injury in vivo. Serum transaminases, total bilirubin analysis, and liver histological evaluation demonstrated the protection of quercetin against clivorine-induced liver injury. Terminal dUTP nick end-labeling assay demonstrated that quercetin reduced the increased amount of liver apoptotic cells induced by clivorine. Western-blot analysis of caspase-3 showed that quercetin inhibited the cleaved activation of caspase-3 induced by clivorine. Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine. Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine. Results of the Mouse Stress and Toxicity PathwayFinder RT2 Profiler PCR Array demonstrated that the expression of genes related with oxidative or metabolic stress and heat shock was obviously altered after quercetin treatment. Some of the alterations were confirmed by real-time PCR. Our results demonstrated that quercetin prevents clivorine-induced acute liver injury in vivo by inhibiting apoptotic cell death and ameliorating oxidative stress injury. This protection may be caused by the elevation of the body defense capacity induced by quercetin. PMID:24905073

  14. Inhibition of serum cholesterol oxidation by dietary vitamin C and selenium intake in high fat fed rats.

    Science.gov (United States)

    Menéndez-Carreño, M; Ansorena, D; Milagro, F I; Campión, J; Martínez, J A; Astiasarán, I

    2008-04-01

    Cholesterol oxidation products (COPs) have been considered as specific in vivo markers of oxidative stress. In this study, an increased oxidative status was induced in Wistar rats by feeding them a high-fat diet (cafeteria diet). Another group of animals received the same diet supplemented with a combination of two different antioxidants, ascorbic acid (100 mg/kg rat/day) and sodium selenite (200 microg/kg rat/day) and a third group fed on a control diet. Total and individual COPs analysis of the different diets showed no differences among them. At the end of the experimental trial, rats were sacrificed and serum cholesterol, triglycerides and COPs were measured. None of the diets induced changes in rats body weight, total cholesterol and triglycerides levels. Serum total COPs in rats fed on the high-fat diet were 1.01 microg/ml, two times the amount of the control rats (0.47 microg/ml). When dietary antioxidant supplementation was given, serum total COPs concentration (0.44 microg/ml) showed the same levels than those of the rats on control diet. 7beta-hydroxycholesterol, formed non-enzymatically via cholesterol peroxidation in the presence of reactive oxygen species, showed slightly lower values in the antioxidant-supplemented animals compared to the control ones. This study confirms the importance of dietary antioxidants as protective factors against the formation of oxysterols.

  15. Low-Intensity Pulsed Ultrasound Prevents the Oxidative Stress Induced Endothelial-Mesenchymal Transition in Human Aortic Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Jiamin Li

    2018-02-01

    Full Text Available Background/Aims: Endothelial-mesenchymal transition (EndMT has been shown to take part in the generation and progression of diverse diseases, involving a series of changes leading to a loss of their endothelial characteristics and an acquirement of properties typical of mesenchymal cells. Low-intensity pulsed ultrasound (LIPUS is a new therapeutic option that has been successfully used in fracture healing. However, whether LIPUS can inhibit oxidative stress-induced endothelial cell damages through inhibiting EndMT remained unknown. This study aimed to investigate the protective effects of LIPUS against oxidative stress-induced endothelial cell damages and the underlying mechanisms. Methods: EndMT was induced by H2O2 (100 µm for seven days. Human aortic endothelial cells (HAECs were exposed to H2O2 with or without LIPUS treatment for seven days. The expression of EndMT markers (CD31, VE-cadherin, FSP1 and α-SMA were analyzed. The levels of total and phosphorylated PI3K and AKT proteins were detected by Western Blot analysis. Cell chemotaxis was determined by wound healing and transwell assay. Results: LIPUS relieved EndMT by decreasing ROS accumulation and increasing activation of the PI3K signaling cascade. LIPUS alleviated the migration of EndMT-derived mesenchymal-like cells through reducing extracellular matrix (ECM deposition that is associated with matrix metallopeptidase (MMP proteolytic activity and collagen production. Conclusion: LIPUS produces cytoprotective effects against oxidative injuries to endothelial cells through suppressing the oxidative stress-induced EndMT, activating the PI3K/AKT pathway under oxidative stress, and limiting cell migration and excessive ECM deposition.

  16. Cholesterol Check (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2015-09-10

    Heart disease and stroke are among the leading causes of death in the U.S. One of the main risk factors is high blood cholesterol. In this podcast, Dr. Carla Mercado discusses the importance of a healthy diet and regular screening to prevent high blood cholesterol.  Created: 9/10/2015 by MMWR.   Date Released: 9/10/2015.

  17. Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands

    OpenAIRE

    Kna?, M.; Maciejczyk, M.; Daniszewska, I.; Klimiuk, A.; Matczuk, J.; Ko?odziej, U.; Waszkiel, D.; ?adny, J. R.; ?endzian-Piotrowska, M.; Zalewska, A.

    2016-01-01

    Objective. This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM). Materials and Methods. Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2′-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal protein adduct (4-HNE), oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA), 8-isoprostanes (8-isoP), and oxidative stress index (OSI) were measured at 7 (groups 1 and 3) and 14...

  18. FLIM studies of 22- and 25-NBD-cholesterol in living HEK293 cells: Plasma membrane change induced by cholesterol depletion

    Czech Academy of Sciences Publication Activity Database

    Ostašov, Pavel; Sýkora, Jan; Brejchová, Jana; Olžyńska, Agnieszka; Hof, Martin; Svoboda, Petr

    167-168, FEB-MAR (2013), s. 62-69 ISSN 0009-3084 R&D Projects: GA ČR(CZ) GAP207/12/0919 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 ; RVO:61388955 Keywords : cholesterol depletion * beta-Cyclodextrin * 22-NBD-cholesterol * 25-NBD-cholesterol * FLIM studies * intact HEK293 cells Subject RIV: CE - Biochemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 2.593, year: 2013

  19. Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

    Science.gov (United States)

    Koizumi, So; Onozuka, Minoru

    2015-01-01

    The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior. PMID:26075223

  20. Chewing prevents stress-induced hippocampal LTD formation and anxiety-related behaviors: a possible role of the dopaminergic system.

    Science.gov (United States)

    Ono, Yumie; Koizumi, So; Onozuka, Minoru

    2015-01-01

    The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior.

  1. Inhibitory effects of myricitrin on oxidative stress-induced endothelial damage and early atherosclerosis in ApoE −/− mice

    International Nuclear Information System (INIS)

    Sun, Gui-bo; Qin, Meng; Ye, Jing-xue; Pan, Rui-le; Meng, Xiang-bao; Wang, Min; Luo, Yun; Li, Zong-yang; Wang, Hong-wei; Sun, Xiao-bo

    2013-01-01

    Atherosclerosis (AS) is a state of heightened oxidative stress characterized by lipid and protein oxidation in vascular walls. Oxidative stress-induced vascular endothelial cell (VEC) injury is a major factor in the pathogenesis of AS. Myricitrin, a natural flavonoid isolated from the root bark of Myrica cerifera, was recently found to have a strong antioxidative effect. However, its use for treating cardiovascular diseases, especially AS is still unreported. Consequently, we evaluated the cytoprotective effect of myricitrin on AS by assessing oxidative stress-induced VEC damage. The in vivo study using an ApoE −/− mouse model of AS demonstrated that myricitrin treatment protects against VEC damage and inhibits early AS plaque formation. This effect is associated with the antioxidative effect of myricitrin, as observed in a hydrogen peroxide (H 2 O 2 )-induced rat model of artery endothelial injury and primary cultured human VECs. Myricitrin treatment also prevents and attenuates H 2 O 2 -induced endothelial injury. Further investigation of the cytoprotective effects of myricitrin demonstrated that myricitrin exerts its function by scavenging for reactive oxygen species, as well as reducing lipid peroxidation, blocking NO release, and maintaining mitochondrial transmembrane potential. Myricitrin treatment also significantly decreased H 2 O 2 -induced apoptosis in VECs, which was associated with significant inhibition of p53 gene expression, activation of caspase-3 and the MAPK signaling pathway, and alteration of the patterns of pro-apoptotic and anti-apoptotic gene expression. The resulting significantly increased bcl-2/bax ratio indicates that myricitrin may prevent the apoptosis induced by oxidative stress injury. - Highlights: • Myricitrin prevents early atherosclerosis in ApoE−/− mice. • Myricitrin protects endothelial cell from H 2 O 2 induced injury in rat and HUVECs. • Myricitrin enhanced NO release and up regulates eNOS activity in HUVECs.

  2. Stress-induced eating in women with binge-eating disorder and obesity.

    Science.gov (United States)

    Klatzkin, Rebecca R; Gaffney, Sierra; Cyrus, Kathryn; Bigus, Elizabeth; Brownley, Kimberly A

    2018-01-01

    measuring the motivational versus hedonic aspects of stress-induced eating may expose nuanced eating behaviors that differentiate BED and obesity. If confirmed, our findings would support prevention and treatment strategies that target subsets of women based on obesity and BED status. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats.

    Science.gov (United States)

    Javadi, Parastoo; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

    2017-07-01

    The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5-4 µg/rat) or intra-medial prefrontal cortex (0.2-0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.

  4. Anesthetic-Induced Oxidative Stress and Potential Protection

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    2010-01-01

    Full Text Available Prolonged exposure of developing mammals to general anesthetics affects the N-methyl-D-aspartate (NMDA–type glutamate or γ-aminobutyric acid (GABA receptor systems and enhances neuronal toxicity. Stimulation of immature neurons by NMDA antagonists or GABA agonists is thought to increase overall nervous system excitability and may contribute to abnormal neuronal cell death during development. Although the precise mechanisms by which NMDA antagonists or GABA agonists cause neuronal cell death are still not completely understood, up-regulation of the NMDA receptor subunit NR1 may be an initiative factor in neuronal cell death. It is increasingly apparent that mitochondria lie at the center of the cell death regulation process. Evidence for the role of oxidative stress in anesthetic-induced neurotoxicity has been generated in studies that apply oxidative stress blockers. Prevention of neuronal death by catalase and superoxide dismutase in vitro, or by M40403 (superoxide dismutase mimetic in vivo, supports the contention that the involvement of reactive oxygen species (ROS and the nature of neuronal cell death in rodents is mainly apoptotic. However, more evidence is necessary to in order verify the role of the NMDA receptor subunit NR1 and ROS in anesthetic-induced neurodegeneration.

  5. [Stress-induced cellular adaptive mutagenesis].

    Science.gov (United States)

    Zhu, Linjiang; Li, Qi

    2014-04-01

    The adaptive mutations exist widely in the evolution of cells, such as antibiotic resistance mutations of pathogenic bacteria, adaptive evolution of industrial strains, and cancerization of human somatic cells. However, how these adaptive mutations are generated is still controversial. Based on the mutational analysis models under the nonlethal selection conditions, stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint. The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses, including DNA damages caused by accumulation of intracellular toxic chemicals, limitation of DNA MMR (mismatch repair) activity, upregulation of general stress response and activation of SOS response. These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one. The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity. In addition, gene transcription under stress condition increases the instability of genome in response to DNA damage, resulting in transcription-associated DNA mutagenesis. In this review, we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

  6. Inhibitory Effects of Simvastatin on Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Vascular Endothelial Cells.

    Science.gov (United States)

    Zhang, Guo-Qiang; Tao, Yong-Kang; Bai, Yong-Ping; Yan, Sheng-Tao; Zhao, Shui-Ping

    2018-04-20

    Oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress and endothelial apoptosis are essential for atherosclerosis. Our previous study has shown that ox-LDL-induced apoptosis is mediated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α-subunit (eIF2α)/CCAAT/enhancer-binding protein homologous protein (CHOP) endoplasmic reticulum (ER) stress pathway in endothelial cells. Statins are cholesterol-lowering drugs that exert pleiotropic effects including suppression of oxidative stress. This study aimed to explore the roles of simvastatin on ox-LDL-induced ER stress and apoptosis in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were treated with simvastatin (0.1, 0.5, or 2.5 μmol/L) or DEVD-CHO (selective inhibitor of caspase-3, 100 μmol/L) for 1 h before the addition of ox-LDL (100 μg/ml) and then incubated for 24 h, and untreated cells were used as a control group. Apoptosis, expression of PERK, phosphorylation of eIF2α, CHOP mRNA level, and caspase-3 activity were measured. Comparisons among multiple groups were performed with one-way analysis of variance (ANOVA) followed by post hoc pairwise comparisons using Tukey's tests. A value of P LDL resulted in a significant increase in apoptosis (31.9% vs. 4.9%, P LDL-induced apoptosis (28.0%, 24.7%, and 13.8%, F = 15.039, all P LDL significantly increased the expression of PERK (499.5%, P LDL-induced expression of PERK (407.8%, 339.1%, and 187.5%, F = 10.121, all P LDL-induced expression of PERK (486.4%) and phosphorylation of eIF2α (418.8%). Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment. This study suggested that simvastatin could inhibit ox-LDL-induced ER stress and apoptosis in vascular endothelial cells.

  7. Modelling of the Hypothalamic-Pituitary-Adrenal Axis Perturbations by Externally Induced Cholesterol Pulses of Finite Duration and with Asymmetrically Distributed Concentration Profile

    Science.gov (United States)

    Stanojević, A.; Marković, V. M.; Čupić, Ž.; Vukojević, V.; Kolar-Anić, L.

    2017-12-01

    A model was developed that can be used to study the effect of gradual cholesterol intake by food on the HPA axis dynamics. Namely, well defined oscillatory dynamics of vital neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis has proven to be necessary for maintaining regular basal physiology and formulating appropriate stress response to various types of perturbations. Cholesterol, as a precursor of all steroid HPA axis hormones, can alter the dynamics of HPA axis. To analyse its particular influence on the HPA axis dynamics we used stoichiometric model of HPA axis activity, and simulate cholesterol perturbations in the form of finite duration pulses, with asymmetrically distributed concentration profile. Our numerical simulations showed that there is a complex, nonlinear dependence between the HPA axis responsiveness and different forms of applied cholesterol concentration pulses, indicating the significance of kinetic modelling, and dynamical systems theory for the understanding of large-scale self-regulatory, and homeostatic processes within this neuroendocrine system.

  8. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway.

    Science.gov (United States)

    Xu, Xiaolin; Li, Qian; Pang, Liewen; Huang, Guoqian; Huang, Jiechun; Shi, Meng; Sun, Xiaotian; Wang, Yiqing

    2013-11-15

    Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Antioxidant Activity of Cabbage and/or Carrot Against Oxidative Stress Induced by Gamma Irradiation in Male Albino Rats

    International Nuclear Information System (INIS)

    Hamza, R.G.; Mahmoud, K.A.

    2011-01-01

    Several studies indicated that diets rich in fruits and vegetables are protective against diseases, and populations that consume such diets have higher plasma antioxidants and exhibit lower risk of cancer and cardiovascular diseases. Vegetable is considered major dietary source of fibers and antioxidants such as polyphenols, flavonoids and carotenoids that can protect against different dietary disorders. The present study was carried out to investigate the potential protective effects of cabbage and/or carrot against oxidative stress induced by gamma irradiation in male albino rats. Chemical composition and phenolic contents in cabbage and carrot were determined. Male albino rats were exposed to 5 Gy (single dose with rate 0.46 Gy/min) of whole body gamma irradiation. Thirty five rats were randomly divided into five groups as follow: group 1: control (rats fed on balanced diet for 6 weeks), group 2: irradiated (rats were exposed to whole gamma irradiation and fed on balanced diet for 6 weeks) and groups 3, 4 and 5: irradiated rats fed on balanced diet and received cabbage 15%, carrot 15% and a combination of cabbage and carrot, respectively. The results obtained revealed that the administration of cabbage and/or carrot diet significantly reduced the changes induced by gamma irradiation in the serum level of glucose and liver function parameters; serum aminotransferases (AST, ALT), alkaline phosphatase (ALP), total protein and albumin. In addition, significant improvements were observed in the serum levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C). Significant enhancement in hepatic antioxidant enzymes; superoxide dismutase (SOD) and catalase (CAT), was observed. The levels of reduced glutathione (GSH) associated with remarkable decrease in the level of lipid peroxidation (TBARS) were observed. Accordingly, it could be concluded that consumption of cabbage and/or carrot

  10. Swimming training induces liver adaptations to oxidative stress and insulin sensitivity in rats submitted to high-fat diet.

    Science.gov (United States)

    Zacarias, Aline Cruz; Barbosa, Maria Andrea; Guerra-Sá, Renata; De Castro, Uberdan Guilherme Mendes; Bezerra, Frank Silva; de Lima, Wanderson Geraldo; Cardoso, Leonardo M; Santos, Robson Augusto Souza Dos; Campagnole-Santos, Maria José; Alzamora, Andréia Carvalho

    2017-11-01

    Oxidative stress, physical inactivity and high-fat (FAT) diets are associated with hepatic disorders such as metabolic syndrome (MS). The therapeutic effects of physical training (PT) were evaluated in rats with MS induced by FAT diet for 13 weeks, on oxidative stress and insulin signaling in the liver, during the last 6 weeks. FAT-sedentary (SED) rats increased body mass, retroperitoneal fat, mean arterial pressure (MAP) and heart rate (HR), and total cholesterol, serum alanine aminotransferase, glucose and insulin. Livers of FAT-SED rats increased superoxide dismutase activity, thiobarbituric acid-reactive substances, protein carbonyl and oxidized glutathione (GSSG); and decreased catalase activity, reduced glutathione/GSSG ratio, and the mRNA expression of insulin receptor substrate 1 (IRS-1) and serine/threonine kinase 2. FAT-PT rats improved in fitness and reduced their body mass, retroperitoneal fat, and glucose, insulin, total cholesterol, MAP and HR; and their livers increased superoxide dismutase and catalase activities, the reduced glutathione/GSSG ratio and the expression of peroxisome proliferator-activated receptor gamma and insulin receptor compared to FAT-SED rats. These findings indicated adaptive responses to PT by restoring the oxidative balance and insulin signaling in the liver and certain biometric and biochemical parameters as well as MAP in MS rats.

  11. Gly[14]-humanin inhibits ox-LDL uptake and stimulates cholesterol efflux in macrophage-derived foam cells.

    Science.gov (United States)

    Zhu, Wa-Wa; Wang, Shu-Rong; Liu, Zhi-Hua; Cao, Yong-Jun; Wang, Fen; Wang, Jing; Liu, Chun-Feng; Xie, Ying; Xie, Ying; Zhang, Yan-Lin

    2017-01-01

    Foam cell formation, which is caused by imbalanced cholesterol influx and efflux by macrophages, plays a vital role in the occurrence and development of atherosclerosis. Humanin (HN), a mitochondria-derived peptide, can prevent the production of reactive oxygen species and death of human aortic endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL) and has a protective effect on patients with in early atherosclerosis. However, the effects of HN on the regulation of cholesterol metabolism in RAW 264.7 macrophages are still unknown. This study was designed to investigate the role of [Gly14]-humanin (HNG) in lipid uptake and cholesterol efflux in RAW 264.7 macrophages. Flow cytometry and live cell imaging results showed that HNG reduced Dil-ox-LDL accumulation in the RAW 264.7 macrophages. A similar result was obtained for lipid accumulation by measuring cellular cholesterol content. Western blot analysis showed that ox-LDL treatment upregulated not only the protein expression of CD36 and LOX-1, which mediate ox-LDL endocytosis, but also ATP-binding cassette (ABC) transporter A1 and ABCG1, which mediate ox-LDL exflux. HNG pretreatment inhibited the upregulation of CD36 and LOX-1 levels, prompting the upregulation of ABCA1 and ABCG1 levels induced by ox-LDL. Therefore we concluded that HNG could inhibit ox-LDL-induced macrophage-derived foam cell formation, which occurs because of a decrease in lipid uptake and an increase in cholesterol efflux from macrophage cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Intranasal cotinine improves memory, and reduces depressive-like behavior, and GFAP+ cells loss induced by restraint stress in mice.

    Science.gov (United States)

    Perez-Urrutia, Nelson; Mendoza, Cristhian; Alvarez-Ricartes, Nathalie; Oliveros-Matus, Patricia; Echeverria, Florencia; Grizzell, J Alex; Barreto, George E; Iarkov, Alexandre; Echeverria, Valentina

    2017-09-01

    Posttraumatic stress disorder (PTSD), chronic psychological stress, and major depressive disorder have been found to be associated with a significant decrease in glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus of rodents. Cotinine is an alkaloid that prevents memory impairment, depressive-like behavior and synaptic loss when co-administered during restraint stress, a model of PTSD and stress-induced depression, in mice. Here, we investigated the effects of post-treatment with intranasal cotinine on depressive- and anxiety-like behaviors, visual recognition memory as well as the number and morphology of GFAP+ immunoreactive cells, in the hippocampus and frontal cortex of mice subjected to prolonged restraint stress. The results revealed that in addition to the mood and cognitive impairments, restraint stress induced a significant decrease in the number and arborization of GFAP+ cells in the brain of mice. Intranasal cotinine prevented these stress-derived symptoms and the morphological abnormalities GFAP+ cells in both of these brain regions which are critical to resilience to stress. The significance of these findings for the therapy of PTSD and depression is discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Role of Nrf2 in preventing oxidative stress induced chloride current alteration in human lung cells.

    Science.gov (United States)

    Canella, Rita; Benedusi, Mascia; Martini, Marta; Cervellati, Franco; Cavicchio, Carlotta; Valacchi, Giuseppe

    2018-08-01

    The lung tissue is one of the main targets of oxidative stress due to external sources and respiratory activity. In our previous work, we have demonstrated in that O 3 exposure alters the Cl - current-voltage relationship, with the appearance of a large outward rectifier component mainly sustained by outward rectifier chloride channels (ORCCs) in human lung epithelial cells (A549 line). In the present study, we have performed patch clamp experiments, in order to identify which one of the O 3 byproducts (4hydroxynonenal (HNE) and/or H 2 O 2 ) was responsible for chloride current change. While 4HNE exposition (up to 25 μM for 30' before electrophysiological analysis) did not reproduce O 3 effect, H 2 O 2 produced by glucose oxidase 10 mU for 24 hr before electrophysiological analysis mimicked O 3 response. This result was confirmed treating the cell with catalase (CAT) before O 3 exposure (1,000 U/ml for 2 hr): CAT was able to rescue Cl - current alteration. Since CAT is regulated by Nrf2 transcription factor, we pre-treated the cells with the Nrf2 activators, resveratrol and tBHQ. Immunochemical and immunocytochemical results showed Nrf2 activation with both substances that lead to prevent OS effect on Cl - current. These data bring new insights into the mechanisms involved in OS-induced lung tissue damage, pointing out the role of H 2 O 2 in chloride current alteration and the ability of Nfr2 activation in preventing this effect. © 2017 Wiley Periodicals, Inc.

  14. Repeated Predictable Stress Causes Resilience against Colitis-Induced Behavioral Changes in Mice

    Directory of Open Access Journals (Sweden)

    Ahmed M Hassan

    2014-11-01

    Full Text Available Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2 % in drinking water decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and social interaction tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY, a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis.

  15. Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

    Science.gov (United States)

    Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

    2013-11-15

    Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

  16. Resveratrol protects rabbits against cholesterol diet- induced ...

    African Journals Online (AJOL)

    ... groups compared to HFD group only. In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrations and might be beneficial in treatment of hyperlipidemia and atherosclerosis. Keywords: Cholesterol diet, Lipidaemia, Rabbit; Resveratrol, LDL-c, HDL-c, TC, TG ...

  17. Increased cholinergic contractions of jejunal smooth muscle caused by a high cholesterol diet are prevented by the 5-HT4 agonist – tegaserod

    Directory of Open Access Journals (Sweden)

    Shaffer Eldon

    2006-02-01

    Full Text Available Abstract Background Excess cholesterol in bile and in blood is a major risk factor for the respective development of gallbladder disease and atherosclerosis. This lipid in excess negatively impacts the functioning of other smooth muscles, including the intestine. Serotonin is an important mediator of the contractile responses of the small intestine. Drugs targeting the serotonin receptor are used as prokinetic agents to manage intestinal motor disorders, in particular irritable bowel syndrome. Thus, tegaserod, acting on 5-HT4 receptor, ideally should obviate detrimental effects of excessive cholesterol on gastrointestinal smooth muscle. In this study we examined the effect of tegaserod on cholesterol-induced changes in the contractile responses of intestinal smooth muscle. Methods The effects of a high cholesterol (1% diet on the in vitro contractile responses of jejunal longitudinal smooth muscle from Richardson ground squirrels to the cholinergic agonist carbachol were examined in the presence or absence of tetrodrodotoxin (TTX. Two groups of animals, fed either low (0.03% or high cholesterol rat chow diet, were further divided into two subgroups and treated for 28 days with either vehicle or tegaserod. Results The high cholesterol diet increased, by nearly 2-fold, contractions of the jejunal longitudinal smooth muscle elicited by carbachol. These cholinergic contractions were mediated by muscarinic receptors since they were blocked by scopolamine, a muscarinic receptor antagonist, but not by the nicotinic receptor antagonist, hexamethonium. Tegaserod treatment, which did not affect cholinergic contractions of tissues from low cholesterol fed animals, abrogated the increase caused by the high cholesterol diet. With low cholesterol diet TTX enhanced carbachol-evoked contractions, whereas this action potential blocker did not affect the augmented cholinergic contractions seen with tissues from animals on the high cholesterol diet. Tegaserod

  18. Cholesterol Protects the Oxidized Lipid Bilayer from Water Injury

    DEFF Research Database (Denmark)

    Owen, Michael C; Kulig, Waldemar; Rog, Tomasz

    2018-01-01

    In an effort to delineate how cholesterol protects membrane structure under oxidative stress conditions, we monitored the changes to the structure of lipid bilayers comprising 30 mol% cholesterol and an increasing concentration of Class B oxidized 1-palmitoyl-2-oleoylphosphatidylcholine (POPC...... in a characteristic reduction in bilayer thickness and increase in area per lipid, thereby increasing the exposure of the membrane hydrophobic region to water. However, cholesterol was observed to help reduce water injury by moving into the bilayer core and forming more hydrogen bonds with the oxPLs. Cholesterol also...... resists altering its tilt angle, helping to maintain membrane integrity. Water that enters the 1-nm-thick core region remains part of the bulk water on either side of the bilayer, with relatively few water molecules able to traverse through the bilayer. In cholesterol-rich membranes, the bilayer does...

  19. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    Directory of Open Access Journals (Sweden)

    Matthias Orth

    2012-01-01

    Full Text Available Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules. We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

  20. Hepatoprotective effects of fermented Curcuma longa L. on carbon tetrachloride-induced oxidative stress in rats.

    Science.gov (United States)

    Kim, Yongjae; You, Yanghee; Yoon, Ho-Geun; Lee, Yoo-Hyun; Kim, Kyungmi; Lee, Jeongmin; Kim, Min Soo; Kim, Jong-Choon; Jun, Woojin

    2014-05-15

    The hepatoprotective effect of fermented Curcuma longa L. (FC) was investigated in rats under CCl4-induced oxidative stress. FC at a dose of 30 or 300 mg/kg body weight (b.w.) was orally administered for 14 days followed by a single dose of CCl4 (1.25 mL/kg b.w. in 20% corn oil) on day 14. Pretreatment with FC drastically prevented the elevated activities of serum AST, ALT, LDH, and ALP caused by CCl4-induced hepatotoxicity. Histopathologically evident hepatic necrosis was significantly ameliorated by FC pretreatment. When compared to the CCl4-alone treated group, rats pretreated with FC displayed the reduced level of malondialdehyde. Furthermore, FC enhanced antioxidant capacities with higher activities of catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase, and level of reduced glutathione. These results suggest that FC could be a candidate used for the prevention against various liver diseases induced by oxidative stress via elevating antioxidative potentials and decreasing lipid peroxidation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

    Directory of Open Access Journals (Sweden)

    Yumie Ono

    2015-01-01

    Full Text Available The present study examined the effects of chewing on stress-induced long-term depression (LTD and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior.

  2. Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis

    Directory of Open Access Journals (Sweden)

    Maria Razzoli

    2016-01-01

    Conclusion: Our findings demonstrate that thermogenesis and BAT function are determinant of the resilience or vulnerability to stress-induced obesity. Our data support a model in which adrenergic and purinergic pathways exert complementary/synergistic functions in BAT, thus suggesting an alternative to βARs agonists for the activation of human BAT.

  3. Polyphenol-Rich Blackcurrant Juice Prevents Endothelial Dysfunction in the Mesenteric Artery of Cirrhotic Rats with Portal Hypertension: Role of Oxidative Stress and the Angiotensin System.

    Science.gov (United States)

    Rashid, Sherzad; Idris-Khodja, Noureddine; Auger, Cyril; Kevers, Claire; Pincemail, Joël; Alhosin, Mahmoud; Boehm, Nelly; Oswald-Mammosser, Monique; Schini-Kerth, Valérie B

    2018-04-01

    Chronic liver diseases with portal hypertension are characterized by a progressive vasodilatation, endothelial dysfunction, and NADPH oxidase-derived vascular oxidative stress, which have been suggested to involve the angiotensin system. This study evaluated the possibility that oral intake of polyphenol-rich blackcurrant juice (PRBJ), a rich natural source of antioxidants, prevents endothelial dysfunction in a rat model of cirrhosis induced by chronic bile duct ligation (CBDL), and, if so, determined the underlying mechanism. Male Wistar rats received either control drinking water or water containing 60 mg/kg gallic acid equivalents of PRBJ for 3 weeks before undergoing surgery with CBDL or sham surgery. After 4 weeks, vascular reactivity was assessed in mesenteric artery rings using organ chambers. Both the acetylcholine-induced nitric oxide (NO)- and endothelium-dependent hyperpolarization (EDH)-mediated relaxations in mesenteric artery rings were significantly reduced in CBDL rats compared to sham rats. An increased level of oxidative stress and expression of NADPH oxidase subunits, COX-2, NOS, and of the vascular angiotensin system are observed in arterial sections in the CBDL group. Chronic intake of PRBJ prevented the CBDL-induced impaired EDH-mediated relaxation, oxidative stress, and expression of the different target proteins in the arterial wall. In addition, PRBJ prevented the CBDL-induced increase in the plasma level of proinflammatory cytokines (interleukin [IL]-1α, monocyte chemotactic protein 1, and tumor necrosis factor α) and the decrease of the anti-inflammatory cytokine, IL-4. Altogether, these observations indicate that regular ingestion of PRBJ prevents the CBDL-induced endothelial dysfunction in the mesenteric artery most likely by normalizing the level of vascular oxidative stress and the angiotensin system.

  4. Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.

    Science.gov (United States)

    Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

    2012-11-01

    The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

  5. N-acetylcysteine protects against cadmium-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in testes.

    Science.gov (United States)

    Ji, Yan-Li; Wang, Hua; Zhang, Cheng; Zhang, Ying; Zhao, Mei; Chen, Yuan-Hua; Xu, De-Xiang

    2013-03-01

    Cadmium (Cd) is a reproductive toxicant that induces germ cell apoptosis in the testes. Previous studies have demonstrated that endoplasmic reticulum (ER) stress is involved in Cd-induced germ cell apoptosis. The aim of the present study was to investigate the effects of N-acetylcysteine (NAC), an antioxidant, on Cd-induced ER stress and germ cell apoptosis in the testes. Male CD-1 mice were intraperitoneally injected with CdCl2 (2.0 mg kg(-1)). As expected, acute Cd exposure induced germ cell apoptosis in the testes, as determined by terminal dUTP nick-end labelling (TUNEL). However, the administration of NAC alleviated Cd-induced germ cell apoptosis in the testes. Further analysis showed that NAC attenuated the Cd-induced upregulation of testicular glucose-regulated protein 78 (GRP78), an important ER molecular chaperone. Moreover, NAC inhibited the Cd-induced phosphorylation of testicular eukaryotic translation initiation factor 2α (eIF2α), a downstream target of the double-stranded RNA-activated kinase-like ER kinase (PERK) pathway. In addition, NAC blocked the Cd-induced activation of testicular X binding protein (XBP)-1, indicating that NAC attenuates the Cd-induced ER stress and the unfolded protein response (UPR). Interestingly, NAC almost completely prevented the Cd-induced elevation of C/EBP homologous protein (CHOP) and phosphorylation of c-Jun N-terminal kinase (JNK), two components of the ER stress-mediated apoptotic pathway. In conclusion, NAC protects against Cd-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in the testes.

  6. Phospholipase A2-treated human high-density lipoprotein and cholesterol movements: exchange processes and lecithin: cholesterol acyltransferase reactivity.

    Science.gov (United States)

    Chollet, F; Perret, B P; Chap, H; Douste-Blazy, L

    1986-02-12

    Human HDL3 (d 1.125-1.21 g/ml) were treated by an exogenous phospholipase A2 from Crotalus adamenteus in the presence of albumin. Phosphatidylcholine hydrolysis ranged between 30 and 90% and the reisolated particle was essentially devoid of lipolysis products. (1) An exchange of free cholesterol was recorded between radiolabelled erythrocytes at 5-10% haematocrit and HDL3 (0.6 mM total cholesterol) from 0 to 12-15 h. Isotopic equilibration was reached. Kinetic analysis of the data indicated a constant rate of free cholesterol exchange of 13.0 microM/h with a half-time of equilibration around 3 h. Very similar values of cholesterol exchange, specific radioactivities and kinetic parameters were measured when phospholipase-treated HDL replaced control HDL. (2) The lecithin: cholesterol acyltransferase reactivity of HDL3, containing different amounts of phosphatidylcholine, as achieved by various degrees of phospholipase A2 treatment, was measured using a crude preparation of lecithin: cholesterol acyltransferase (the d 1.21-1.25 g/ml plasma fraction). The rate of esterification was determined between 0 and 12 h. Following a 15-30% lipolysis, the lecithin: cholesterol acyltransferase reactivity of HDL3 was reduced about 30-40%, and then continued to decrease, though more slowly, as the phospholipid content was further lowered in the particle. (3) The addition of the lecithin: cholesterol acyltransferase preparation into an incubation medium made of labelled erythrocytes and HDL3 promoted a movement of radioactive cholesterol out of cells, above the values of exchange, and an accumulation of cholesteryl esters in HDL. This reflected a mass consumption of free cholesterol, from both the cellular and the lipoprotein compartments upon the lecithin: cholesterol acyltransferase action. As a consequence of a decreased reactivity, phospholipase-treated HDL (with 2/3 of phosphatidylcholine hydrolyzed) proved much less effective in the lecithin: cholesterol acyltransferase-induced

  7. Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol.

    Science.gov (United States)

    Xiao, Changting; Dash, Satya; Morgantini, Cecilia; Hegele, Robert A; Lewis, Gary F

    2016-07-01

    Notwithstanding the effectiveness of lowering LDL cholesterol, residual CVD risk remains in high-risk populations, including patients with diabetes, likely contributed to by non-LDL lipid abnormalities. In this Perspectives in Diabetes article, we emphasize that changing demographics and lifestyles over the past few decades have resulted in an epidemic of the "atherogenic dyslipidemia complex," the main features of which include hypertriglyceridemia, low HDL cholesterol levels, qualitative changes in LDL particles, accumulation of remnant lipoproteins, and postprandial hyperlipidemia. We briefly review the underlying pathophysiology of this form of dyslipidemia, in particular its association with insulin resistance, obesity, and type 2 diabetes, and the marked atherogenicity of this condition. We explain the failure of existing classes of therapeutic agents such as fibrates, niacin, and cholesteryl ester transfer protein inhibitors that are known to modify components of the atherogenic dyslipidemia complex. Finally, we discuss targeted repurposing of existing therapies and review promising new therapeutic strategies to modify the atherogenic dyslipidemia complex. We postulate that targeting the central abnormality of the atherogenic dyslipidemia complex, the elevation of triglyceride-rich lipoprotein particles, represents a new frontier in CVD prevention and is likely to prove the most effective strategy in correcting most aspects of the atherogenic dyslipidemia complex, thereby preventing CVD events. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  8. Garlic extracts prevent oxidative stress, hypertrophy and apoptosis in cardiomyocytes: a role for nitric oxide and hydrogen sulfide

    Science.gov (United States)

    2012-01-01

    Background In ancient times, plants were recognized for their medicinal properties. Later, the arrival of synthetic drugs pushed it to the backstage. However, from being merely used for food, plants are now been widely explored for their therapeutic value. The current study explores the potential of skin and flesh extracts from a hard-necked Rocambole variety of purple garlic in preventing cardiomyocyte hypertrophy and cell death. Methods Norepinephrine (NE) was used to induce hypertrophy in adult rat cardiomyocytes pretreated with garlic skin and flesh extracts. Cell death was measured as ratio of rod to round shaped cardiomyocytes. Fluorescent probes were used to measure apoptosis and oxidative stress in cardiomyocytes treated with and without extracts and NE. Pharmacological blockade of nitric oxide (NO) and hydrogen sulfide (H2S) were used to elucidate the mechanism of action of garlic extracts. Garlic extract samples were also tested for alliin and allicin concentrations. Results Exposure of cardiomyocytes to NE induced an increase in cell size and cell death; this increase was significantly prevented upon treatment with garlic skin and flesh extracts. Norepinephrine increased apoptosis and oxidative stress in cardiomyocytes which was prevented upon pretreatment with skin and flesh extracts; NO, and H2S blockers significantly inhibited this beneficial effect. Allicin and alliin concentration were significantly higher in garlic flesh extract when compared to the skin extract. Conclusion These results suggest that both skin and flesh garlic extracts are effective in preventing NE induced cardiomyocyte hypertrophy and cell death. Reduction in oxidative stress may also play an important role in the anti-hypertrophic and anti-apoptotic properties of garlic extracts. These beneficial effects may in part be mediated by NO and H2S. PMID:22931510

  9. Lead nitrate-induced development of hypercholesterolemia in rats: sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis.

    Science.gov (United States)

    Kojima, Misaki; Masui, Toshimitsu; Nemoto, Kiyomitsu; Degawa, Masakuni

    2004-12-01

    Changes in the gene expressions of hepatic enzymes responsible for cholesterol homeostasis were examined during the process of lead nitrate (LN)-induced development of hypercholesterolemia in male rats. Total cholesterol levels in the liver and serum were significantly increased at 3-72 h and 12-72 h, respectively, after LN-treatment (100 micromol/kg, i.v.). Despite the development of hypercholesterolemia, the genes for hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and other enzymes (FPPS, farnesyl diphosphate synthase; SQS, squalene synthase; CYP51, lanosterol 14alpha-demethylase) responsible for cholesterol biosynthesis were activated at 3-24 h and 12-18 h, respectively. On the other hand, the gene expression of cholesterol 7alpha-hydroxylase (CYP7A1), a catabolic enzyme of cholesterol, was remarkably suppressed at 3-72 h. The gene expression levels of cytokines interleukin-1beta (IL-1beta) and TNF-alpha, which activate the HMGR gene and suppress the CYP7A1 gene, were significantly increased at 1-3 h and 3-24 h, respectively. Furthermore, gene activation of SREBP-2, a gene activator of several cholesterogenic enzymes, occurred before the gene activations of FPPS, SQS and CYP51. This is the first report demonstrating sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis in LN-treated male rats. The mechanisms for the altered-gene expressions of hepatic enzymes in LN-treated rats are discussed.

  10. Association of soluble Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) with central adiposity and low-density lipoprotein cholesterol.

    Science.gov (United States)

    Brombo, Gloria; Volpato, Stefano; Secchiero, Paola; Passaro, Angelina; Bosi, Cristina; Zuliani, Giovanni; Zauli, Giorgio

    2013-01-01

    Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL), in addition to having a prognostic value in patients with cardiovascular disease, seems to interact with adiposity, insulin resistance and other cardiovascular risk factors. However, the results of previous clinical studies, focused on the association of TRAIL with selected metabolic or anthropometric indices were inconclusive. The aim of this study was to further investigate how soluble TRAIL concentrations independently correlate with major cardiovascular risk factors, including lipid, glycemic and anthropometric features. We examined the associations between serum soluble TRAIL concentrations, measured by ELISA, and lipid, glycemic and anthropometric features in 199 subjects recruited at our Metabolic Outpatient Clinic. Soluble TRAIL concentrations had a significant and direct correlation with total cholesterol (p = 0.046), LDL-cholesterol (p = 0.032), triglycerides (p = 0.01), body mass index (p = 0.046), waist circumference (p = 0.008), fat mass (p = 0.056) and insulin (p = 0.046) and an inverse correlation with HDL-cholesterol (p = 0.02). In multivariable regression analyses adjusted for potential confounders (age, gender, C-reactive protein, HDL-cholesterol, triglycerides, waist circumference, and insulin), TRAIL levels continued to have an independent correlation with LDL-cholesterol and waist circumference (r(2) = 0.04). Serum TRAIL levels were weakly but significantly and independently associated with waist circumference, a marker of visceral adiposity, and with LDL-cholesterol. Further studies are needed to clarify the biological basis of these relationships.

  11. Cholesterol impairment contributes to neuroserpin aggregation

    Science.gov (United States)

    Giampietro, Costanza; Lionetti, Maria Chiara; Costantini, Giulio; Mutti, Federico; Zapperi, Stefano; La Porta, Caterina A. M.

    2017-03-01

    Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer’s and Parkinson’s diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol reg-ulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.

  12. Beneficial Effect of Jojoba Seed Extracts on Hyperglycemia-Induced Oxidative Stress in RINm5f Beta Cells.

    Science.gov (United States)

    Belhadj, Sahla; Hentati, Olfa; Hamdaoui, Ghaith; Fakhreddine, Khaskhoussi; Maillard, Elisa; Dal, Stéphanie; Sigrist, Séverine

    2018-03-20

    Hyperglycemia occurs during diabetes and insulin resistance. It causes oxidative stress by increasing reactive oxygen species (ROS) levels, leading to cellular damage. Polyphenols play a central role in defense against oxidative stress. In our study, we investigated the antioxidant properties of simmondsin, a pure molecule present in jojoba seeds, and of the aqueous extract of jojoba seeds on fructose-induced oxidative stress in RINm5f beta cells. The exposure of RINm5f beta cells to fructose triggered the loss of cell viability (-48%, p jojoba seed extract makes jojoba a powerful agent to prevent the destruction of RINm5f beta cells induced by hyperglycemia.

  13. Diet and Age Interactions with Regards to Cholesterol Regulation and Brain Pathogenesis

    Directory of Open Access Journals (Sweden)

    Romina M. Uranga

    2010-01-01

    Full Text Available Cholesterol is an essential molecule for brain homeostasis; yet, hypercholesterolemia and its numerous complications are believed to play a role in promoting multiple aspects of brain pathogenesis. An ever increasing number of individuals in modern Western Society are regularly consuming diets high in fat which promote the development of hypercholesterolemia. Additionally, modern societies are becoming increasingly aged, causing a collision between increased hypercholesterolemia and increased aging, which will likely lead to the development of increased pathological conditions due to hypercholesterolemia, thereby promoting deleterious neurochemical and behavioral changes in the brain. Lastly, while beneficial in controlling cholesterol levels, the long-term use of statins itself may potentially promote adverse effects on brain homeostasis, although specifics on this remain largely unknown. This review will focus on linking the current understanding of diet-induced hypercholesterolemia (as well as statin use to the development of oxidative stress, neurochemical alterations, and cognitive disturbances in the aging brain.

  14. Sex and stress: Men and women show different cortisol responses to psychological stress induced by the Trier social stress test and the Iowa singing social stress test.

    Science.gov (United States)

    Reschke-Hernández, Alaine E; Okerstrom, Katrina L; Bowles Edwards, Angela; Tranel, Daniel

    2017-01-02

    Acute psychological stress affects each of us in our daily lives and is increasingly a topic of discussion for its role in mental illness, aging, cognition, and overall health. A better understanding of how such stress affects the body and mind could contribute to the development of more effective clinical interventions and prevention practices. Over the past 3 decades, the Trier Social Stress Test (TSST) has been widely used to induce acute stress in a laboratory setting based on the principles of social evaluative threat, namely, a judged speech-making task. A comparable alternative task may expand options for examining acute stress in a controlled laboratory setting. This study uses a within-subjects design to examine healthy adult participants' (n = 20 men, n = 20 women) subjective stress and salivary cortisol responses to the standard TSST (involving public speaking and math) and the newly created Iowa Singing Social Stress Test (I-SSST). The I-SSST is similar to the TSST but with a new twist: public singing. Results indicated that men and women reported similarly high levels of subjective stress in response to both tasks. However, men and women demonstrated different cortisol responses; men showed a robust response to both tasks, and women displayed a lesser response. These findings are in line with previous literature and further underscore the importance of examining possible sex differences throughout various phases of research, including design, analysis, and interpretation of results. Furthermore, this nascent examination of the I-SSST suggests a possible alternative for inducing stress in the laboratory. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Pitavastatin Differentially Modulates MicroRNA-Associated Cholesterol Transport Proteins in Macrophages.

    Directory of Open Access Journals (Sweden)

    Haijun Zhang

    Full Text Available There is emerging evidence identifying microRNAs (miRNAs as mediators of statin-induced cholesterol efflux, notably through the ATP-binding cassette transporter A1 (ABCA1 in macrophages. The objective of this study was to assess the impact of an HMG-CoA reductase inhibitor, pitavastatin, on macrophage miRNAs in the presence and absence of oxidized-LDL, a hallmark of a pro-atherogenic milieu. Treatment of human THP-1 cells with pitavastatin prevented the oxLDL-mediated suppression of miR-33a, -33b and -758 mRNA in these cells, an effect which was not uniquely attributable to induction of SREBP2. Induction of ABCA1 mRNA and protein by oxLDL was inhibited (30% by pitavastatin, while oxLDL or pitavastatin alone significantly induced and repressed ABCA1 expression, respectively. These findings are consistent with previous reports in macrophages. miRNA profiling was also performed using a miRNA array. We identified specific miRNAs which were up-regulated (122 and down-regulated (107 in THP-1 cells treated with oxLDL plus pitavastatin versus oxLDL alone, indicating distinct regulatory networks in these cells. Moreover, several of the differentially expressed miRNAs identified are functionally associated with cholesterol trafficking (six miRNAs in cells treated with oxLDL versus oxLDL plus pitavastatin. Our findings indicate that pitavastatin can differentially modulate miRNA in the presence of oxLDL; and, our results provide evidence that the net effect on cholesterol homeostasis is mediated by a network of miRNAs.

  16. Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

    2015-08-28

    Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

  17. Effect of the hexane extract of Piper auritum on insulin release from β-cell and oxidative stress in streptozotocin-induced diabetic rat.

    Science.gov (United States)

    Gutierrez, Rosa Martha Perez

    2012-10-01

    The large-leafed perennial plant Piper auritum known as Hoja Santa, is used for its leaves that because of their spicy aromatic scent and flavor have an important presence in Mexican cuisine, and in many regions, this plant is known for its therapeutic properties. In the present study, we investigated the effect of hexane, chloroform and methanol extracts from Piper auritum on cell culture system and the effect in streptozotocin-induced type 1 diabetic rats treated by 28 days on the physiological, metabolic parameters and oxidative stress. The hexane extract of P. auritum (HS) treatment significantly reduced the intake of both food, water and body weight loss as well as levels of blood glucose, serum cholesterol, triglycerides and increase HDL-cholesterol. After 4-week administration of HS antioxidant enzyme as SOD, CAT, GSH, GPx in pancreas were determined. These enzyme increased significantly compared with those of the diabetic rats control and normal animals. For all estimated, the results of HS treated groups leading to a restoration of the defense mechanism. The treatment also improves pancreatic TBARS-reactive substance level and serum NO and iNOS. To determine the insulin releasing activity, after extract treatment the serum and pancreatic sections were processed for examination of insulin-releasing activity using an immunocytochemistry kit. The results showed that administration of the hexane extract (200 and 400 mg/kg) exhibited a significant increase in serum and pancreas tissue insulin. Administration of streptozotocin decreased the insulin secretory activity in comparison with intact rats, but treatment with the HS extract increased significantly the activity of the beta cells in comparison with the diabetic control rats. The extract decreased serum glucose in streptozotocin-induced diabetic rats and increased insulin release from the beta cells of the pancreas. In cultured RIN-5F cells, we examined whether hexane extract of P. auritum would protect the

  18. Pine needle extract prevents hippocampal memory impairment in acute restraint stress mouse model.

    Science.gov (United States)

    Lee, Jin-Seok; Kim, Hyeong-Geug; Lee, Hye-Won; Kim, Won-Yong; Ahn, Yo-Chan; Son, Chang-Gue

    2017-07-31

    The Pinus densiflora leaf has been traditionally used to treat mental health disorders as a traditional Chinese medicine. Here we examined the ethnopharmacological relevance of pine needle on memory impairment caused by stress. To elucidate the possible modulatory actions of 30% ethanolic pine needle extract (PNE) on stress-induced hippocampal excitotoxicity, we adopted an acute restraint stress mouse model. Mice were orally administered with PNE (25, 50, or 100mg/kg) or ascorbic acid (100mg/kg) for 9 days, and were then subjected to restraint stress (6h/day) for 3 days (from experimental day 7-9). To evaluate spatial cognitive and memory function, the Morris water maze was performed during experimental days 5-9. Restraint stress induced the memory impairment (the prolonged escape latency and cumulative path-length, and reduced time spent in the target quadrant), and these effects were significantly prevented by PNE treatment. The levels of corticosterone and its receptor in the sera/hippocampus were increased by restraint stress, which was normalized by PNE treatment. Restraint stress elicited the hippocampal excitotoxicity, the inflammatory response and oxidative injury as demonstrated by the increased glutamate levels, altered levels of tumor necrosis factor (TNF)-α and imbalanced oxidant-antioxidant balance biomarkers. Two immunohistochemistry activities against glial fibrillary acidic protein (GFAP)-positive astrocytes and neuronal nuclei (NeuN)-positive neurons supported the finding of excitotoxicity especially in the cornu ammonis (CA)3 region of the hippocampus. Those alterations were notably attenuated by administration of PNE. The above findings showed that PNE has pharmacological properties that modulate the hippocampal excitotoxicity-derived memory impairment under severe stress conditions. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  19. Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Ohara, Kazuaki, E-mail: Kazuaki_Ohara@kirin.co.jp [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Wakabayashi, Hideyuki [Laboratory for New Product Development, Kirin Beverage Company Limited, 1-17-1 Namamugi, Tsurumi-ku, Yokohama 230-8628 (Japan); Taniguchi, Yoshimasa [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Shindo, Kazutoshi [Department of Food and Nutrition, Japan Women’s University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681 (Japan); Yajima, Hiroaki [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Yoshida, Aruto [Central Laboratories for Key Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan)

    2013-11-29

    Highlights: •The major circulating quercetin metabolite (Q3GA) activated LXRα. •Q3GA induced ABCA1 via LXRα activation in macrophages. •Nelumbo nucifera leaf extracts contained quercetin glycosides. •N. nucifera leaf extract feeding elevated HDLC in mice. -- Abstract: Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRα), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found that quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRα in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.

  20. Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress.

    Science.gov (United States)

    Carda, Ana P P; Marchi, Katia C; Rizzi, Elen; Mecawi, André S; Antunes-Rodrigues, José; Padovan, Claudia M; Tirapelli, Carlos R

    2015-01-01

    We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B(2) (stable TXA(2) metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H(2)O(2)) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.

  1. Sulforaphane Prevents Angiotensin II-Induced Testicular Cell Death via Activation of NRF2

    Directory of Open Access Journals (Sweden)

    Yonggang Wang

    2017-01-01

    Full Text Available Although angiotensin II (Ang II was reported to facilitate sperm motility and intratesticular sperm transport, recent findings shed light on the efficacy of Ang II in stimulating inflammatory events in testicular peritubular cells, effect of which may play a role in male infertility. It is still unknown whether Ang II can induce testicular apoptotic cell death, which may be a more direct action of Ang II in male infertility. Therefore, the present study aims to determine whether Ang II can induce testicular apoptotic cell death and whether this action can be prevented by sulforaphane (SFN via activating nuclear factor (erythroid-derived 2-like 2 (NRF2, the governor of antioxidant-redox signalling. Eight-week-old male C57BL/6J wild type (WT and Nrf2 gene knockout mice were treated with Ang II, in the presence or absence of SFN. In WT mice, SFN activated testicular NRF2 expression and function, along with a marked attenuation in Ang II-induced testicular oxidative stress, inflammation, endoplasmic reticulum stress, and apoptotic cell death. Deletion of the Nrf2 gene led to a complete abolishment of these efficacies of SFN. The present study indicated that Ang II may result in testicular apoptotic cell death, which can be prevented by SFN via the activation of NRF2.

  2. Bile salt-induced cholesterol crystal formation from model bile vesicles: a time course study

    NARCIS (Netherlands)

    van de Heijning, B. J.; Stolk, M. F.; van Erpecum, K. J.; Renooij, W.; Groen, A. K.; vanBerge-Henegouwen, G. P.

    1994-01-01

    Precipitation of cholesterol crystals from vesicles is an important step in the pathogenesis of cholesterol gallstones. Little is known, however, about the kinetics and the mechanisms involved in cholesterol crystallization. Therefore, the time course of cholesterol crystal precipitation and lipid

  3. Hepatoprotective properties of kombucha tea against TBHP-induced oxidative stress via suppression of mitochondria dependent apoptosis.

    Science.gov (United States)

    Bhattacharya, Semantee; Gachhui, Ratan; Sil, Parames C

    2011-06-01

    Kombucha, a fermented tea (KT) is claimed to possess many beneficial properties. Recent studies have suggested that KT prevents paracetamol and carbon tetrachloride-induced hepatotoxicity. We investigated the beneficial role of KT was against tertiary butyl hydroperoxide (TBHP) induced cytotoxicity and cell death in murine hepatocytes. TBHP is a well known reactive oxygen species (ROS) inducer, and it induces oxidative stress in organ pathophysiology. In our experiments, TBHP caused a reduction in cell viability, enhanced the membrane leakage and disturbed the intra-cellular antioxidant machineries while simultaneous treatment of the cells with KT and this ROS inducer maintained membrane integrity and prevented the alterations in the cellular antioxidant status. These findings led us to explore the detailed molecular mechanisms involved in the protective effect of KT. TBHP introduced apoptosis as the primary phenomena of cell death as evidenced by flow cytometric analyses. In addition, ROS generation, changes in the mitochondrial membrane potential, cytochrome c release, activation of caspases (3 and 9) and Apaf-1 were detected confirming involvement of mitochondrial pathway in this pathophysiology. Simultaneous treatment of KT with TBHP, on the other hand, protected the cells against oxidative injury and maintained their normal physiology. In conclusion, KT was found to modulate the oxidative stress induced apoptosis in murine hepatocytes probably due to its antioxidant activity and functioning via mitochondria dependent pathways and could be beneficial against liver diseases, where oxidative stress is known to play a crucial role. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Antagonism of GABA-B but not GABA-A receptors in the VTA prevents stress- and intra-VTA CRF-induced reinstatement of extinguished cocaine seeking in rats.

    Science.gov (United States)

    Blacktop, Jordan M; Vranjkovic, Oliver; Mayer, Matthieu; Van Hoof, Matthew; Baker, David A; Mantsch, John R

    2016-03-01

    Stress-induced reinstatement of cocaine seeking requires corticotropin releasing factor (CRF) actions in the ventral tegmental area (VTA). However the mechanisms through which CRF regulates VTA function to promote cocaine use are not fully understood. Here we examined the role of GABAergic neurotransmission in the VTA mediated by GABA-A or GABA-B receptors in the reinstatement of extinguished cocaine seeking by a stressor, uncontrollable intermittent footshock, or bilateral intra-VTA administration of CRF. Rats underwent repeated daily cocaine self-administration (1.0 mg/kg/ing; 14 × 6 h/day) and extinction and were tested for reinstatement in response to footshock (0.5 mA, 0.5" duration, average every 40 s; range 10-70 s) or intra-VTA CRF delivery (500 ng/side) following intra-VTA pretreatment with the GABA-A antagonist, bicuculline, the GABA-B antagonist, 2-hydroxysaclofen or vehicle. Intra-VTA bicuculline (1, 10 or 20 ng/side) failed to block footshock- or CRF-induced cocaine seeking at either dose tested. By contrast, 2-hydroxysaclofen (0.2 or 2 μg/side) prevented reinstatement by both footshock and intra-VTA CRF at a concentration that failed to attenuate food-reinforced lever pressing (45 mg sucrose-sweetened pellets; FR4 schedule) in a separate group of rats. These data suggest that GABA-B receptor-dependent CRF actions in the VTA mediate stress-induced cocaine seeking and that GABA-B receptor antagonists may have utility for the management of stress-induced relapse in cocaine addicts. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Ursodeoxycholic Acid (UDCA) Exerts Anti-Atherogenic Effects by Inhibiting Endoplasmic Reticulum (ER) Stress Induced by Disturbed Flow.

    Science.gov (United States)

    Chung, Jihwa; Kim, Kyoung Hwa; Lee, Seok Cheol; An, Shung Hyun; Kwon, Kihwan

    2015-10-01

    Disturbed blood flow with low-oscillatory shear stress (OSS) is a predominant atherogenic factor leading to dysfunctional endothelial cells (ECs). Recently, it was found that disturbed flow can directly induce endoplasmic reticulum (ER) stress in ECs, thereby playing a critical role in the development and progression of atherosclerosis. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid, has long been used to treat chronic cholestatic liver disease and is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, its role in atherosclerosis remains unexplored. In this study, we demonstrated the anti-atherogenic activity of UDCA via inhibition of disturbed flow-induced ER stress in atherosclerosis. UDCA effectively reduced ER stress, resulting in a reduction in expression of X-box binding protein-1 (XBP-1) and CEBP-homologous protein (CHOP) in ECs. UDCA also inhibits the disturbed flow-induced inflammatory responses such as increases in adhesion molecules, monocyte adhesion to ECs, and apoptosis of ECs. In a mouse model of disturbed flow-induced atherosclerosis, UDCA inhibits atheromatous plaque formation through the alleviation of ER stress and a decrease in adhesion molecules. Taken together, our results revealed that UDCA exerts anti-atherogenic activity in disturbed flow-induced atherosclerosis by inhibiting ER stress and the inflammatory response. This study suggests that UDCA may be a therapeutic agent for prevention or treatment of atherosclerosis.

  6. Exercise Training Prevents Cardiovascular Derangements Induced by Fructose Overload in Developing Rats.

    Directory of Open Access Journals (Sweden)

    Daniela Farah

    Full Text Available The risks of chronic diseases associated with the increasing consumption of fructose-laden foods are amplified by the lack of regular physical activity and have become a serious public health issue worldwide. Moreover, childhood eating habits are strongly related to metabolic syndrome in adults. Thus, we aimed to investigate the preventive role of exercise training undertaken concurrently with a high fructose diet on cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in male rats after weaning. Male Wistar rats were divided into 4 groups (n = 8/group: Sedentary control (SC, Trained control (TC, Sedentary Fructose (SF and Trained Fructose (TF. Training was performed on a treadmill (8 weeks, 40-60% of maximum exercise test. Evaluations of cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in plasma and in left ventricle (LV were performed. Chronic fructose overload induced glucose intolerance and an increase in white adipose tissue (WAT weight, in myocardial performance index (MPI (SF:0.42±0.04 vs. SC:0.24±0.05 and in arterial pressure (SF:122±3 vs. SC:113±1 mmHg associated with increased cardiac and vascular sympathetic modulation. Fructose also induced unfavorable changes in oxidative stress profile (plasmatic protein oxidation- SF:3.30±0.09 vs. SC:1.45±0.08 nmol/mg prot; and LV total antioxidant capacity (TRAP- SF: 2.5±0.5 vs. SC:12.7±1.7 uM trolox. The TF group showed reduced WAT, glucose intolerance, MPI (0.35±0.04, arterial pressure (118±2mmHg, sympathetic modulation, plasmatic protein oxidation and increased TRAP when compared to SF group. Therefore, our findings indicate that cardiometabolic dysfunctions induced by fructose overload early in life may be prevented by moderate aerobic exercise training.

  7. Exercise Training Prevents Cardiovascular Derangements Induced by Fructose Overload in Developing Rats

    Science.gov (United States)

    Farah, Daniela; Nunes, Jonas; Sartori, Michelle; Dias, Danielle da Silva; Sirvente, Raquel; Silva, Maikon B.; Fiorino, Patrícia; Morris, Mariana; Llesuy, Susana; Farah, Vera; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2016-01-01

    The risks of chronic diseases associated with the increasing consumption of fructose-laden foods are amplified by the lack of regular physical activity and have become a serious public health issue worldwide. Moreover, childhood eating habits are strongly related to metabolic syndrome in adults. Thus, we aimed to investigate the preventive role of exercise training undertaken concurrently with a high fructose diet on cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in male rats after weaning. Male Wistar rats were divided into 4 groups (n = 8/group): Sedentary control (SC), Trained control (TC), Sedentary Fructose (SF) and Trained Fructose (TF). Training was performed on a treadmill (8 weeks, 40–60% of maximum exercise test). Evaluations of cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in plasma and in left ventricle (LV) were performed. Chronic fructose overload induced glucose intolerance and an increase in white adipose tissue (WAT) weight, in myocardial performance index (MPI) (SF:0.42±0.04 vs. SC:0.24±0.05) and in arterial pressure (SF:122±3 vs. SC:113±1 mmHg) associated with increased cardiac and vascular sympathetic modulation. Fructose also induced unfavorable changes in oxidative stress profile (plasmatic protein oxidation- SF:3.30±0.09 vs. SC:1.45±0.08 nmol/mg prot; and LV total antioxidant capacity (TRAP)- SF: 2.5±0.5 vs. SC:12.7±1.7 uM trolox). The TF group showed reduced WAT, glucose intolerance, MPI (0.35±0.04), arterial pressure (118±2mmHg), sympathetic modulation, plasmatic protein oxidation and increased TRAP when compared to SF group. Therefore, our findings indicate that cardiometabolic dysfunctions induced by fructose overload early in life may be prevented by moderate aerobic exercise training. PMID:27930685

  8. Cholesterol modulates the cellular localization of Orai1 channels and its disposition among membrane domains.

    Science.gov (United States)

    Bohórquez-Hernández, A; Gratton, Enrico; Pacheco, Jonathan; Asanov, Alexander; Vaca, Luis

    2017-12-01

    Store Operated Calcium Entry (SOCE) is one of the most important mechanisms for calcium mobilization in to the cell. Two main proteins sustain SOCE: STIM1 that acts as the calcium sensor in the endoplasmic reticulum (ER) and Orai1 responsible for calcium influx upon depletion of ER. There are many studies indicating that SOCE is modulated by the cholesterol content of the plasma membrane (PM). However, a myriad of questions remain unanswered concerning the precise molecular mechanism by which cholesterol modulates SOCE. In the present study we found that reducing PM cholesterol results in the internalization of Orai1 channels, which can be prevented by overexpressing caveolin 1 (Cav1). Furthermore, Cav1 and Orai1 associate upon SOCE activation as revealed by FRET and coimmunoprecipitation assays. The effects of reducing cholesterol were not limited to an increased rate of Orai1 internalization, but also, affects the lateral movement of Orai1, inducing movement in a linear pattern (unobstructed diffusion) opposite to basal cholesterol conditions were most of Orai1 channels moves in a confined space, as assessed by Fluorescence Correlation Spectroscopy, Cav1 overexpression inhibited these alterations maintaining Orai1 into a confined and partially confined movement. These results not only highlight the complex effect of cholesterol regulation on SOCE, but also indicate a direct regulatory effect on Orai1 localization and compartmentalization by this lipid. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Inhibitory effects of viburnum dilatatum Thunb. (gamazumi) on oxidation and hyperglycemia in rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Iwai, Kunihisa; Onodera, Akio; Matsue, Hajime

    2004-02-25

    The fruit of Viburnum dilatatum Thunb. (gamazumi) was found in a previous study to have strong radical scavenging activity. The present study investigated the antioxidative functions of gamazumi crude extract (GCE) in rats having diabetes induced by the administration of streptozotocin. In rats given water (H(2)O group), plasma levels of glucose, total cholesterol, and lipid peroxide (TBARS) and erythrocyte levels of TBARS increased with time over the experimental period of 10 weeks. These increases were inhibited in rats given GCE (GCE group). After 10 weeks, hepatic, renal, and pancreatic TBARS in the GCE group were significantly lower than those in the H(2)O group. GCE contains a high concentration of polyphenols, and it is expected that they are the active components. These results demonstrate that GCE has an inhibitory effect on the oxidative stress induced by diabetes and suggest that GCE may be useful for the prevention of diabetic complications. Furthermore, as the increase of plasma glucose and total cholesterol was inhibited in the GCE group, GCE may also have anti-hyperglycemic activity in diabetes.

  10. Lack of Cholesterol Awareness among Physicians Who Smoke

    Directory of Open Access Journals (Sweden)

    Richard E. Scranton

    2009-02-01

    Full Text Available Cigarette use is a known risk factor for the development of coronary artery disease (CAD as it adversely affects HDL cholesterol levels and promotes thrombogenesis. Smoking may also be associated with behavioral characteristics that potentiate the risk of CAD. A lack of cholesterol knowledge would indicate an aversion to a prevention-oriented lifestyle. Thus, our goal was to determine the association between tobacco use and knowledge of self-reported cholesterol among male physicians. Using the 1982 and follow-up questionnaires from the physician health study, we report the changes in the frequencies of awareness of self-reported total cholesterol and cardiovascular risk factors among the 22,067 participants. We classified physicians as being aware of their cholesterol if they reported a cholesterol level and unaware if the question was left unanswered. In 1997, 207 physicians were excluded, as the recorded cholesterol was not interpretable, leaving 21,860 for our follow up analyses. Using unadjusted logistic models, we determined the odds ratios (OR and 95% confidence intervals (CI of not reporting a cholesterol level in either 1982 or 1997 for each specified risk factor. We then evaluated whether the lack of cholesterol awareness at both time points was associated with the use of tobacco throughout the study. After 14-years of follow up, cholesterol awareness increased from 35.9 to 58.6 percent. During this period, the frequency of hypertension and hyperlipidemia treatment increased (13.5 to 40.5% and 0.57% to 19.6% respectively, as did the diagnosis of diabetes (2.40 to 7.79%. Behavioral characteristics such as a sedentary lifestyle and obesity also increased (27.8 to 42% and 43.5 to 53.5%, respectively, however the proportion of current smokers deceased from 11.1 to 4.05%. The percentages of individuals being unaware of their cholesterol decreased in all risk factor groups. However, individuals were likely to be unaware of their cholesterol

  11. Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

    DEFF Research Database (Denmark)

    Jørgensen, Henrik; Knigge, Ulrich; Kjaer, Andreas

    2002-01-01

    OBJECTIVE: To investigate the involvement of serotonin (5-hydroxytryptamine - 5-HT) receptors in mediation of stress-induced arginine vasopressin (AVP) and oxytocin (OT) secretion in male rats. DESIGN: Experiments on laboratory rats with control groups. METHODS: Different stress paradigms were...... the swim stress-induced OT response. CONCLUSION: 5-HT(2A), 5-HT(2C) and possibly 5-HT(3) and 5-HT(4) receptors, but not 5-HT(1A) receptors, are involved in the restraint stress-induced AVP secretion. 5-HT does not seem to be involved in the dehydration- or hemorrhage-induced AVP response. The restraint...... stress-induced OT response seems to be mediated via 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors. The dehydration and hemorrhage-induced OT responses are at least mediated by the 5-HT(2A) and 5-HT(2C) receptors. The 5-HT(3) and 5-HT(4) receptors are not involved in stress-induced OT secretion....

  12. Plumbagin, a vitamin K3 analogue, abrogates lipopolysaccharide-induced oxidative stress, inflammation and endotoxic shock via NF-κB suppression.

    Science.gov (United States)

    Checker, Rahul; Patwardhan, Raghavendra S; Sharma, Deepak; Menon, Jisha; Thoh, Maikho; Sandur, Santosh K; Sainis, Krishna B; Poduval, T B

    2014-04-01

    Plumbagin has been reported to modulate cellular redox status and suppress NF-κB. In the present study, we investigated the effect of plumbagin on lipopolysaccharide (LPS)-induced endotoxic shock, oxidative stress and inflammatory parameters in vitro and in vivo. Plumbagin inhibited LPS-induced nitric oxide, TNF-α, IL-6 and prostaglandin-E2 production in a concentration-dependent manner in RAW 264.7 cells without inducing any cell death. Plumbagin modulated cellular redox status in RAW cells. Plumbagin treatment significantly reduced MAPkinase and NF-κB activation in macrophages. Plumbagin prevented mice from endotoxic shock-associated mortality and decreased serum levels of pro-inflammatory markers. Plumbagin administration ameliorated LPS-induced oxidative stress in peritoneal macrophages and splenocytes. Plumbagin also attenuated endotoxic shock-associated changes in liver and lung histopathology and decreased the activation of ERK and NF-κB in liver. These findings demonstrate the efficacy of plumbagin in preventing LPS-induced endotoxemia and also provide mechanistic insights into the anti-inflammatory effects of plumbagin.

  13. Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid

    Energy Technology Data Exchange (ETDEWEB)

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C. [Bose Institute, Department of Chemistry, Kolkata, West Bengal (India)

    2008-03-15

    Arsenic, one of the most harmful metalloids, is ubiquitous in the environment. The present study has been carried out to investigate the protective role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced cardiac oxidative damage. In the study, NaAsO{sub 2} was chosen as the source of arsenic. The free radical scavenging activity and the effect of AA on the intracellular antioxidant power were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of NaAsO{sub 2} at a dose of 10 mg/kg body weight for 2 days caused significant accumulation of arsenic in cardiac tissues of the experimental mice in association with the reduction in cardiac antioxidant enzymes activities, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase. Arsenic intoxication also decreased the cardiac glutathione (GSH) and total thiol contents and increased the levels of oxidized glutathione (GSSG), lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20 mg/kg body weight for 4 days prior to NaAsO{sub 2} intoxication protected the cardiac tissue from arsenic-induced oxidative impairment. In addition to oxidative stress, arsenic administration increased total cholesterol level as well as the reduced high-density lipoprotein cholesterol level in the sera of the experimental mice. AA pretreatment, however, could prevent this hyperlipidemia. Histological studies on the ultrastructural changes in cardiac tissue supported the protective activity of AA also. Combining all, results suggest that AA could protect cardiac tissues against arsenic-induced oxidative stress probably due to its antioxidant property. (orig.)

  14. Indirubin-3-Oxime Prevents H2O2-Induced Neuronal Apoptosis via Concurrently Inhibiting GSK3β and the ERK Pathway.

    Science.gov (United States)

    Yu, Jie; Zheng, Jiacheng; Lin, Jiajia; Jin, Linlu; Yu, Rui; Mak, Shinghung; Hu, Shengquan; Sun, Hongya; Wu, Xiang; Zhang, Zaijun; Lee, Mingyuen; Tsim, Wahkeung; Su, Wei; Zhou, Wenhua; Cui, Wei; Han, Yifan; Wang, Qinwen

    2017-05-01

    Oxidative stress-induced neuronal apoptosis plays an important role in many neurodegenerative disorders. In this study, we have shown that indirubin-3-oxime, a derivative of indirubin originally designed for leukemia therapy, could prevent hydrogen peroxide (H 2 O 2 )-induced apoptosis in both SH-SY5Y cells and primary cerebellar granule neurons. H 2 O 2 exposure led to the increased activities of glycogen synthase kinase 3β (GSK3β) and extracellular signal-regulated kinase (ERK) in SH-SY5Y cells. Indirubin-3-oxime treatment significantly reversed the altered activity of both the PI3-K/Akt/GSK3β cascade and the ERK pathway induced by H 2 O 2 . In addition, both GSK3β and mitogen-activated protein kinase inhibitors significantly prevented H 2 O 2 -induced neuronal apoptosis. Moreover, specific inhibitors of the phosphoinositide 3-kinase (PI3-K) abolished the neuroprotective effects of indirubin-3-oxime against H 2 O 2 -induced neuronal apoptosis. These results strongly suggest that indirubin-3-oxime prevents H 2 O 2 -induced apoptosis via concurrent inhibiting GSK3β and the ERK pathway in SH-SY5Y cells, providing support for the use of indirubin-3-oxime to treat neurodegenerative disorders caused or exacerbated by oxidative stress.

  15. Exercise training attenuates sympathetic activation and oxidative stress in diet-induced obesity.

    Science.gov (United States)

    Li, G; Liu, J-Y; Zhang, H-X; Li, Q; Zhang, S-W

    2015-01-01

    It is known that excessive sympathetic activity and oxidative stress are enhanced in obesity. This study aimed to clarify whether exercise training (ET) attenuates sympathetic activation and oxidative stress in obesity. The obesity was induced by high-fat diet (HFD) for 12 weeks. Male Sprague-Dawley rats were assigned to four groups: regular diet (RD) plus sedentary (RD-S), RD plus ET (RD-ET), HFD plus sedentary (HFD-S), and HFD plus ET (HFD-ET). The rats in RD-ET and HFD-ET groups were trained on a motorized treadmill for 60 min/day, five days/week for 8 weeks. The sympathetic activity was evaluated by the plasma norepinephrine (NE) level. The superoxide anion, malondialdehyde and F2-isoprostanes levels in serum and muscles were measured to evaluate oxidative stress. The ET prevented the increases in the body weight, arterial pressure and white adipose tissue mass in HFD rats. The NE level in plasma and oxidative stress related parameters got lower in HFD-ET group compared with HFD-S group. We have found decreased mRNA and protein levels of toll-like receptor (TLR)-2 and TLR-4 by ET in HFD rats. These findings suggest that ET may be effective for attenuating sympathetic activation and oxidative stress in diet-induced obesity.

  16. Ameliorative Effects of Acacia Honey against Sodium Arsenite-Induced Oxidative Stress in Some Viscera of Male Wistar Albino Rats

    OpenAIRE

    Muhammad Aliyu; Sani Ibrahim; Hajiya M. Inuwa; Abdullahi B. Sallau; Olagunju Abbas; Idowu A. Aimola; Nathan Habila; Ndidi S. Uche

    2013-01-01

    Cancer is a leading cause of death worldwide and its development is frequently associated with oxidative stress-induced by carcinogens such as arsenicals. Most foods are basically health-promoting or disease-preventing and a typical example of such type is honey. This study was undertaken to investigate the ameliorative effects of Acacia honey on sodium arsenite-induced oxidative stress in the heart, lung and kidney tissues of male Wistar rats. Male Wistar albino rats divided into four groups...

  17. Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

    Science.gov (United States)

    Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

    2016-04-01

    Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  18. Prevention and Treatment of Noise-Induced Tinnitus

    Science.gov (United States)

    2014-09-01

    Tinnitus PRINCIPAL INVESTIGATOR: Dr. Richard A. Altschuler CONTRACTING ORGANIZATION: University of Michigan REPORT DATE: 2014...3 Ju 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prevention and Treatment of Noise-Induced Tinnitus 5b. GRANT NUMBER 5c. PROGRAM...prevent or treat noise induced tinnitus . Our studies showed a military relevant small arms fire-like noise will induce tinnitus in approximately 33

  19. Beta Blockers Suppress Dextrose-Induced Endoplasmic Reticulum Stress, Oxidative Stress, and Apoptosis in Human Coronary Artery Endothelial Cells.

    Science.gov (United States)

    Haas, Michael J; Kurban, William; Shah, Harshit; Onstead-Haas, Luisa; Mooradian, Arshag D

    Beta blockers are known to have favorable effects on endothelial function partly because of their capacity to reduce oxidative stress. To determine whether beta blockers can also prevent dextrose-induced endoplasmic reticulum (ER) stress in addition to their antioxidative effects, human coronary artery endothelial cells and hepatocyte-derived HepG2 cells were treated with 27.5 mM dextrose for 24 hours in the presence of carvedilol (a lipophilic beta blockers with alpha blocking activity), propranolol (a lipophilic nonselective beta blockers), and atenolol (a water-soluble selective beta blockers), and ER stress, oxidative, stress and cell death were measured. ER stress was measured using the placental alkaline phosphatase assay and Western blot analysis of glucose regulated protein 78, c-Jun-N-terminal kinase (JNK), phospho-JNK, eukaryotic initiating factor 2α (eIF2α), and phospho-eIF2α and measurement of X-box binding protein 1 (XBP1) mRNA splicing using reverse transcriptase-polymerase chain reaction. Superoxide (SO) generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride (MCLA) chemiluminescence. Cell viability was measured by propidium iodide staining method. The ER stress, SO production, and cell death induced by 27.5 mM dextrose were inhibited by all 3 beta blockers tested. The antioxidative and ER stress reducing effects of beta blockers were also observed in HepG2 cells. The salutary effects of beta blockers on endothelial cells in reducing both ER stress and oxidative stress may contribute to the cardioprotective effects of these agents.

  20. Curcumin reverses the depressive-like behavior and insulin resistance induced by chronic mild stress.

    Science.gov (United States)

    Shen, Ji-Duo; Wei, Yu; Li, Yu-Jie; Qiao, Jing-Yi; Li, Yu-Cheng

    2017-08-01

    Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity. Serum parameters were detected using commercial kits. Real-time quantitative PCR was used to examine mRNA expression. CMS rats exhibited reduced sucrose consumption, increased serum glucose, insulin, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), non-esterified fatty acid (NEFA), glucagon, leptin, and corticosterone levels, as well as impaired insulin sensitivity. Curcumin upregulated the phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (Akt) in the liver, enhanced insulin sensitivity, and reversed the metabolic abnormalities and depressive-like behaviors mentioned above. Moreover, curcumin increased the hepatic glycogen content by inhibiting glycogen synthase kinase (GSK)-3β and prevented gluconeogenesis by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). These results suggest that curcumin not only exerted antidepressant-like effects, but also reversed the insulin resistance and metabolic abnormalities induced by CMS. These data may provide evidence to support the potential use of curcumin against depression and/or metabolic disorders.

  1. Association of soluble Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL with central adiposity and low-density lipoprotein cholesterol.

    Directory of Open Access Journals (Sweden)

    Gloria Brombo

    Full Text Available OBJECTIVE: Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL, in addition to having a prognostic value in patients with cardiovascular disease, seems to interact with adiposity, insulin resistance and other cardiovascular risk factors. However, the results of previous clinical studies, focused on the association of TRAIL with selected metabolic or anthropometric indices were inconclusive. The aim of this study was to further investigate how soluble TRAIL concentrations independently correlate with major cardiovascular risk factors, including lipid, glycemic and anthropometric features. MATERIALS/METHODS: We examined the associations between serum soluble TRAIL concentrations, measured by ELISA, and lipid, glycemic and anthropometric features in 199 subjects recruited at our Metabolic Outpatient Clinic. RESULTS: Soluble TRAIL concentrations had a significant and direct correlation with total cholesterol (p = 0.046, LDL-cholesterol (p = 0.032, triglycerides (p = 0.01, body mass index (p = 0.046, waist circumference (p = 0.008, fat mass (p = 0.056 and insulin (p = 0.046 and an inverse correlation with HDL-cholesterol (p = 0.02. In multivariable regression analyses adjusted for potential confounders (age, gender, C-reactive protein, HDL-cholesterol, triglycerides, waist circumference, and insulin, TRAIL levels continued to have an independent correlation with LDL-cholesterol and waist circumference (r(2 = 0.04. CONCLUSIONS: Serum TRAIL levels were weakly but significantly and independently associated with waist circumference, a marker of visceral adiposity, and with LDL-cholesterol. Further studies are needed to clarify the biological basis of these relationships.

  2. Activation of the Hypoxia Inducible Factor 1α Subunit Pathway in Steatotic Liver Contributes to Formation of Cholesterol Gallstones.

    Science.gov (United States)

    Asai, Yoichiro; Yamada, Tetsuya; Tsukita, Sohei; Takahashi, Kei; Maekawa, Masamitsu; Honma, Midori; Ikeda, Masanori; Murakami, Keigo; Munakata, Yuichiro; Shirai, Yuta; Kodama, Shinjiro; Sugisawa, Takashi; Chiba, Yumiko; Kondo, Yasuteru; Kaneko, Keizo; Uno, Kenji; Sawada, Shojiro; Imai, Junta; Nakamura, Yasuhiro; Yamaguchi, Hiroaki; Tanaka, Kozo; Sasano, Hironobu; Mano, Nariyasu; Ueno, Yoshiyuki; Shimosegawa, Tooru; Katagiri, Hideki

    2017-05-01

    Hypoxia-inducible factor 1α subunit (HIF1A) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with nonalcoholic fatty liver disease (NAFLD). NAFLD increases the risk for cholesterol gallstone disease by unclear mechanisms. We studied the relationship between HIF1A and gallstone formation associated with liver steatosis. We performed studies with mice with inducible disruption of Hif1a in hepatocytes via a Cre adenoviral vector (inducible hepatocyte-selective HIF1A knockout [iH-HIFKO] mice), and mice without disruption of Hif1a (control mice). Mice were fed a diet rich in cholesterol and cholate for 1 or 2 weeks; gallbladders were collected and the number of gallstones was determined. Livers and biliary tissues were analyzed by histology, quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, and immunoblots. We measured concentrations of bile acid, cholesterol, and phospholipid in bile and rates of bile flow. Primary hepatocytes and cholangiocytes were isolated and analyzed. HIF1A was knocked down in Hepa1-6 cells with small interfering RNAs. Liver biopsy samples from patients with NAFLD, with or without gallstones, were analyzed by quantitative reverse-transcription polymerase chain reaction. Control mice fed a diet rich in cholesterol and cholate developed liver steatosis with hypoxia; levels of HIF1A protein were increased in hepatocytes around central veins and 90% of mice developed cholesterol gallstones. Only 20% of the iH-HIFKO mice developed cholesterol gallstones. In iH-HIFKO mice, the biliary lipid concentration was reduced by 36%, compared with control mice, and bile flow was increased by 35%. We observed increased water secretion from hepatocytes into bile canaliculi to mediate these effects, resulting in suppression of cholelithogenesis. Hepatic expression of aquaporin 8 (AQP8) protein was 1.5-fold higher in iH-HIFKO mice than in control mice. Under hypoxic

  3. Silymarin modulates doxorubicin-induced oxidative stress, Bcl-xL and p53 expression while preventing apoptotic and necrotic cell death in the liver

    International Nuclear Information System (INIS)

    Patel, Nirav; Joseph, Cecil; Corcoran, George B.; Ray, Sidhartha D.

    2010-01-01

    The emergence of silymarin (SMN) as a natural remedy for liver diseases, coupled with its entry into NIH clinical trial, signifies its hepatoprotective potential. SMN is noted for its ability to interfere with apoptotic signaling while acting as an antioxidant. This in vivo study was designed to explore the hepatotoxic potential of Doxorubicin (Dox), the well-known cardiotoxin, and in particular whether pre-exposures to SMN can prevent hepatotoxicity by reducing Dox-induced free radical mediated oxidative stress, by modulating expression of apoptotic signaling proteins like Bcl-xL, and by minimizing liver cell death occurring by apoptosis or necrosis. Groups of male ICR mice included Control, Dox alone, SMN alone, and Dox with SMN pre/co-treatment. Control and Dox groups received saline i.p. for 14 days. SMN was administered p.o. for 14 days at 16 mg/kg/day. An approximate LD 50 dose of Dox, 60 mg/kg, was administered i.p. on day 12 to animals receiving saline or SMN. Animals were euthanized 48 h later. Dox alone induced frank liver injury (> 50-fold increase in serum ALT) and oxidative stress (> 20-fold increase in malondialdehyde [MDA]), as well as direct damage to DNA (> 15-fold increase in DNA fragmentation). Coincident genomic damage and oxidative stress influenced genomic stability, reflected in increased PARP activity and p53 expression. Decreases in Bcl-xL protein coupled with enhanced accumulation of cytochrome c in the cytosol accompanied elevated indexes of apoptotic and necrotic cell death. Significantly, SMN exposure reduced Dox hepatotoxicity and associated apoptotic and necrotic cell death. The effects of SMN on Dox were broad, including the ability to modulate changes in both Bcl-xL and p53 expression. In animals treated with SMN, tissue Bcl-xL expression exceeded control values after Dox treatment. Taken together, these results demonstrated that SMN (i) reduced, delayed onset, or prevented toxic effects of Dox which are typically associated with

  4. Dietary and biliary cholesterol absorption in rats. Effect of dietary cholesterol level and cholesterol saturation of bile

    International Nuclear Information System (INIS)

    Wilson, M.D.

    1985-01-01

    The principal objective of this research was to determine if cholesterol introduced into the duodenum of rats in a micellar form as occurs with bile, is absorbed more efficiently than cholesterol presented in a nonmicellar form, as occurs with dietary cholesterol. Cholesterol absorption was measured during the constant intraduodenal infusion of liquid diets ([ 14 C] cholesterol) and artificial biles ([ 3 H] cholesterol) in thoracic lymph duct cannulated rats. Percentage absorption was calculated by dividing the rate of appearance of radiolabeled cholesterol in lymph by its rate of infusion when lymph cholesterol specific activity was constant. Results provide strong evidence that under certain conditions biliary cholesterol is more efficiently absorbed than is dietary cholesterol, and that this differential must be considered when evaluating the influence of diet or drug therapy on cholesterol absorption

  5. Beneficial Effects of Tianeptine on Hippocampus-Dependent Long-Term Memory and Stress-Induced Alterations of Brain Structure and Function

    Science.gov (United States)

    Zoladz, Phillip R.; Muñoz, Carmen; Diamond, David M.

    2010-01-01

    Tianeptine is a well-described antidepressant which has been shown to prevent stress from producing deleterious effects on brain structure and function. Preclinical studies have shown that tianeptine blocks stress-induced alterations of neuronal morphology and synaptic plasticity. Moreover, tianeptine prevents stress from impairing learning and memory, and, importantly, demonstrates memory-enhancing properties in the absence of stress. Recent research has indicated that tianeptine works by normalizing glutamatergic neurotransmission, a mechanism of action that may underlie its effectiveness as an antidepressant. These findings emphasize the value in focusing on the mechanisms of action of tianeptine, and specifically, the glutamatergic system, in the development of novel pharmacotherapeutic strategies in the treatment of depression.

  6. Beneficial Effects of Tianeptine on Hippocampus-Dependent Long-Term Memory and Stress-Induced Alterations of Brain Structure and Function

    Directory of Open Access Journals (Sweden)

    Carmen Muñoz

    2010-10-01

    Full Text Available Tianeptine is a well-described antidepressant which has been shown to prevent stress from producing deleterious effects on brain structure and function. Preclinical studies have shown that tianeptine blocks stress-induced alterations of neuronal morphology and synaptic plasticity. Moreover, tianeptine prevents stress from impairing learning and memory, and, importantly, demonstrates memory-enhancing properties in the absence of stress. Recent research has indicated that tianeptine works by normalizing glutamatergic neurotransmission, a mechanism of action that may underlie its effectiveness as an antidepressant. These findings emphasize the value in focusing on the mechanisms of action of tianeptine, and specifically, the glutamatergic system, in the development of novel pharmacotherapeutic strategies in the treatment of depression.

  7. DIETARY FISH-OIL POTENTIATES BILE ACID-INDUCED CHOLESTEROL SECRETION INTO BILE IN RATS

    NARCIS (Netherlands)

    SMIT, MJ; VERKADE, HJ; HAVINGA, R; VONK, RJ; SCHERPHOF, GL; TVELD, GI; KUIPERS, F

    Recently we demonstrated that dietary fish oil (FO) causes changes in intrahepatic cholesterol transport and hyper secretion of cholesterol into bile in rats V. Clin. Invest. 88: 943-951, 1991). We have now investigated in more detail the relationship between cholesterol and bile acid secretion in

  8. Effects of Gladiolus dalenii on the Stress-Induced Behavioral, Neurochemical, and Reproductive Changes in Rats

    Directory of Open Access Journals (Sweden)

    David Fotsing

    2017-09-01

    Full Text Available Gladiolus dalenii is a plant commonly used in many regions of Cameroon as a cure for various diseases like headaches, epilepsy, schizophrenia, and mood disorders. Recent studies have revealed that the aqueous extract of G. dalenii (AEGD exhibited antidepressant-like properties in rats. Therefore, we hypothesized that the AEGD could protect from the stress-induced behavioral, neurochemical, and reproductive changes in rats. The objective of the present study was to elucidate the effect of the AEGD on behavioral, neurochemical, and reproductive characteristics, using female rats subjected to chronic immobilization stress. The chronic immobilization stress (3 h per day for 28 days was applied to induce female reproductive and behavioral impairments in rats. The immobilization stress was provoked in rats by putting them separately inside cylindrical restrainers with ventilated doors at ambient temperature. The plant extract was given to rats orally everyday during 28 days, 5 min before induction of stress. On a daily basis, a vaginal smear was made to assess the duration of the different phases of the estrous cycle and at the end of the 28 days of chronic immobilization stress, the rat’s behavior was assessed in the elevated plus maze. They were sacrificed by cervical disruption. The organs were weighed, the ovary histology done, and the biochemical parameters assessed. The findings of this research revealed that G. dalenii increased the entries and the time of open arm exploration in the elevated plus maze. Evaluation of the biochemical parameters levels indicated that there was a significant reduction in the corticosterone, progesterone, and prolactin levels in the G. dalenii aqueous extract treated rats compared to stressed rats whereas the levels of serotonin, triglycerides, adrenaline, cholesterol, glucose estradiol, follicle stimulating hormone and luteinizing hormone were significantly increased in the stressed rats treated with, G. dalenii

  9. Stress-induced magnetic anisotropy in nanocrystalline alloys

    International Nuclear Information System (INIS)

    Varga, L.K.; Gercsi, Zs.; Kovacs, Gy.; Kakay, A.; Mazaleyrat, F.

    2003-01-01

    Stress-annealing experiments were extended to both nanocrystalline alloy families, Finemet and Nanoperm (Hitperm), and, for comparison, to amorphous Fe 62 Nb 8 B 30 alloy. For both Finemet and bulk amorphous, stress-annealing results in a strong induced transversal anisotropy (flattening of hysteresis loop) but yields longitudinal induced anisotropy (square hysteresis loop) in Nanoperm and Hitperm. These results are interpreted in terms of back-stress theory

  10. Knockdown of ventral tegmental area mu-opioid receptors in rats prevents effects of social defeat stress: Implications for amphetamine cross-sensitization, social avoidance, weight regulation and expression of brain-derived neurotrophic factor

    Science.gov (United States)

    Johnston, Caitlin E.; Herschel, Daniel; Lasek, Amy W.; Hammer, Ronald P.; Nikulina, Ella M.

    2014-01-01

    Social defeat stress causes social avoidance and long-lasting cross-sensitization to psychostimulants, both of which are associated with increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). Moreover, social stress upregulates VTA mu-opioid receptor (MOR) mRNA. In the VTA, MOR activation inhibits GABA neurons to disinhibit VTA dopamine neurons, thus providing a role for VTA MORs in the regulation of psychostimulant sensitization. The present study determined the effect of lentivirus-mediated MOR knockdown in the VTA on the consequences of intermittent social defeat stress, a salient and profound stressor in humans and rodents. Social stress exposure induced social avoidance and attenuated weight gain in animals with non-manipulated VTA MORs, but both these effects were prevented by VTA MOR knockdown. Rats with non-manipulated VTA MOR expression exhibited cross-sensitization to amphetamine challenge (1.0 mg/kg, i.p.), evidenced by a significant augmentation of locomotion. By contrast, knockdown of VTA MORs prevented stress-induced cross-sensitization without blunting the locomotor-activating effects of amphetamine. At the time point corresponding to amphetamine challenge, immunohistochemical analysis was performed to examine the effect of stress on VTA BDNF expression. Prior stress exposure increased VTA BDNF expression in rats with non-manipulated VTA MOR expression, while VTA MOR knockdown prevented stress-induced expression of VTA BDNF. Taken together, these results suggest that upregulation of VTA MOR is necessary for the behavioral and biochemical changes induced by social defeat stress. Elucidating VTA MOR regulation of stress effects on the mesolimbic system may provide new therapeutic targets for treating stress-induced vulnerability to substance abuse. PMID:25446676

  11. Diaphragm Muscle Weakness Following Acute Sustained Hypoxic Stress in the Mouse Is Prevented by Pretreatment with N-Acetyl Cysteine

    Directory of Open Access Journals (Sweden)

    Andrew J. O’Leary

    2018-01-01

    Full Text Available Oxygen deficit (hypoxia is a major feature of cardiorespiratory diseases characterized by diaphragm dysfunction, yet the putative role of hypoxic stress as a driver of diaphragm dysfunction is understudied. We explored the cellular and functional consequences of sustained hypoxic stress in a mouse model. Adult male mice were exposed to 8 hours of normoxia, or hypoxia (FiO2 = 0.10 with or without antioxidant pretreatment (N-acetyl cysteine, 200 mg/kg i.p.. Ventilation and metabolism were measured. Diaphragm muscle contractile function, myofibre size and distribution, gene expression, protein signalling cascades, and oxidative stress (TBARS were determined. Hypoxia caused pronounced diaphragm muscle weakness, unrelated to increased respiratory muscle work. Hypoxia increased diaphragm HIF-1α protein content and activated MAPK, mTOR, Akt, and FoxO3a signalling pathways, largely favouring protein synthesis. Hypoxia increased diaphragm lipid peroxidation, indicative of oxidative stress. FoxO3 and MuRF-1 gene expression were increased. Diaphragm 20S proteasome activity and muscle fibre size and distribution were unaffected by acute hypoxia. Pretreatment with N-acetyl cysteine substantially enhanced cell survival signalling, prevented hypoxia-induced diaphragm oxidative stress, and prevented hypoxia-induced diaphragm dysfunction. Hypoxia is a potent driver of diaphragm weakness, causing myofibre dysfunction without attendant atrophy. N-acetyl cysteine protects the hypoxic diaphragm and may have application as a potential adjunctive therapy.

  12. Ganoderma Triterpenoids Exert Antiatherogenic Effects in Mice by Alleviating Disturbed Flow-Induced Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Pei-Ling Hsu

    2018-01-01

    Full Text Available Ganoderma mushrooms, used in traditional Chinese medicine to promote health and longevity, have become widely accepted as herbal supplements. Ganoderma lucidum (GL, a commonly seen ganoderma species, is commercially cultivated under controlled conditions for more consistent chemical composition. The medicinal properties of GL are attributable to its antioxidant and anti-inflammatory activities. We intended to assess the effect of GL in atherosclerosis, an arterial condition associated with chronic oxidative stress and inflammation, using a carotid-artery-ligation mouse model. Flow turbulence created in the ligated artery induces oxidative stress and neointimal hyperplasia, a feature of early atherogenesis. Daily oral GL prevented neointimal thickening 2 weeks after ligation. Moreover, the ganoderma triterpenoid (GT crude extract isolated from GL abolished ligation-induced neointima formation. Mechanistically, endothelial dysfunction was observed 3 days after ligation before any structural changes could be detected. GTs alleviated the oxidative stress and restored the atheroresistent status of endothelium by inhibiting the induction of a series of atherogenic factors, including endothelin-1, von Willebrand factor, and monocyte chemoattractant protein-1 after 3-day ligation. The anti-inflammatory activity of GTs was tested in cultured human umbilical vein endothelial cells (HUVECs exposed to disturbed flow in an in vitro perfusion system. GTs abolished the induction of proinflammatory VCAM-1, TNF-α, and IL-6 by oscillatory shear stress. Moreover, the antioxidant activity of GTs was tested in HUVECs against the insult of H2O2. GTs dissipated the cellular superoxide accumulation imposed by H2O2, thereby mitigating H2O2-induced cell damage and proatherogenic response. Our results revealed the atheroprotective properties of ganoderma mushrooms and identified triterpenoids as the critical constituents for those effects. GTs prevent atherogenesis by

  13. Age-related effects of chronic restraint stress on ethanol drinking, ethanol-induced sedation, and on basal and stress-induced anxiety response.

    Science.gov (United States)

    Fernández, Macarena Soledad; Fabio, María Carolina; Miranda-Morales, Roberto Sebastián; Virgolini, Miriam B; De Giovanni, Laura N; Hansen, Cristian; Wille-Bille, Aranza; Nizhnikov, Michael E; Spear, Linda P; Pautassi, Ricardo Marcos

    2016-03-01

    Adolescents are sensitive to the anxiolytic effect of ethanol, and evidence suggests that they may be more sensitive to stress than adults. Relatively little is known, however, about age-related differences in stress modulation of ethanol drinking or stress modulation of ethanol-induced sedation and hypnosis. We observed that chronic restraint stress transiently exacerbated free-choice ethanol drinking in adolescent, but not in adult, rats. Restraint stress altered exploration patterns of a light-dark box apparatus in adolescents and adults. Stressed animals spent significantly more time in the white area of the maze and made significantly more transfers between compartments than their non-stressed peers. Behavioral response to acute stress, on the other hand, was modulated by prior restraint stress only in adults. Adolescents, unlike adults, exhibited ethanol-induced motor stimulation in an open field. Stress increased the duration of loss of the righting reflex after a high ethanol dose, yet this effect was similar at both ages. Ethanol-induced sleep time was much higher in adult than in adolescent rats, yet stress diminished ethanol-induced sleep time only in adults. The study indicates age-related differences that may increase the risk for initiation and escalation in alcohol drinking. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Characteristics of human hypo- and hyperresponders to dietary cholesterol.

    Science.gov (United States)

    Katan, M B; Beynen, A C

    1987-03-01

    The characteristics of people whose serum cholesterol level is unusually susceptible to consumption of cholesterol were investigated. Thirty-two volunteers from the general population of Wageningen, the Netherlands, each participated in three controlled dietary trials in 1982. A low-cholesterol diet was fed during the first half and a high-cholesterol diet during the second half of each trial, and the change (response) of serum cholesterol was measured. The responses in the three trials were averaged to give each subject's mean responsiveness. Fecal excretion of cholesterol and its metabolites were measured in the second trial, and body cholesterol synthesis was calculated. Responsiveness showed a positive correlation with serum high density lipoprotein2 (HDL2) cholesterol (r = 0.41, p less than 0.05) and with serum total cholesterol level on a high-cholesterol diet (r = 0.31, p = 0.09). A negative relation was found with habitual cholesterol consumption (r = -0.62, p less than 0.01), with body mass index (r = -0.50, p less than 0.01), and with the rate of endogenous cholesterol synthesis (r = -0.40, p less than 0.05), but not with the reaction of endogenous cholesterol synthesis rate to an increased intake of cholesterol. No relation was found with age, sex, total caloric needs, or the ratio of primary to secondary fecal steroids. Upon multiple regression analysis, only habitual cholesterol intake and serum total and HDL2 cholesterol levels contributed significantly to the explanation of variance in responsiveness. Thus, a low habitual cholesterol intake, a high serum HDL2 cholesterol level, or a low body weight do not make one less susceptible to dietary cholesterol-induced hypercholesterolemia.

  15. Sirtuin1 and autophagy protect cells from fluoride-induced cell stress

    Science.gov (United States)

    Suzuki, Maiko; Bartlett, John D.

    2014-01-01

    Sirtuin1 (SIRT1) is an (NAD+)-dependent deacetylase functioning in the regulation of metabolism, cell survival and organismal lifespan. Active SIRT1 regulates autophagy during cell stress, including calorie restriction, endoplasmic reticulum stress and oxidative stress. Previously, we reported that fluoride induces endoplasmic reticulum (ER) stress in ameloblasts responsible for enamel formation, suggesting that ER-stress plays a role in dental fluorosis. However, the molecular mechanism of how cells respond to fluoride-induced cell stress is unclear. Here, we demonstrate that fluoride activates SIRT1 and initiates autophagy to protect cells from fluoride exposure. Fluoride treatment of ameloblast-derived cells (LS8) significantly increased Sirt1 expression and induced SIRT1 phosphorylation resulting in the augmentation of SIRT1 deacetylase activity. To demonstrate that fluoride exposure initiates autophagy, we characterized the expression of autophagy related genes (Atg); Atg5, Atg7 and Atg8/LC3 and showed that both their transcript and protein levels were significantly increased following fluoride treatment. To confirm that SIRT1 plays a protective role in fluoride toxicity, we used resveratrol (RES) to augmented SIRT1 activity in fluoride treated LS8 cells. RES increased autophagy, inhibited apoptosis, and decreased fluoride cytotoxicity. Rats treated with fluoride (0, 50 and 100 ppm) in drinking water for 6 weeks had significantly elevated expression levels of Sirt1, Atg5, Atg7 and Atg8/LC3 in their maturation stage enamel organs. Increased protein levels of p-SIRT1, ATG5 and ATG8/LC3 were present in fluoride-treated rat maturation stage ameloblasts. Therefore, the SIRT1/autophagy pathway may play a critical role as a protective response to help prevent dental fluorosis. PMID:24296261

  16. Sirtuin1 and autophagy protect cells from fluoride-induced cell stress.

    Science.gov (United States)

    Suzuki, Maiko; Bartlett, John D

    2014-02-01

    Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase functioning in the regulation of metabolism, cell survival and organismal lifespan. Active SIRT1 regulates autophagy during cell stress, including calorie restriction, endoplasmic reticulum (ER) stress and oxidative stress. Previously, we reported that fluoride induces ER-stress in ameloblasts responsible for enamel formation, suggesting that ER-stress plays a role in dental fluorosis. However, the molecular mechanism of how cells respond to fluoride-induced cell stress is unclear. Here, we demonstrate that fluoride activates SIRT1 and initiates autophagy to protect cells from fluoride exposure. Fluoride treatment of ameloblast-derived cells (LS8) significantly increased Sirt1 expression and induced SIRT1 phosphorylation resulting in the augmentation of SIRT1 deacetylase activity. To demonstrate that fluoride exposure initiates autophagy, we characterized the expression of autophagy related genes (Atg); Atg5, Atg7 and Atg8/LC3 and showed that both their transcript and protein levels were significantly increased following fluoride treatment. To confirm that SIRT1 plays a protective role in fluoride toxicity, we used resveratrol (RES) to augment SIRT1 activity in fluoride treated LS8 cells. RES increased autophagy, inhibited apoptosis, and decreased fluoride cytotoxicity. Rats treated with fluoride (0, 50, 100 and 125ppm) in drinking water for 6weeks had significantly elevated expression levels of Sirt1, Atg5, Atg7 and Atg8/LC3 in their maturation stage enamel organs. Increased protein levels of p-SIRT1, ATG5 and ATG8/LC3 were present in fluoride-treated rat maturation stage ameloblasts. Therefore, the SIRT1/autophagy pathway may play a critical role as a protective response to help prevent dental fluorosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Inhibitory effects of myricitrin on oxidative stress-induced endothelial damage and early atherosclerosis in ApoE −/− mice

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Gui-bo; Qin, Meng [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, 100193, Beijing (China); Ye, Jing-xue [Jilin Agricultural University, No. 2888, Xincheng Street, Changchun, 130118 Jilin (China); Pan, Rui-le; Meng, Xiang-bao; Wang, Min; Luo, Yun; Li, Zong-yang [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, 100193, Beijing (China); Wang, Hong-wei, E-mail: hwang@nju.edu.cn [Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210093 (China); Sun, Xiao-bo, E-mail: sunsubmit@163.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, 100193, Beijing (China)

    2013-08-15

    Atherosclerosis (AS) is a state of heightened oxidative stress characterized by lipid and protein oxidation in vascular walls. Oxidative stress-induced vascular endothelial cell (VEC) injury is a major factor in the pathogenesis of AS. Myricitrin, a natural flavonoid isolated from the root bark of Myrica cerifera, was recently found to have a strong antioxidative effect. However, its use for treating cardiovascular diseases, especially AS is still unreported. Consequently, we evaluated the cytoprotective effect of myricitrin on AS by assessing oxidative stress-induced VEC damage. The in vivo study using an ApoE −/− mouse model of AS demonstrated that myricitrin treatment protects against VEC damage and inhibits early AS plaque formation. This effect is associated with the antioxidative effect of myricitrin, as observed in a hydrogen peroxide (H{sub 2}O{sub 2})-induced rat model of artery endothelial injury and primary cultured human VECs. Myricitrin treatment also prevents and attenuates H{sub 2}O{sub 2}-induced endothelial injury. Further investigation of the cytoprotective effects of myricitrin demonstrated that myricitrin exerts its function by scavenging for reactive oxygen species, as well as reducing lipid peroxidation, blocking NO release, and maintaining mitochondrial transmembrane potential. Myricitrin treatment also significantly decreased H{sub 2}O{sub 2}-induced apoptosis in VECs, which was associated with significant inhibition of p53 gene expression, activation of caspase-3 and the MAPK signaling pathway, and alteration of the patterns of pro-apoptotic and anti-apoptotic gene expression. The resulting significantly increased bcl-2/bax ratio indicates that myricitrin may prevent the apoptosis induced by oxidative stress injury. - Highlights: • Myricitrin prevents early atherosclerosis in ApoE−/− mice. • Myricitrin protects endothelial cell from H{sub 2}O{sub 2} induced injury in rat and HUVECs. • Myricitrin enhanced NO release and up

  18. Preventing hepatocyte oxidative stress cytotoxicity with Mangifera indica L. extract (Vimang).

    Science.gov (United States)

    Remirez, Diadelis; Tafazoli, Shahrzad; Delgado, Rene; Harandi, Asghar A; O'Brien, Peter J

    2005-01-01

    Vimang is an aqueous extract of Mangifera indica used in Cuba to improve the quality of life in patients suffering from inflammatory diseases. In the present study we evaluated the effects of Vimang at preventing reactive oxygen species (ROS) formation and lipid peroxidation in intact isolated rat hepatocytes. Vimang at 20, 50 and 100 microg/ml inhibited hepatocyte ROS formation induced by glucose-glucose oxidase. Hepatocyte cytotoxicity and lipid peroxidation induced by cumene hydroperoxide was also inhibited by Vimang in a dose and time dependent manner at the same concentration. Vimang also inhibited superoxide radical formation by xanthine oxidase and hypoxanthine. The superoxide radical scavenging and antioxidant activity of the Vimang extract was likely related to its gallates, catechins and mangiferin content. To our knowledge, this is the first report of cytoprotective antioxidant effects of Vimang in cellular oxidative stress models.

  19. O-hexadecyl-dextran entrapped berberine nanoparticles abrogate high glucose stress induced apoptosis in primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Radhika Kapoor

    Full Text Available Nanotized phytochemicals are being explored by researchers for promoting their uptake and effectiveness at lower concentrations. In this study, O-hexadecyl-dextran entrapped berberine chloride nanoparticles (BC-HDD NPs were prepared, and evaluated for their cytoprotective efficacy in high glucose stressed primary hepatocytes and the results obtained compared with bulk berberine chloride (BBR treatment. The nanotized formulation treated primary hepatocytes that were exposed to high glucose (40 mM, showed increased viability compared to the bulk BBR treated cells. BC-HDD NPs reduced the ROS generation by ∼ 3.5 fold during co-treatment, prevented GSH depletion by ∼ 1.6 fold, reduced NO formation by ∼ 5 fold and significantly prevented decline in SOD activity in stressed cells. Lipid peroxidation was also prevented by ∼ 1.9 fold in the presence of these NPs confirming the antioxidant capacity of the formulation. High glucose stress increased Bax/Bcl2 ratio followed by mitochondrial depolarization and activation of caspase-9/-3 confirming involvement of mitochondrial pathway of apoptosis in the exposed cells. Co- and post-treatment of BC-HDD NPs prevented depolarization of mitochondrial membrane, reduced Bax/Bcl2 ratio and prevented externalization of phosphatidyl-serine confirming their anti-apoptotic capacity in those cells. Sub-G1 phase apparent in high glucose stressed cells was not seen in BC-HDD NPs treated cells. The present study reveals that BC-HDD NPs at ∼ 20 fold lower concentration are as effective as BBR in preventing high glucose induced oxidative stress, mitochondrial depolarization and downstream events of apoptotic cell death.

  20. Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway

    International Nuclear Information System (INIS)

    Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min; Xing, Mingyou; Liu, Liegang; Yao, Ping

    2013-01-01

    Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0 g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100 mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8 mg/kg for mice or 20 μmol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. - Highlights: • CO alleviated ethanol-derived liver oxidative and inflammatory stress in mice. • CO eased ethanol and inflammatory factor-induced oxidative damage in hepatocytes. • The p38 MAPK is a key signaling mechanism for the protective function of CO in ALD

  1. Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Xing, Mingyou [Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Liu, Liegang [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Yao, Ping, E-mail: yaoping@mails.tjmu.edu.cn [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China)

    2013-11-15

    Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0 g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100 mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8 mg/kg for mice or 20 μmol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. - Highlights: • CO alleviated ethanol-derived liver oxidative and inflammatory stress in mice. • CO eased ethanol and inflammatory factor-induced oxidative damage in hepatocytes. • The p38 MAPK is a key signaling mechanism for the protective function of CO in ALD.

  2. AMPK activation protects cells from oxidative stress-induced senescence via autophagic flux restoration and intracellular NAD(+) elevation.

    Science.gov (United States)

    Han, Xiaojuan; Tai, Haoran; Wang, Xiaobo; Wang, Zhe; Zhou, Jiao; Wei, Xiawei; Ding, Yi; Gong, Hui; Mo, Chunfen; Zhang, Jie; Qin, Jianqiong; Ma, Yuanji; Huang, Ning; Xiang, Rong; Xiao, Hengyi

    2016-06-01

    AMPK activation is beneficial for cellular homeostasis and senescence prevention. However, the molecular events involved in AMPK activation are not well defined. In this study, we addressed the mechanism underlying the protective effect of AMPK on oxidative stress-induced senescence. The results showed that AMPK was inactivated in senescent cells. However, pharmacological activation of AMPK by metformin and berberine significantly prevented the development of senescence and, accordingly, inhibition of AMPK by Compound C was accelerated. Importantly, AMPK activation prevented hydrogen peroxide-induced impairment of the autophagic flux in senescent cells, evidenced by the decreased p62 degradation, GFP-RFP-LC3 cancellation, and activity of lysosomal hydrolases. We also found that AMPK activation restored the NAD(+) levels in the senescent cells via a mechanism involving mostly the salvage pathway for NAD(+) synthesis. In addition, the mechanistic relationship of autophagic flux and NAD(+) synthesis and the involvement of mTOR and Sirt1 activities were assessed. In summary, our results suggest that AMPK prevents oxidative stress-induced senescence by improving autophagic flux and NAD(+) homeostasis. This study provides a new insight for exploring the mechanisms of aging, autophagy and NAD(+) homeostasis, and it is also valuable in the development of innovative strategies to combat aging. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  3. Plasma membrane cholesterol level and agonist-induced internalization of δ-opioid receptors; colocalization study with intracellular membrane markers of Rab family.

    Science.gov (United States)

    Brejchova, Jana; Vosahlikova, Miroslava; Roubalova, Lenka; Parenti, Marco; Mauri, Mario; Chernyavskiy, Oleksandr; Svoboda, Petr

    2016-08-01

    Decrease of cholesterol level in plasma membrane of living HEK293 cells transiently expressing FLAG-δ-OR by β-cyclodextrin (β-CDX) resulted in a slight internalization of δ-OR. Massive internalization of δ-OR induced by specific agonist DADLE was diminished in cholesterol-depleted cells. These results suggest that agonist-induced internalization of δ-OR, which has been traditionally attributed exclusively to clathrin-mediated pathway, proceeds at least partially via membrane domains. Identification of internalized pools of FLAG-δ-OR by colocalization studies with proteins of Rab family indicated the decreased presence of receptors in early endosomes (Rab5), late endosomes and lysosomes (Rab7) and fast recycling vesicles (Rab4). Slow type of recycling (Rab11) was unchanged by cholesterol depletion. As expected, agonist-induced internalization of oxytocin receptors was totally suppressed in β-CDX-treated cells. Determination of average fluorescence lifetime of TMA-DPH, the polar derivative of hydrophobic membrane probe diphenylhexatriene, in live cells by FLIM indicated a significant alteration of the overall PM structure which may be interpreted as an increased "water-accessible space" within PM area. Data obtained by studies of HEK293 cells transiently expressing FLAG-δ-OR by "antibody feeding" method were extended by analysis of the effect of cholesterol depletion on distribution of FLAG-δ-OR in sucrose density gradients prepared from HEK293 cells stably expressing FLAG-δ-OR. Major part of FLAG-δ-OR was co-localized with plasma membrane marker Na,K-ATPase and β-CDX treatment resulted in shift of PM fragments containing both FLAG-δ-OR and Na,K-ATPase to higher density. Thus, the decrease in content of the major lipid constituent of PM resulted in increased density of resulting PM fragments.

  4. Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10

    International Nuclear Information System (INIS)

    McCarthy, S.; Somayajulu, M.; Sikorska, M.; Borowy-Borowski, H.; Pandey, S.

    2004-01-01

    Neuronal cell death induced by oxidative stress is correlated with numerous neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. The causes of sporadic forms of age-related neurodegenerative diseases are still unknown. Recently, a correlation between paraquat exposure and neurodegenerative diseases has been observed. Paraquat, a nonselective herbicide, was once widely used in North America and is still routinely used in Taiwan. We have used differentiated Human Neuroblastoma (SHSY-5Y) cells as an in vitro model to study the mechanism of cell death induced by paraquat. We observed that paraquat-induced oxidative stress in differentiated SHSY-5Y cells as indicated by an increase in the production of cellular reactive oxygen species (ROS). Furthermore, apoptosis was evident as indicated by cellular and nuclear morphology and DNA fragmentation. Interestingly, pretreatment of SHSY-5Y cells with water-soluble Coenzyme Q 10 (CoQ 10 ) before paraquat exposure inhibited ROS generation. Pretreatment with CoQ 10 also significantly reduced the number of apoptotic cells and DNA fragmentation. We also analyzed the effect of paraquat and CoQ 10 on isolated mitochondria. Our results indicated that treatment with paraquat induced the generation of ROS from isolated mitochondria and depolarization of the inner mitochondrial membrane. Pretreatment with CoQ 10 was able to inhibit ROS generation from isolated mitochondria as well as the collapse of mitochondrial membrane potential. Our results indicate that water-soluble CoQ 10 can prevent oxidative stress and neuronal damage induced by paraquat and therefore, can be used for the prevention and therapy of neurodegenerative diseases caused by environmental toxins

  5. A multiple case study approach to work stress prevention in Europe

    NARCIS (Netherlands)

    Kompier, M.A.J.; Cooper, C.L.; Geurts, S.A.E.; Cooper, C.L.

    2013-01-01

    Work stress has become a major issue among European employees. The current practice of its prevention seems disappointing, as work stress prevention programmes are predominantly reactive and biased to the individual. The lack of organization-level intervention studies is a barrier to progress in

  6. A multiple case study approach to work stress prevention in Europe

    NARCIS (Netherlands)

    Kompier, M.A.J.; Cooper, C.L.; Geurts, S.A.E.

    2000-01-01

    Work stress has become a major issue among European employees. The current practice of its prevention seems disappointing, as work stress prevention programmes are predominantly reactive and biased to the individual. The lack of organization-level intervention studies is a barrier to progress in

  7. The relationship between cholesterol and cognitive function is homocysteine-dependent

    Directory of Open Access Journals (Sweden)

    Cheng YB

    2014-10-01

    Full Text Available Yibin Cheng,1 Yinlong Jin,1 Frederick W Unverzagt,2 Liqin Su,1 Lili Yang,3 Feng Ma,1 Ann M Hake,4,5 Carla Kettler,3 Chen Chen,1 Jingyi Liu,1 Jianchao Bian,6 Ping Li,7 Jill R Murrell,8 Hugh C Hendrie,2,9,10 Sujuan Gao3 1Institute for Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Psychiatry, 3Department of Biostatistics, 4Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA; 5Eli Lilly and Company, Indianapolis, Indiana, USA; 6Shandong Institute for Prevention and Treatment of Endemic Disease in China, Jinan, People’s Republic of China; 7Sichuan Provincial Center for Disease Control and Prevention in China, Chengdu, People’s Republic of China; 8Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 9Indiana University Center for Aging Research, 10Regenstrief Institute, Inc., Indianapolis, Indiana, USA Introduction: Previous studies have identified hyperlipidemia as a potential risk factor for dementia and Alzheimer’s disease. However, studies on cholesterol measured in late-life and cognitive function have been inconsistent. Few studies have explored nonlinear relationships or considered interactions with other biomarker measures.Methods: A cross-sectional sample of 1,889 participants from four rural counties in the People’s Republic of China was included in this analysis. Serum total cholesterol, high-density lipoprotein, triglycerides, and homocysteine levels were measured in fasting blood samples. A composite cognitive score was derived based on nine standardized cognitive test scores. Analysis of covariance models were used to investigate the association between biomarker measures and the composite cognitive scores.Results: There was a significant interaction between the homocysteine quartile group and the cholesterol quartile group on cognitive scores (P=0

  8. Agmatine ameliorates atherosclerosis progression and endothelial dysfunction in high cholesterol-fed rabbits.

    Science.gov (United States)

    El-Awady, Mohammed S; Suddek, Ghada M

    2014-06-01

    The aim of this work was to explore possible effects of agmatine, an endogenous inhibitor of inducible nitric oxide synthase (iNOS), against hypercholesterolemia-induced lipid profile changes and endothelial dysfunction. Hypercholesterolemia was induced by feeding rabbits with a high-cholesterol diet (HCD, 0.5%) for 8 weeks. Another HCD-fed group was orally administered agmatine (10 mg/kg/day) during weeks 5 through 8. Serum lipid profile, malondialdehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) were determined. Aorta was isolated to analyse vascular reactivity, atherosclerotic lesions and intima/media (I/M) ratio. HCD induced a significant increase in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). Agmatine administration significantly decreased HCD-induced elevations in serum TC and LDL-C, MDA, LDH and NO while significantly increased HDL-C levels. Additionally, agmatine significantly protected against HCD-induced attenuation of rabbit aortic endothelium-dependent relaxation to acetylcholine. HCD and agmatine did not significantly influence aortic endothelium-independent relaxation to sodium nitroprusside. Moreover, agmatine significantly reduced the elevation in aortic atherosclerotic lesion area and I/M ratio. This study is the first to reveal that agmatine has the ability to ameliorate hypercholesterolemia-induced lipemic-oxidative and endothelial function injuries possibly by its antioxidant potential and/or iNOS inhibition. © 2014 Royal Pharmaceutical Society.

  9. Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet.

    Science.gov (United States)

    Leite, Jose O; DeOgburn, Ryan; Ratliff, Joseph; Su, Randy; Smyth, Joan A; Volek, Jeff S; McGrane, Mary M; Dardik, Alan; Fernandez, Maria Luz

    2010-04-01

    Low-carbohydrate diets (LCD) efficiently induce weight loss and favorably affect plasma lipids, however, the effect of LCD on atherosclerosis is still argued. To evaluate the effect of LCD on the prevention of atherosclerosis. Twenty guinea pigs were fed either a LCD or a low-fat diet (LFD) in combination with high-cholesterol (0.25g/100g) for 12 weeks. The percentage energy of macronutrient distribution was 10:65:25 for carbohydrate:fat:protein for the LCD, and 55:20:25 for the LFD. Plasma lipids were measured using colorimetric assays. Plasma and aortic oxidized (oxLDL) were quantified using ELISA methods. Inflammatory cytokines were measured in aortic homogenates using an immunoassay. H&E stained sections of aortic sinus and Schultz stained sections of carotid arteries were examined. LDL cholesterol was lower in the LCD compared to the LFD group (71.9+/-34.8 vs. 81.7+/-26.9mg/dL; p=0.039). Aortic cholesterol was also lower in the LCD (4.98+/-1.3mg/g) compared to the LFD group (6.68+/-2.0mg/g); p<0.05. The Schultz staining method confirmed less aortic cholesterol accumulation in the LCD group. Plasma oxLDL did not differ between groups, however, aortic oxLDL was 61% lower in the LCD compared to the LFD group (p=0.045). There was a positive correlation (r=0.63, p=0.03) between oxLDL and cholesterol concentration in the aorta of LFD group, which was not observed in LCD group (r=-0.05, p=0.96). Inflammatory markers were reduced in guinea pigs from the LCD group (p<0.05) and they were correlated with the decreases in oxLDL in aorta. These results suggest that LCD not only decreases lipid deposition, but also prevents the accumulation of oxLDL and reduces inflammatory cytokines within the arterial wall and may prevent atherosclerosis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  10. What's Cholesterol?

    Science.gov (United States)

    ... LDL. Most cholesterol is LDL (low-density lipoprotein) cholesterol. LDL cholesterol is more likely to clog blood vessels because ... Here's a way to remember the difference: the LDL cholesterol is the bad kind, so call it "lousy" ...

  11. Increasing fatty acid oxidation remodels the hypothalamic neurometabolome to mitigate stress and inflammation.

    Directory of Open Access Journals (Sweden)

    Joseph W McFadden

    Full Text Available Modification of hypothalamic fatty acid (FA metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1 and fatty acid oxidation (FAOx, exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS, and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism.

  12. A study on anti-stress property of Nardostachys jatamamsi on stress induced Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Shilpashree R.

    2011-09-01

    Full Text Available Stress is a feeling that’s created when we react to particular events. It s the body’s way of rising to a challenge and preparing to meet a tough situation with focus, strength, stamina, and heightened alertness. As a result of the stress immune system can be suppressed by chronic stress opening to increased infections and increasing the risk of autoimmune diseases. So one has to learn away to overcome stress. Here is an attempt made to overcome the stress induced in Drosophila melanogaster a model organism, in this study. Methotrexate is used to induce the stress at different concentration taking different group of flies and a Nardostachys jatamamsi plant extract having antistress property is used to relieve the stress induced. This stress relieve measured by the various stress related enzymes like catalase and Superoxide dismutase by this antistress property of the plant Nardostachys jatamamsi was shown.

  13. Mitochondrial control of cell death induced by hyperosmotic stress.

    Science.gov (United States)

    Criollo, Alfredo; Galluzzi, Lorenzo; Maiuri, M Chiara; Tasdemir, Ezgi; Lavandero, Sergio; Kroemer, Guido

    2007-01-01

    HeLa and HCT116 cells respond differentially to sorbitol, an osmolyte able to induce hypertonic stress. In these models, sorbitol promoted the phenotypic manifestations of early apoptosis followed by complete loss of viability in a time-, dose-, and cell type-specific fashion, by eliciting distinct yet partially overlapping molecular pathways. In HCT116 but not in HeLa cells, sorbitol caused the mitochondrial release of the caspase-independent death effector AIF, whereas in both cell lines cytochrome c was retained in mitochondria. Despite cytochrome c retention, HeLa cells exhibited the progressive activation of caspase-3, presumably due to the prior activation of caspase-8. Accordingly, caspase inhibition prevented sorbitol-induced killing in HeLa, but only partially in HCT116 cells. Both the knock-out of Bax in HCT116 cells and the knock-down of Bax in A549 cells by RNA interference reduced the AIF release and/or the mitochondrial alterations. While the knock-down of Bcl-2/Bcl-X(L) sensitized to sorbitol-induced killing, overexpression of a Bcl-2 variant that specifically localizes to mitochondria (but not of the wild-type nor of a endoplasmic reticulum-targeted form) strongly inhibited sorbitol effects. Thus, hyperosmotic stress kills cells by triggering different molecular pathways, which converge at mitochondria where pro- and anti-apoptotic members of the Bcl-2 family exert their control.

  14. Membrane cholesterol mediates the cellular effects of monolayer graphene substrates.

    Science.gov (United States)

    Kitko, Kristina E; Hong, Tu; Lazarenko, Roman M; Ying, Da; Xu, Ya-Qiong; Zhang, Qi

    2018-02-23

    Graphene possesses extraordinary properties that promise great potential in biomedicine. However, fully leveraging these properties requires close contact with the cell surface, raising the concern of unexpected biological consequences. Computational models have demonstrated that graphene preferentially interacts with cholesterol, a multifunctional lipid unique to eukaryotic membranes. Here we demonstrate an interaction between graphene and cholesterol. We find that graphene increases cell membrane cholesterol and potentiates neurotransmission, which is mediated by increases in the number, release probability, and recycling rate of synaptic vesicles. In fibroblasts grown on graphene, we also find an increase in cholesterol, which promotes the activation of P2Y receptors, a family of receptor regulated by cholesterol. In both cases, direct manipulation of cholesterol levels elucidates that a graphene-induced cholesterol increase underlies the observed potentiation of each cell signaling pathway. These findings identify cholesterol as a mediator of graphene's cellular effects, providing insight into the biological impact of graphene.

  15. Markers of Oxidative Stress in Dogs with Myxomatous Mitral Valve Disease are Influenced by Sex, Neuter Status, and Serum Cholesterol Concentration

    DEFF Research Database (Denmark)

    Reimann, M. J.; Haggstrom, J.; Moller, J. E.

    2017-01-01

    Background Cardiovascular disease has been associated with oxidative stress, which has been suggested to contribute to myocardial remodeling in human patients. Little is known about the relationship between myxomatous mitral valve disease (MMVD) and oxidative stress in dogs. Objective To determin...... with clinical stage of MMVD. Conclusions In conclusion, markers of oxidative stress are associated with sex, BCS, neuter status, and cholesterol. The results cannot confirm a relationship between oxidative stress and clinical stage of the disease in dogs with MMVD.......Background Cardiovascular disease has been associated with oxidative stress, which has been suggested to contribute to myocardial remodeling in human patients. Little is known about the relationship between myxomatous mitral valve disease (MMVD) and oxidative stress in dogs. Objective To determine...... whether clinical stage of MMVD is associated with changes in the plasma concentrations of certain markers of oxidative stress in clinically healthy dogs and dogs with MMVD. Animals Seventy five privately owned dogs: 59 cavalier King Charles Spaniels (CKCS) with different severities of MMVD and 16 dogs...

  16. Dioscoreophyllum cumminsii (Stapf) Diels leaves halt high-fructose induced metabolic syndrome: Hyperglycemia, insulin resistance, inflammation and oxidative stress.

    Science.gov (United States)

    Ajiboye, T O; Aliyu, H; Tanimu, M A; Muhammad, R M; Ibitoye, O B

    2016-11-04

    Dioscoreophyllum cumminsii is widely used in the management and treatment of diabetes and obesity in Nigeria. This study evaluates the effect of aqueous leaf extract of D. cumminsii on high-fructose diet-induced metabolic syndrome. Seventy male rats were randomized into seven groups. All rats were fed with high-fructose diet for 9 weeks except groups A and C rats, which received control diet. In addition to the diet treatment, groups A and B rats received distilled water for 3 weeks starting from the seventh week of the experimental period. Rats in groups C-F orally received 400, 100, 200 and 400mg/kg body weight of aqueous leaf extract of D. cumminsii respectively, while group G received 300mg/kg bodyweight of metformin for 3 weeks starting from the seventh week. There was significant (phigh-fructose diet-mediated increase in body weight, body mass index, abdominal circumference, blood glucose, insulin, leptin and insulin resistance by aqueous leaf extract of D. cumminsii. Conversely, high-fructose diet-mediated decrease in adiponectin was reversed by the extract. Increased levels of cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, cardiac index and coronary artery index were significantly lowered by the extract, while high-fructose diet mediated decrease in high-density lipoprotein cholesterol was increased by the extract. Tumour necrosis factor-α, interleukin-6 and interleukin-8 levels increased significantly in high-fructose diet-fed rats, which were significantly reversed by the extract. High-fructose mediated-decrease in superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase and glutathione reduced were significantly reversed by aqueous leaf extract of D. cumminsii. Conversely, elevated levels of malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and fragmented DNA were significantly lowered by the

  17. Ion beam induced stress formation and relaxation in germanium

    Energy Technology Data Exchange (ETDEWEB)

    Steinbach, T., E-mail: Tobias.Steinbach@uni-jena.de [Institut für Festkörperphysik, Friedrich-Schiller-Universität Jena, Max-Wien-Platz 1, D-07743 Jena (Germany); Reupert, A.; Schmidt, E.; Wesch, W. [Institut für Festkörperphysik, Friedrich-Schiller-Universität Jena, Max-Wien-Platz 1, D-07743 Jena (Germany)

    2013-07-15

    Ion irradiation of crystalline solids leads not only to defect formation and amorphization but also to mechanical stress. In the past, many investigations in various materials were performed focusing on the ion beam induced damage formation but only several experiments were done to investigate the ion beam induced stress evolution. Especially in microelectronic devices, mechanical stress leads to several unwanted effects like cracking and peeling of surface layers as well as changing physical properties and anomalous diffusion of dopants. To study the stress formation and relaxation process in semiconductors, crystalline and amorphous germanium samples were irradiated with 3 MeV iodine ions at different ion fluence rates. The irradiation induced stress evolution was measured in situ with a laser reflection technique as a function of ion fluence, whereas the damage formation was investigated by means of Rutherford backscattering spectrometry. The investigations show that mechanical stress builds up at low ion fluences as a direct consequence of ion beam induced point defect formation. However, further ion irradiation causes a stress relaxation which is attributed to the accumulation of point defects and therefore the creation of amorphous regions. A constant stress state is reached at high ion fluences if a homogeneous amorphous surface layer was formed and no further ion beam induced phase transition took place. Based on the results, we can conclude that the ion beam induced stress evolution seems to be mainly dominated by the creation and accumulation of irradiation induced structural modification.

  18. Laser-induced stresses versus mechanical stress power measurements during laser ablation of solids

    International Nuclear Information System (INIS)

    Shannon, M.A.; Russo, R.E.

    1995-01-01

    Laser-induced stresses resulting from high-power laser-material interactions have been studied extensively. However, the rate of change in mechanical energy, or stress power, due to laser-induced stresses has only recently been investigated. An unanswered question for monitoring laser-material interactions in the far-field is whether stress power differs from stresses measured, particularly with respect to laser-energy coupling to a solid target. This letter shows experimental acoustic data which demonstrate that stress power measured in the far field of the target shows changes in laser-energy coupling, whereas the stresses measured do not. For the ambient medium above the target, stress power and stress together reflect changes in laser-energy coupling. copyright 1995 American Institute of Physics

  19. Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

    Science.gov (United States)

    Hannaoui, Samia; Shim, Su Yeon; Cheng, Yo Ching; Corda, Erica; Gilch, Sabine

    2014-01-01

    Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI) anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD): whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD. PMID:25419621

  20. Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Samia Hannaoui

    2014-11-01

    Full Text Available Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD: whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD.

  1. Effect of turmeric and curcumin on oxidative stress and antioxidant enzymes in streptozotocin-induced diabetic rat.

    Science.gov (United States)

    Suryanarayana, Palla; Satyanarayana, Alleboena; Balakrishna, Nagalla; Kumar, Putcha Uday; Reddy, Geereddy Bhanuprakash

    2007-12-01

    There is increasing evidence that complications related to diabetes are associated with increased oxidative stress. Curcumin, an active principle of turmeric, has several biological properties, including antioxidant activity. The protective effect of curcumin and turmeric on streptozotocin (STZ)-induced oxidative stress in various tissues of rats was studied. Three-month-old Wistar-NIN rats were made diabetic by injecting STZ (35 mg/kg body weight) intraperitoneally and fed either only the AIN-93 diet or the AIN-93 diet containing 0.002% or 0.01% curcumin or 0.5% turmeric for a period of eight weeks. After eight weeks the levels of oxidative stress parameters and activity of antioxidant enzymes were determined in various tissues. STZ-induced hyperglycemia resulted in increased lipid peroxidation and protein carbonyls in red blood cells and other tissues and altered antioxidant enzyme activities. Interestingly, feeding curcumin and turmeric to the diabetic rats controlled oxidative stress by inhibiting the increase in TBARS and protein carbonyls and reversing altered antioxidant enzyme activities without altering the hyperglycemic state in most of the tissues. Turmeric and curcumin appear to be beneficial in preventing diabetes-induced oxidative stress in rats despite unaltered hyperglycemic status.

  2. Finite element calculation of stress induced heating of superconductors

    International Nuclear Information System (INIS)

    Akin, J.E.; Moazed, A.

    1976-01-01

    This research is concerned with the calculation of the amount of heat generated due to the development of mechanical stresses in superconducting composites. An emperical equation is used to define the amount of stress-induced heat generation per unit volume. The equation relates the maximum applied stress and the experimental measured hysteresis loop of the composite stress-strain diagram. It is utilized in a finite element program to calculate the total stress-induced heat generation for the superconductor. An example analysis of a solenoid indicates that the stress-induced heating can be of the same order of magnitude as eddy current effects

  3. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xiaolin [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China); Li, Qian [Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai (China); Pang, Liewen; Huang, Guoqian; Huang, Jiechun; Shi, Meng; Sun, Xiaotian [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China); Wang, Yiqing [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China)

    2013-11-15

    Highlights: •Arctigenin enhanced cholesterol efflux in oxLDL-loaded THP-1 macrophages. •The expression of ABCA1, ABCG1 and apoE was upregulated in arctigenin-treated cells. •Arctigenin promoted the expression of PPAR-γ and LXR-α. •Inhibition of PPAR-γ or LXR-α reversed arctigenin-mediated biological effects. •Arctigenin promotes cholesterol efflux via activation of PPAR-γ/LXR-α/ABCA1 pathway. -- Abstract: Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α.

  4. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway

    International Nuclear Information System (INIS)

    Xu, Xiaolin; Li, Qian; Pang, Liewen; Huang, Guoqian; Huang, Jiechun; Shi, Meng; Sun, Xiaotian; Wang, Yiqing

    2013-01-01

    Highlights: •Arctigenin enhanced cholesterol efflux in oxLDL-loaded THP-1 macrophages. •The expression of ABCA1, ABCG1 and apoE was upregulated in arctigenin-treated cells. •Arctigenin promoted the expression of PPAR-γ and LXR-α. •Inhibition of PPAR-γ or LXR-α reversed arctigenin-mediated biological effects. •Arctigenin promotes cholesterol efflux via activation of PPAR-γ/LXR-α/ABCA1 pathway. -- Abstract: Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α

  5. Xylitol prevents NEFA-induced insulin resistance in rats

    Science.gov (United States)

    Kishore, P.; Kehlenbrink, S.; Hu, M.; Zhang, K.; Gutierrez-Juarez, R.; Koppaka, S.; El-Maghrabi, M. R.

    2013-01-01

    Aims/hypothesis Increased NEFA levels, characteristic of type 2 diabetes mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced insulin resistance was formerly attributed to decreased glycolysis, it is likely that glucose transport is the rate-limiting defect. Recently, the plant-derived sugar alcohol xylitol has been shown to have favourable metabolic effects in various animal models. Furthermore, its derivative xylulose 5-phosphate may prevent NEFA-induced suppression of glycolysis. We therefore examined whether and how xylitol might prevent NEFA-induced insulin resistance. Methods We examined the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained ~1.5-fold elevations in NEFA levels were induced with Intralipid/heparin infusions during 5 h euglycaemic–hyperinsulinaemic clamp studies in 24 conscious non-diabetic Sprague-Dawley rats, with or without infusion of xylitol. Results Intralipid infusion reduced peripheral glucose uptake by ~25%, predominantly through suppression of glycogen synthesis. Co-infusion of xylitol prevented the NEFA-induced decreases in both glucose uptake and glycogen synthesis. Although glycolysis was increased by xylitol infusion alone, there was minimal NEFA-induced suppression of glycolysis, which was not affected by co-infusion of xylitol. Conclusions/interpretation We conclude that xylitol prevented NEFA-induced insulin resistance, with favourable effects on glycogen synthesis accompanying the improved insulin-mediated glucose uptake. This suggests that this pentose sweetener has beneficial insulin-sensitising effects. PMID:22460760

  6. Preventive effects of β-cryptoxanthin against cadmium-induced oxidative stress in the rat testis

    Directory of Open Access Journals (Sweden)

    Xiao-Ran Liu

    2016-01-01

    Full Text Available β-cryptoxanthin (CRY, a major carotenoid of potential interest for health, is obtained naturally from orange vegetables and fruits. A few research studies have reported that CRY could decrease oxidative stress and germ cell apoptosis. The purpose of this study was to examine the effects of CRY on acute cadmium chloride (CdCl 2 -induced oxidative damage in rat testes. For this study, 24 rats were divided into four groups, one of which serves as a control group that received intraperitoneal (i.p. injections of corn oil and physiological saline. The other rats were i.p. injected with CRY (10 μg kg−1 every 8 h, beginning 8 h before CdCl 2 (2.0 mg kg−1 treatment. The pathological and TUNEL findings revealed that CRY ameliorated the Cd-induced testicular histological changes and germ cell apoptosis in the rats. Furthermore, the Cd-induced decrease in the testicular testosterone (T level was attenuated after CRY administration (P < 0.05. The administration of CRY significantly reversed the Cd-induced increases in the lipid peroxide (LPO and malondialdehyde (MDA levels (P < 0.01. The testicular antioxidants superoxide dismutase (SOD, catalase (CAT and glutathione (GSH were decreased by treatment with Cd alone but were restored by CRY co-treatment. These results demonstrated that the application of CRY can enhance the tolerance of rats to Cd-induced oxidative damage and suggest that it has promised as a pharmacological agent to protect against Cd-induced testicular toxicity.

  7. Dietary saturated fat/cholesterol, but not unsaturated fat or starch, induces C-reactive protein associated early atherosclerosis and ectopic fat deposition in diabetic pigs

    Directory of Open Access Journals (Sweden)

    Serlie Mireille J

    2011-07-01

    Full Text Available Abstract Background Diabetes is thought to accelerate cardiovascular disease depending on the type of diet. This study in diabetic subjects was performed to investigate the metabolic, inflammatory and cardiovascular effects of nutritional components typically present in a Western, Mediterranean or high glycaemic diet. Methods Streptozotocin-diabetic pigs (~45 kg were fed for 10 weeks supplemental (40% of dietary energy saturated fat/cholesterol (SFC, unsaturated fat (UF or starch (S in an eucaloric dietary intervention study. Results Fasting plasma total, LDL and HDL cholesterol concentrations were 3-5 fold higher (p 2 = 0.95. Retroperitoneal fat depot weight (g was intermediate in SFC (260 ± 72, lowest in S (135 ± 51 and highest (p Conclusion Dietary saturated fat/cholesterol induces inflammation, atherosclerosis and ectopic fat deposition whereas an equally high dietary unsaturated fat load does not induce these abnormalities and shows beneficial effects on postprandial glycaemia in diabetic pigs.

  8. Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of gut-liver-adipose tissue axis.

    Science.gov (United States)

    Choi, Youngshim; Abdelmegeed, Mohamed A; Song, Byoung-Joon

    2018-05-01

    Indole-3-carbinol (I3C), found in Brassica family vegetables, exhibits antioxidant, anti-inflammatory, and anti-cancerous properties. Here, we aimed to evaluate the preventive effects of I3C against ethanol (EtOH)-induced liver injury and study the protective mechanism(s) by using the well-established chronic-plus-binge alcohol exposure model. The preventive effects of I3C were evaluated by conducting various histological, biochemical, and real-time PCR analyses in mouse liver, adipose tissue, and colon, since functional alterations of adipose tissue and intestine can also participate in promoting EtOH-induced liver damage. Daily treatment with I3C alleviated EtOH-induced liver injury and hepatocyte apoptosis, but not steatosis, by attenuating elevated oxidative stress, as evidenced by the decreased levels of hepatic lipid peroxidation, hydrogen peroxide, CYP2E1, NADPH-oxidase, and protein acetylation with maintenance of mitochondrial complex I, II, and III protein levels and activities. I3C also restored the hepatic antioxidant capacity by preventing EtOH-induced suppression of glutathione contents and mitochondrial aldehyde dehydrogenase-2 activity. I3C preventive effects were also achieved by attenuating the increased levels of hepatic proinflammatory cytokines, including IL1β, and neutrophil infiltration. I3C also attenuated EtOH-induced gut leakiness with decreased serum endotoxin levels through preventing EtOH-induced oxidative stress, apoptosis of enterocytes, and alteration of tight junction protein claudin-1. Furthermore, I3C alleviated adipose tissue inflammation and decreased free fatty acid release. Collectively, I3C prevented EtOH-induced liver injury via attenuating the damaging effect of ethanol on the gut-liver-adipose tissue axis. Therefore, I3C may also have a high potential for translational research in treating or preventing other types of hepatic injury associated with oxidative stress and inflammation. Copyright © 2017 Elsevier Inc. All

  9. Grape Seed Proanthocyanidin Extract Prevents Ovarian Aging by Inhibiting Oxidative Stress in the Hens

    Directory of Open Access Journals (Sweden)

    Xingting Liu

    2018-01-01

    Full Text Available Oxidative stress is an important inducement in ovarian aging which results in fecundity decline in human and diverse animals. As a potent antioxidant, grape seed proanthocyanidin extract (GSPE was investigated to ameliorate chicken ovarian aging in this study. Firstly, ovarian antioxidant capacity of hens at different ages (90, 150, 280, and 580 days old was compared to elucidate its age-related changes. Subsequently, a D-gal-induced (2.5 mg/mL aging ovarian model was established and the cultured ovarian tissues were treated with GSPE at 5 μg/mL for 72 h to evaluate the putative attenuating effects of GSPE on ovarian aging. Meanwhile, ovaries of D280 (young and D580 (old were treated with GSPE for 72 h in culture to verify the protective effects of GSPE on natural aging ovary. The results showed that GSPE could rescue the antioxidant capacity decline by increasing the antioxidase activities and their gene expression in either D-gal-induced or natural aging ovaries. Moreover, GSPE could maintain the homeostasis between cell proliferation and apoptosis in the D-gal-induced and natural aging ovaries, as well as alleviate D-gal-induced nucleus chromatin condensation in the ovarian granulosa cells. In conclusion, GSPE treatment can effectively prevent the ovarian aging process in hens by reducing oxidative stress.

  10. Exercise training prevents the attenuation of anesthetic pre-conditioning-mediated cardioprotection in diet-induced obese rats.

    Science.gov (United States)

    Li, L; Meng, F; Li, N; Zhang, L; Wang, J; Wang, H; Li, D; Zhang, X; Dong, P; Chen, Y

    2015-01-01

    Obesity abolishes anesthetic pre-conditioning-induced cardioprotection due to impaired reactive oxygen species (ROS)-mediated adenosine monophosphate-activated protein kinase (AMPK) pathway, a consequence of increased basal myocardial oxidative stress. Exercise training has been shown to attenuate obesity-related oxidative stress. This study tests whether exercise training could normalize ROS-mediated AMPK pathway and prevent the attenuation of anesthetic pre-conditioning-induced cardioprotection in obesity. Male Sprague-Dawley rats were divided into lean rats fed with control diet and obese rats fed with high-fat diet. After 4 weeks of feeding, lean and obese rats were assigned to sedentary conditions or treadmill exercise for 8 weeks. There was no difference in infarct size between lean sedentary and obese sedentary rats after 25 min of myocardial ischemia followed by 120 min reperfusion. In lean rats, sevoflurane equally reduced infarct size in lean sedentary and lean exercise-trained rats. Molecular studies revealed that AMPK activity, endothelial nitric oxide synthase, and superoxide production measured at the end of ischemia in lean rats were increased in response to sevoflurane. In obese rats, sevoflurane increased the above molecular parameters and reduced infarct size in obese exercise-trained rats but not in obese sedentary rats. Additional study showed that obese exercise-trained rats had decreased basal oxidative stress than obese sedentary rats. The results indicate that exercise training can prevent the attenuation of anesthetic cardioprotection in obesity. Preventing the attenuation of this strategy may be associated with reduced basal oxidative stress and normalized ROS-mediated AMPK pathway, but the causal relationship remains to be determined. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  11. Aerobic exercise modulation of mental stress-induced responses in cultured endothelial progenitor cells from healthy and metabolic syndrome subjects.

    Science.gov (United States)

    Rocha, Natalia G; Sales, Allan R K; Miranda, Renan L; Silva, Mayra S; Silva, Jemima F R; Silva, Bruno M; Santos, Aline A; Nóbrega, Antonio C L

    2015-02-15

    Numerous studies have demonstrated that exercise acutely prevents the reduction in flow-mediated dilation induced by mental stress in subjects with metabolic syndrome (MetS). However, it is unknown whether a similar effect occurs in endothelial progenitors cells (EPCs). This study investigated whether exercise protects from the deleterious effect of mental stress on cultured EPCs in healthy subjects and those with MetS. Ten healthy subjects (aged 31±2) and ten subjects with MetS (aged 36±2) were enrolled. Subjects underwent a mental stress test, followed immediately by either 40 min of leg cycling or rest across two randomized sessions: mental stress+non-exercise control (MS) and mental stress+exercise (MS+EXE). The Stroop Color-Word Test was used to elicit mental stress. Blood samples were drawn at baseline and following sessions to isolate mononuclear cells. These cells were cultured in fibronectin-coated plates for seven days, and EPCs were identified by immunofluorescence (acLDL(+)/ UEA-I Lectin(+)). All subjects presented similar increases in mean blood pressure and heart rate during the mental stress test (P0.05). The EPC response to MS and MS+EXE was increased in healthy subjects, whereas it was decreased in subjects with MetS (Pexercise session increased EPCs in healthy subjects but did not prevent the EPC reduction induced by mental stress among subjects with MetS. © 2015.

  12. Stress-reducing preventive maintenance model for a unit under stressful environment

    International Nuclear Information System (INIS)

    Park, J.H.; Chang, Woojin; Lie, C.H.

    2012-01-01

    We develop a preventive maintenance (PM) model for a unit operated under stressful environment. The PM model in this paper consists of a failure rate model and two cost models to determine the optimal PM scheduling which minimizes a cost rate. The assumption for the proposed model is that stressful environment accelerates the failure of the unit and periodic maintenances reduce stress from outside. The failure rate model handles the maintenance effect of PM using improvement and stress factors. The cost models are categorized into two failure recognition cases: immediate failure recognition and periodic failure detection. The optimal PM scheduling is obtained by considering the trade-off between the related cost and the lifetime of a unit in our model setting. The practical usage of our proposed model is tested through a numerical example.

  13. Stress- and glucocorticoid-induced priming of neuroinflammatory responses: potential mechanisms of stress-induced vulnerability to drugs of abuse.

    Science.gov (United States)

    Frank, Matthew G; Watkins, Linda R; Maier, Steven F

    2011-06-01

    Stress and stress-induced glucocorticoids (GCs) sensitize drug abuse behavior as well as the neuroinflammatory response to a subsequent pro-inflammatory challenge. Stress also predisposes or sensitizes individuals to develop substance abuse. There is an emerging evidence that glia and glia-derived neuroinflammatory mediators play key roles in the development of drug abuse. Drugs of abuse such as opioids, psychostimulants, and alcohol induce neuroinflammatory mediators such as pro-inflammatory cytokines (e.g. interleukin (IL)-1β), which modulate drug reward, dependence, and tolerance as well as analgesic properties. Drugs of abuse may directly activate microglial and astroglial cells via ligation of Toll-like receptors (TLRs), which mediate the innate immune response to pathogens as well as xenobiotic agents (e.g. drugs of abuse). The present review focuses on understanding the immunologic mechanism(s) whereby stress primes or sensitizes the neuroinflammatory response to drugs of abuse and explores whether stress- and GC-induced sensitization of neuroimmune processes predisposes individuals to drug abuse liability and the role of neuroinflammatory mediators in the development of drug addiction. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Protective Effect of T. violacea Rhizome Extract Against Hypercholesterolemia-Induced Oxidative Stress in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Olorunnisola Sinbad Olorunnisola

    2012-05-01

    Full Text Available The present study examines the effect of methanolic extract of T. violacea rhizomes on high cholesterol (2% diet fed rats (HCD. At the end of 4 weeks, serum total protein, albumin, reduced glutathione (GSH, and markers of oxidative stress viz., catalase (CAT, superoxide dismutase (SOD, thiobarbituric acid reactive substances (TBARS—a marker of lipid peroxidation, glutathione-S-transferase (GST and glutathione peroxidase (GPx in the serum, aorta, liver and heart of HCD and normal rats were assessed and compared. A significant (p < 0.05 elevation in TBARS, and a reduction (p < 0.05 in serum total protein, albumin, GSH and antioxidant enzyme activities was observed in tissues of HCD fed rats compared with the normal group. Co-administration of crude extracts of T. violacea rhizomes protected the liver, heart, serum and aorta against HCD-induced lipid peroxidation in a dose dependant manner. The activities of the extract (500 mg/kg compared favorably with gemfibrozil. The extracts also protected against HCD-induced reduction in serum total protein, GSH and restored the activities of antioxidant tissues (liver, heart and aorta enzymes to near normal values. This result suggested that consumption of T. violacea rhizome may help to protect against hypercholesterolemia- induced oxidative stress diseases in the heart and liver.

  15. Effects of stress on gastrointestinal function: interactions of neural and endocrine systems in mediating stress-induced intestinal dysfunction in rats

    International Nuclear Information System (INIS)

    Williams, C.L.

    1987-01-01

    The etiology of stress-induced intestinal dysfunction is completely unresolved, and the lack of an appropriate animal model has hindered studies of causality. We compared a number of stressors and their resultant effects on intestinal transit, a measure of the propulsive motor activity of the gut, in the rat. We found that the response of the intestine to stress, and the neural systems activated by stress, were dependent on the type and duration of stress, as well as the animal strain, and gender. We developed a model, acute wrapping restraint stress, to fully characterize the effects of stress on intestinal transit. Wrap restraint stress is a nonulcerogenic model in which rats are subjected to acute restraint by wrapping them in a harness of paper tape to restrict, but not prevent movement of the upper body and forelimbs. Transit was evaluated by the geometric center method, in which a radiomarker ( 51 Cr) is instilled directly into the proximal duodenum and proximal colon via a surgically placed intestinal cannula, in fasted, adult female Sprague Dawley rats

  16. Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

    Science.gov (United States)

    Bhattacharya, Sharmila; Hosamani, Ravikumar

    2015-01-01

    Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

  17. Mangifera indica L. extract (Vimang®) reduces plasma and liver cholesterol and leucocyte oxidative stress in hypercholesterolemic LDL receptor deficient mice.

    Science.gov (United States)

    Dorighello, Gabriel G; Inada, Natália M; Paim, Bruno A; Pardo-Andreu, Gilberto L; Vercesi, Anibal E; Oliveira, Helena C F

    2018-06-01

    Cardiovascular diseases are major causes of death worldwide. Beyond the classical cholesterol risk factor, other conditions such as oxidative stress are well documented to promote atherosclerosis. The Mangifera indica L. extract (Vimang®) was reported to present antioxidant and hypocholesterolemic properties. Thus, here we evaluate the effects of Vimang treatment on risk factors of the atherosclerosis prone model of familial hypercholesterolemia, the LDL receptor knockout mice. Mice were treated with Vimang during 2 weeks and were fed a cholesterol-enriched diet during the second week. The Vimang treated mice presented significantly reduced levels of plasma (15%) and liver (20%) cholesterol, increased plasma total antioxidant capacity (10%) and decreased reactive oxygen species (ROS) production by spleen mononuclear cells (50%), P Vimang treated mice. Therefore, in this study we demonstrated that Vimang has protective effects on systemic and tissue-specific risk factors, but it is not sufficient to promote a reduction in the initial steps of atherosclerosis development. In addition, we disclosed a new antioxidant target of Vimang, the spleen mononuclear cells that might be relevant for more advanced stages of atherosclerosis. © 2018 International Federation for Cell Biology.

  18. STRESS INDUCED OBESITY: LESSONS FROM RODENT MODELS OF STRESS

    Directory of Open Access Journals (Sweden)

    Zachary Robert Patterson

    2013-07-01

    Full Text Available Stress is defined as the behavioral and physiological responses generated in the face of, or in anticipation of, a perceived threat. The stress response involves activation of the sympathetic nervous system and recruitment of the hypothalamic-pituitary-adrenal (HPA axis. When an organism encounters a stressor (social, physical, etc., these endogenous stress systems are stimulated in order to generate a fight-or-flight response, and manage the stressful situation. As such, an organism is forced to liberate energy resources in attempt to meet the energetic demands posed by the stressor. A change in the energy homeostatic balance is thus required to exploit an appropriate resource and deliver useable energy to the target muscles and tissues involved in the stress response. Acutely, this change in energy homeostasis and the liberation of energy is considered advantageous, as it is required for the survival of the organism. However, when an organism is subjected to a prolonged stressor, as is the case during chronic stress, a continuous irregularity in energy homeostasis is considered detrimental and may lead to the development of metabolic disturbances such as cardiovascular disease, type II diabetes mellitus and obesity. This concept has been studied extensively using animal models, and the neurobiological underpinnings of stress induced metabolic disorders are beginning to surface. However, different animal models of stress continue to produce divergent metabolic phenotypes wherein some animals become anorexic and loose body mass while others increase food intake and body mass and become vulnerable to the development of metabolic disturbances. It remains unclear exactly what factors associated with stress models can be used to predict the metabolic outcome of the organism. This review will explore a variety of rodent stress models and discuss the elements that influence the metabolic outcome in order to further our understanding of stress-induced

  19. Hyperglycemia-induced diaphragm weakness is mediated by oxidative stress

    Science.gov (United States)

    2014-01-01

    Introduction A major consequence of ICU-acquired weakness (ICUAW) is diaphragm weakness, which prolongs the duration of mechanical ventilation. Hyperglycemia (HG) is a risk factor for ICUAW. However, the mechanisms underlying HG-induced respiratory muscle weakness are not known. Excessive reactive oxygen species (ROS) injure multiple tissues during HG, but only one study suggests that excessive ROS generation may be linked to HG-induced diaphragm weakness. We hypothesized that HG-induced diaphragm dysfunction is mediated by excessive superoxide generation and that administration of a specific superoxide scavenger, polyethylene glycol superoxide dismutase (PEG-SOD), would ameliorate these effects. Methods HG was induced in rats using streptozotocin (60 mg/kg intravenously) and the following groups assessed at two weeks: controls, HG, HG + PEG-SOD (2,000U/kg/d intraperitoneally for seven days), and HG + denatured (dn)PEG-SOD (2000U/kg/d intraperitoneally for seven days). PEG-SOD and dnPEG-SOD were administered on day 8, we measured diaphragm specific force generation in muscle strips, force-pCa relationships in single permeabilized fibers, contractile protein content and indices of oxidative stress. Results HG reduced diaphragm specific force generation, altered single fiber force-pCa relationships, depleted troponin T, and increased oxidative stress. PEG-SOD prevented HG-induced reductions in diaphragm specific force generation (for example 80 Hz force was 26.4 ± 0.9, 15.4 ± 0.9, 24.0 ± 1.5 and 14.9 ± 0.9 N/cm2 for control, HG, HG + PEG-SOD, and HG + dnPEG-SOD groups, respectively, P hyperglycemia-induced diaphragm dysfunction. This new mechanistic information could explain how HG alters diaphragm function during critical illness. PMID:24886999

  20. Biological effects of laser-induced stress waves

    International Nuclear Information System (INIS)

    Doukas, A.; Lee, S.; McAuliffe, D.

    1995-01-01

    Laser-induced stress waves can be generated by one of the following mechanisms: Optical breakdown, ablation or rapid heating of an absorbing medium. These three modes of laser interaction with matter allow the investigation of cellular and tissue responses to stress waves with different characteristics and under different conditions. The most widely studied phenomena are those of the collateral damage seen in photodisruption in the eye and in 193 run ablation of cornea and skin. On the other hand, the therapeutic application of laser-induced stress waves has been limited to the disruption of noncellular material such as renal stones, atheromatous plaque and vitreous strands. The effects of stress waves to cells and tissues can be quite disparate. Stress waves can fracture tissue, damage cells, and increase the permeability of the plasma membrane. The viability of cell cultures exposed to stress waves increases with the peak stress and the number of pulses applied. The rise time of the stress wave also influences the degree of cell injury. In fact, cell viability, as measured by thymidine incorporation, correlates better with the stress gradient than peak stress. Recent studies have also established that stress waves induce a transient increase of the permeability of the plasma membrane in vitro. In addition, if the stress gradient is below the damage threshhold, the cells remain viable. Thus, stress waves can be useful as a means of drug delivery, increasing the intracellular drug concentration and allowing the use of drugs which are impermeable to the cell membrane. The present studies show that it is important to create controllable stress waves. The wavelength tunability and the micropulse structure of the free electron laser is ideal for generating stress waves with independently adjustable parameters, such as rise time, duration and peak stress

  1. Hormonal and molecular effects of restraint stress on formalin-induced pain-like behavior in male and female mice.

    Science.gov (United States)

    Long, Caela C; Sadler, Katelyn E; Kolber, Benedict J

    2016-10-15

    The evolutionary advantages to the suppression of pain during a stressful event (stress-induced analgesia (SIA)) are obvious, yet the reasoning behind sex-differences in the expression of this pain reduction are not. The different ways in which males and females integrate physiological stress responses and descending pain inhibition are unclear. A potential supraspinal modulator of stress-induced analgesia is the central nucleus of the amygdala (CeA). This limbic brain region is involved in both the processing of stress and pain; the CeA is anatomically and molecularly linked to regions of the hypothalamic pituitary adrenal (HPA) axis and descending pain network. The CeA exhibits sex-based differences in response to stress and pain that may differentially induce SIA in males and females. Here, sex-based differences in behavioral and molecular indices of SIA were examined following noxious stimulation. Acute restraint stress in male and female mice was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. Spontaneous pain-like behaviors were measured for 60min following formalin injection and mechanical hypersensitivity was evaluated 120 and 180min post-injection. Restraint stress altered formalin-induced spontaneous behaviors in male and female mice and formalin-induced mechanical hypersensitivity in male mice. To assess molecular indices of SIA, tissue samples from the CeA and blood samples were collected at the 180min time point. Restraint stress prevented formalin-induced increases in extracellular signal regulated kinase 2 (ERK2) phosphorylation in the male CeA, but no changes associated with pERK2 were seen with formalin or restraint in females. Sex differences were also seen in plasma corticosterone concentrations 180min post injection. These results demonstrate sex-based differences in behavioral, molecular, and hormonal indices of acute stress in mice that extend for 180min after stress and noxious stimulation. Copyright

  2. HCV-Induced Oxidative Stress: Battlefield-Winning Strategy

    Directory of Open Access Journals (Sweden)

    Khadija Rebbani

    2016-01-01

    Full Text Available About 150 million people worldwide are chronically infected with hepatitis C virus (HCV. The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24 is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis.

  3. Effects of induced stress on seismic forward modelling and inversion

    Science.gov (United States)

    Tromp, Jeroen; Trampert, Jeannot

    2018-05-01

    We demonstrate how effects of induced stress may be incorporated in seismic modelling and inversion. Our approach is motivated by the accommodation of pre-stress in global seismology. Induced stress modifies both the equation of motion and the constitutive relationship. The theory predicts that induced pressure linearly affects the unstressed isotropic moduli with a slope determined by their adiabatic pressure derivatives. The induced deviatoric stress produces anisotropic compressional and shear wave speeds; the latter result in shear wave splitting. For forward modelling purposes, we determine the weak form of the equation of motion under induced stress. In the context of the inverse problem, we determine induced stress sensitivity kernels, which may be used for adjoint tomography. The theory is illustrated by considering 2-D propagation of SH waves and related Fréchet derivatives based on a spectral-element method.

  4. Pre-cold stress increases acid stress resistance and induces amino ...

    African Journals Online (AJOL)

    pre-adapted to cold stress revealed induction of amino acid homeostasis and energy ... substrate, thereby reducing yeast and mould ..... spontaneous mutation of llmg_1816 (gdpp) induced by .... species to UV-B-induced damage in bacteria. J.

  5. Effect of stress on serum lipid levels in lady health visitors and housewives

    International Nuclear Information System (INIS)

    Wattoo, F.H.; Memon, M.S.; Memon, A.N.; Wattoo, M.H.S.; Tirmizi, S.A.; Iqbal, J.

    2007-01-01

    To study the effects of stress among lady health visitors and housewives in regard to their serum total cholesterol, HDL cholesterol, and LDL cholesterol and triglyceride levels. The study was performed at the Institute of Biochemistry, University of Sindh, Jamshoro, Pakistan during the years 2003 to 2005. Seventy lady health visitor and housewives aged between 25-40 years participated in this study and were selected from Hyderabad and its adjoining areas. Environmental, psychological and physiological stress levels were measured with likert scale. Total cholesterol, LDL cholesterol and HDL cholesterol and triglyceride levels were measured. Environmental, psychological and physiological stresses were significantly higher in housewives as compared to lady health visitors. A low level of HDL cholesterol was observed in housewives as compared to lady health visitors. The levels of total cholesterol, LDL cholesterol and triglyceride were found higher in housewives than lady health visitors. Housewives are under more stress than lady health visitors. The levels of total cholesterol, LDL cholesterol and triglyceride increases but HDL cholesterol decrease with stress. (author)

  6. Effects of Salvadora persica Extract on the Hematological and Biochemical Alterations against Immobilization-Induced Rats

    Science.gov (United States)

    Ramadan, Kholoud S.; Alshamrani, Salha A.

    2015-01-01

    A total of 24 rats were divided into 4 groups: control, stress, extract alone, and stress + extract (n = 6 each), for total 21 days of treatment. The immobilization stress was induced in rats by putting them in 20 cm × 7 cm plastic tubes for 2 h/day for 21 days. Rats were postorally treated with Salvadora persica at a dose of 900 mg/kg body weight via intragastric intubations. At the end of the test period, hematological and biochemical parameters were determined in blood and serum samples with determination of vital organs weights. The vital organ weights were not significantly affected in stressed rats as compared to control rats. Compared to the control group, the stress treated group showed significances in several hematological parameters, including decreases in WBC, RBC, and PLT counts. Furthermore, in comparison to the control group, the stress group showed significantly increased blood glucose, serum total cholesterol, LDL-cholesterol, and triacylglycerols levels and decreased HDL-cholesterol level. The hematological and biochemical parameters in the stress + extract treated group were approximately similar to control group. The SP extract restored the changes observed following stress treatment. PMID:26221565

  7. Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice.

    Science.gov (United States)

    Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Santos, Danúbia B; Ribeiro, Camille M; Rosa, Priscila B; Farina, Marcelo; Rodrigues, Ana Lúcia S

    2014-04-03

    Agmatine has been recently emerged as a novel candidate to assist the conventional pharmacotherapy of depression. The acute restraint stress (ARS) is an unavoidable stress situation that may cause depressive-like behavior in rodents. In this study, we investigated the potential antidepressant-like effect of agmatine (10mg/kg, administered acutely by oral route) in the forced swimming test (FST) in non-stressed mice, as well as its ability to abolish the depressive-like behavior and hippocampal antioxidant imbalance induced by ARS. Agmatine reduced the immobility time in the mouse FST (1-100mg/kg) in non-stressed mice. ARS caused an increase in the immobility time in the FST, indicative of a depressive-like behavior, as well as hippocampal lipid peroxidation, and an increase in the activity of hippocampal superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, reduced catalase (CAT) activity and increased SOD/CAT ratio, an index of pro-oxidative conditions. Agmatine was effective to abolish the depressive-like behavior induced by ARS and to prevent the ARS-induced lipid peroxidation and changes in SOD, GR and CAT activities and in SOD/CAT activity ratio. Hippocampal levels of reduced glutathione (GSH) were not altered by any experimental condition. In conclusion, the present study shows that agmatine was able to abrogate the ARS-induced depressive-like behavior and the associated redox hippocampal imbalance observed in stressed restraint mice, suggesting that its antidepressant-like effect may be dependent on its ability to maintain the pro-/anti-oxidative homeostasis in the hippocampus. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Docosahexaenoic acid inhibits monocrotaline-induced pulmonary hypertension via attenuating endoplasmic reticulum stress and inflammation.

    Science.gov (United States)

    Chen, Rui; Zhong, Wei; Shao, Chen; Liu, Peijing; Wang, Cuiping; Wang, Zhongqun; Jiang, Meiping; Lu, Yi; Yan, Jinchuan

    2018-02-01

    Endoplasmic reticulum (ER) stress and inflammation contribute to pulmonary hypertension (PH) pathogenesis. Previously, we confirmed that docosahexaenoic acid (DHA) could improve hypoxia-induced PH. However, little is known about the link between DHA and monocrotaline (MCT)-induced PH. Our aims were, therefore, to evaluate the effects and molecular mechanisms of DHA on MCT-induced PH in rats. Rat PH was induced by MCT. Rats were treated with DHA daily in the prevention group (following MCT injection) and the reversal group (after MCT injection for 2 wk) by gavage. After 4 wk, mean pulmonary arterial pressure (mPAP), right ventricular (RV) hypertrophy index, and morphological and immunohistochemical analyses were evaluated. Rat pulmonary artery smooth muscle cells (PASMCs) were used to investigate the effects of DHA on cell proliferation stimulated by platelet-derived growth factor (PDGF)-BB. DHA decreased mPAP and attenuated pulmonary vascular remodeling and RV hypertrophy, which were associated with suppressed ER stress. DHA blocked the mitogenic effect of PDGF-BB on PASMCs and arrested the cell cycle via inhibiting nuclear factor of activated T cells-1 (NFATc1) expression and activation and regulating cell cycle-related proteins. Moreover, DHA ameliorated inflammation in lung and suppressed macrophage and T lymphocyte accumulation in lung and adventitia of resistance pulmonary arteries. These findings suggest that DHA could protect against MCT-induced PH by reducing ER stress, suppressing cell proliferation and inflammation.

  9. Roselle supplementation prevents nicotine-induced vascular endothelial dysfunction and remodelling in rats.

    Science.gov (United States)

    Si, Lislivia Yiang-Nee; Kamisah, Yusof; Ramalingam, Anand; Lim, Yi Cheng; Budin, Siti Balkis; Zainalabidin, Satirah

    2017-07-01

    Vascular endothelial dysfunction (VED) plays an important role in the initiation of cardiovascular diseases. Roselle, enriched with antioxidants, demonstrates high potential in alleviating hypertension. This study was undertaken to investigate the effects of roselle supplementation of VED and remodelling in a rodent model with prolonged nicotine administration. Male Sprague-Dawley rats (n = 6 per group) were administered with 0.6 mg/kg nicotine for 28 days to induce VED. The rats were given either aqueous roselle (100 mg/kg) or normal saline orally 30 min prior to nicotine injection daily. One additional group of rats served as control. Thoracic aorta was isolated from rats to measure vascular reactivity, vascular remodelling and oxidative stress. Roselle significantly lowered aortic sensitivity to phenylephrine-induced vasoconstriction (Endo-(+) C max = 234.5 ± 3.9%, Endo-(-) C max = 247.6 ± 5.2%) compared with untreated nicotine group (Endo-(+) C max = 264.5 ± 6.9%, Endo-(-) C max = 276.5 ± 6.8%). Roselle also improved aortic response to endothelium-dependent vasodilator, acetylcholine (Endo-(+) R max = 73.2 ± 2.1%, Endo-(-) R max = 26.2 ± 0.8%) compared to nicotine group (Endo-(+) R max = 57.8 ± 1.7%, Endo-(-) R max = 20.9 ± 0.8%). In addition, roselle prevented an increase in intimal media thickness and elastic lamellae proliferation to preserve vascular architecture. Moreover, we also observed a significantly lowered degree of oxidative stress in parallel with increased antioxidant enzymes in aortic tissues of the roselle-treated group. This study demonstrated that roselle prevents VED and remodelling, and as such it has high nutraceutical value as supplement to prevent cardiovascular diseases.

  10. Glucagon-Like Peptide 1 Prevents Reactive Oxygen Species-Induced Endothelial Cell Senescence Through the Activation of Protein Kinase A

    NARCIS (Netherlands)

    Oeseburg, Hisko; de Boer, Rudolf A.; Buikema, Hendrik; van der Harst, Pim; van Gilst, Wiek H.; Sillje, Herman H. W.

    Objective-Endothelial cell senescence is an important contributor to vascular aging and is increased under diabetic conditions. Here we investigated whether the antidiabetic hormone glucagon-like peptide 1 (GLP-1) could prevent oxidative stress-induced cellular senescence in endothelial cells.

  11. Central mechanisms of stress-induced headache.

    Science.gov (United States)

    Cathcart, S; Petkov, J; Winefield, A H; Lushington, K; Rolan, P

    2010-03-01

    Stress is the most commonly reported trigger of an episode of chronic tension-type headache (CTTH); however, the causal significance has not been experimentally demonstrated to date. Stress may trigger CTTH through hyperalgesic effects on already sensitized pain pathways in CTTH sufferers. This hypothesis could be partially tested by examining pain sensitivity in an experimental model of stress-induced headache in CTTH sufferers. Such examinations have not been reported to date. We measured pericranial muscle tenderness and pain thresholds at the finger, head and shoulder in 23 CTTH sufferers (CTH-S) and 25 healthy control subjects (CNT) exposed to an hour-long stressful mental task, and in 23 CTTH sufferers exposed to an hour-long neutral condition (CTH-N). Headache developed in 91% of CTH-S, 4% of CNT, and 17% of CTH-N subjects. Headache sufferers had increased muscle tenderness and reduced pain thresholds compared with healthy controls. During the task, muscle tenderness increased and pain thresholds decreased in the CTH-S group compared with CTH-N and CNT groups. Pre-task muscle tenderness and reduction in pain threshold during task were predictive of the development and intensity of headache following task. The main findings are that stress induced a headache in CTTH sufferers, and this was associated with pre-task muscle tenderness and stress-induced reduction in pain thresholds. The results support the hypothesis that stress triggers CTTH through hyperalgesic effects on already increased pain sensitivity in CTTH sufferers, reducing the threshold to noxious input from pericranial structures.

  12. Prevention and reversal of social stress-escalated cocaine self-administration in mice by intra-VTA CRFR1 antagonism.

    Science.gov (United States)

    Han, Xiao; DeBold, Joseph F; Miczek, Klaus A

    2017-09-01

    A history of brief intermittent social defeat stress can escalate cocaine self-administration and induce long-term adaptations in the mesolimbic dopamine system. Extra-hypothalamic corticotrophin releasing factor (CRF) has been shown to be closely associated with stress-induced escalation of drug use. How repeated stress modulates CRF release in the ventral tegmental area (VTA) and the roles of CRF receptors during different phases of stress-induced cocaine self-administration remain to be defined. The current study examines the roles of CRF and CRF receptor 1 (CRFR1) in escalated intravenous cocaine self-administration after exposure to social defeat stress in mice. First, CRFR1 antagonist (CP 376,395, 15 mg/kg, i.p.) given 30 min prior to each social defeat episode prevented later escalated cocaine self-administration. When CP 376,395 (5 and 15 mg/kg, i.p.) was administered 10 days after the last episode of social stress, the escalation of cocaine intake was dose-dependently reversed. Moreover, socially defeated mice showed increased CRF release in the VTA compared to controls. To further explore the role of CRFR1, CP 376,395 (0.5 and 1 μg/0.2 μl) was infused directly into the VTA before the cocaine self-administration session. Intra-VTA antagonism of CRFR1 was sufficient to reverse social defeat stress-escalated cocaine self-administration. These findings suggest that CRF and CRFR1 exert multiple roles in the response to social stress that are relevant to escalated cocaine self-administration.

  13. What Is Cholesterol?

    Science.gov (United States)

    ... of Cholesterol There are two main types of cholesterol: LDL and HDL. The cholesterol blood test tells how much of each kind you have. Most cholesterol is LDL (low-density lipoprotein) cholesterol. This type is most ...

  14. THE CORRELATION BETWEEN LIPID PROFILE AND STRESS LEVELS IN PART CENTRAL IRAN: ISFAHAN HEALTHY HEART PROGRAM

    Directory of Open Access Journals (Sweden)

    Maryam Shahnam

    2010-12-01

    Full Text Available Abstract            Background: Previous studies suggest that mental status may influence serum lipid levels. This study was conducted on adult population living in rural and urban areas in Central Iran to assess the correlation between stress level and lipid profile disorders.Methods: Data was extracted from final evaluation of Isfahan Healthy Heart Program (IHHP in 2008. Multistage and random cluster methods were used for sampling. The study population consisted of 9752 adults aged ≥19 years living in three districts namely Isfahan, Arak and Najaf Abad. Demographic data, age and sex were recorded. Blood samples were taken to determine the lipid levels including total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, low levels of high-density lipoprotein cholesterol (HDL-C and triglycerides. Stress levels were assessed using the General Health Questionnaire. Logistic regression and chi-square tests were used for statistical analysis.Results: The odds ratios of high stress in individuals with high levels of TC, LDL-C and low levels of HDL-C compared to normal individuals after adjustment for age and sex were as follows respectively: 1.05 (1.02,1.15, 1.06 (1.02,1.18, 1.06 (1.01,1.17.Conclusion: Intervention activities towards reduction of stress levels at the community level may be useful as part of the strategy for cardiovascular disease prevention. Keywords: Cholesterol, Triglycerides, Stress, Questionnaire, Adult

  15. Oxidative stress and sodium methyldithiocarbamate-induced modulation of the macrophage response to lipopolysaccharide in vivo.

    Science.gov (United States)

    Pruett, Stephen B; Cheng, Bing; Fan, Ruping; Tan, Wei; Sebastian, Thomas

    2009-06-01

    Sodium methyldithiocarbamate (SMD) is the third most abundantly used conventional pesticide in the United States, and hundreds of thousands of persons are exposed to this compound or its major breakdown product, methylisothiocyanate, at levels greater than recommended by the Environmental Protection Agency. A previous study suggests three mechanisms of action involved to some degree in the inhibition of inflammation and decreased resistance to infection caused by exposure of mice to the compound. One of these mechanisms is oxidative stress. The purpose of the present study was to confirm that this mechanism is involved in the effects of SMD on cytokine production by peritoneal macrophages and to further characterize its role in altered cytokine production. Results indicated that SMD significantly decreased the intracellular concentration of reduced glutathione (GSH), suggesting oxidative stress. This was further indicated by the upregulation of genes involved in the "response to oxidative stress" as determined by microarray analysis. These effects were associated with the inhibition of lipopolysaccharide (LPS)-induced production of several proinflammatory cytokines. Experimental depletion of GSH with buthionine sulfoximine (BSO) partially prevented the decrease in LPS-induced interleukin (IL)-6 production caused by SMD and completely prevented the decrease in IL-12. In contrast, BSO plus SMD substantially enhanced the production of IL-10. These results along with results from a previous study are consistent with the hypothesis that SMD causes oxidative stress, which contributes to modulation of cytokine production. However, oxidative stress alone cannot explain the increased IL-10 production caused by SMD.

  16. Effect of hypocholesterolemia on cholesterol synthesis in small intestine of diabetic rats

    International Nuclear Information System (INIS)

    Feingold, K.R.; Moser, A.H.

    1987-01-01

    Studies by our and other laboratories have demonstrated that cholesterol synthesis is increased in the small intestine of insulinopenic diabetic animals. In normal animals, many factors have been shown to regulate cholesterol synthesis in the small intestine, including changes in plasma cholesterol levels. The purpose of this study was to determine the effect of lowering plasma cholesterol levels on small intestine cholesterol synthesis in streptozocin-induced diabetic rats. In diabetic rats, 4-aminopyrazolo[3,4-d]pyrimidine (4-APP)-induced hypocholesterolemia (plasma cholesterol levels less than 20 mg/dl) resulted in a 2.5-fold increase in small intestine cholesterol synthesis, which was most marked in the distal small intestine, decreasing proximally. In the distal small intestine the incorporation of 3 H 2 O into cholesterol was 0.28 +/- 0.04 mumol.h-1.g-1 in diabetic rats versus 1.60 +/- 0.38 in diabetic rats administered 4-APP (P less than .01). This stimulation of cholesterol synthesis occurred in the upper villus, middle villus, and crypt cells isolated from the middle intestine of the 4-APP-treated diabetic animals. In agreement with these observations, functional hypocholesterolemia due to Triton WR-1339 administration also stimulated cholesterol synthesis 2.5-fold in the small intestine of normal and diabetic animals. In the distal small intestine, cholesterol synthesis was 0.43 +/- 0.10 mumol.h-1.g-1 in the diabetic rats versus 1.08 +/- 0.21 in diabetic rats treated with Triton WR-1339 (P less than .05). In both the 4-APP and Triton WR-1339 experiments, the response of the diabetic rats was similar to that observed in normal rats

  17. Ubiquitin fold modifier 1 (UFM1 and its target UFBP1 protect pancreatic beta cells from ER stress-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Katleen Lemaire

    Full Text Available UFM1 is a member of the ubiquitin like protein family. While the enzymatic cascade of UFM1 conjugation has been elucidated in recent years, the biological function remains largely unknown. In this report we demonstrate that the recently identified C20orf116, which we name UFM1-binding protein 1 containing a PCI domain (UFBP1, and CDK5RAP3 interact with UFM1. Components of the UFM1 conjugation pathway (UFM1, UFBP1, UFL1 and CDK5RAP3 are highly expressed in pancreatic islets of Langerhans and some other secretory tissues. Co-localization of UFM1 with UFBP1 in the endoplasmic reticulum (ER depends on UFBP1. We demonstrate that ER stress, which is common in secretory cells, induces expression of Ufm1, Ufbp1 and Ufl1 in the beta-cell line INS-1E. siRNA-mediated Ufm1 or Ufbp1 knockdown enhances apoptosis upon ER stress. Silencing the E3 enzyme UFL1, results in similar outcomes, suggesting that UFM1-UFBP1 conjugation is required to prevent ER stress-induced apoptosis. Together, our data suggest that UFM1-UFBP1 participate in preventing ER stress-induced apoptosis in protein secretory cells.

  18. Reference intervals for serum total cholesterol, HDL cholesterol and ...

    African Journals Online (AJOL)

    Reference intervals of total cholesterol, HDL cholesterol and non-HDL cholesterol concentrations were determined on 309 blood donors from an urban and peri-urban population of Botswana. Using non-parametric methods to establish 2.5th and 97.5th percentiles of the distribution, the intervals were: total cholesterol 2.16 ...

  19. Cholesterol Efflux Capacity, High-Density Lipoprotein Particle Number, and Incident Cardiovascular Events: An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin).

    Science.gov (United States)

    Khera, Amit V; Demler, Olga V; Adelman, Steven J; Collins, Heidi L; Glynn, Robert J; Ridker, Paul M; Rader, Daniel J; Mora, Samia

    2017-06-20

    Recent failures of drugs that raised high-density lipoprotein (HDL) cholesterol levels to reduce cardiovascular events in clinical trials have led to increased interest in alternative indices of HDL quality, such as cholesterol efflux capacity, and HDL quantity, such as HDL particle number. However, no studies have directly compared these metrics in a contemporary population that includes potent statin therapy and low low-density lipoprotein cholesterol. HDL cholesterol levels, apolipoprotein A-I, cholesterol efflux capacity, and HDL particle number were assessed at baseline and 12 months in a nested case-control study of the JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), a randomized primary prevention trial that compared rosuvastatin treatment to placebo in individuals with normal low-density lipoprotein cholesterol but increased C-reactive protein levels. In total, 314 cases of incident cardiovascular disease (CVD) (myocardial infarction, unstable angina, arterial revascularization, stroke, or cardiovascular death) were compared to age- and gender-matched controls. Conditional logistic regression models adjusting for risk factors evaluated associations between HDL-related biomarkers and incident CVD. Cholesterol efflux capacity was moderately correlated with HDL cholesterol, apolipoprotein A-I, and HDL particle number (Spearman r = 0.39, 0.48, and 0.39 respectively; P capacity (OR/SD, 0.89; 95% CI, 0.72-1.10; P =0.28), HDL cholesterol (OR/SD, 0.82; 95% CI, 0.66-1.02; P =0.08), or apolipoprotein A-I (OR/SD, 0.83; 95% CI, 0.67-1.03; P =0.08). Twelve months of rosuvastatin (20 mg/day) did not change cholesterol efflux capacity (average percentage change -1.5%, 95% CI, -13.3 to +10.2; P =0.80), but increased HDL cholesterol (+7.7%), apolipoprotein A-I (+4.3%), and HDL particle number (+5.2%). On-statin cholesterol efflux capacity was inversely associated with incident CVD (OR/SD, 0.62; 95% CI, 0

  20. The cholesterol system of the swine

    International Nuclear Information System (INIS)

    Aigueperse, Jocelyne

    1979-01-01

    The purpose of this work was to characterize the dynamic system of adult female Large White swine. The content of this system and its relationships with both the external environment and between the different parts of the system were explained. The analysis of these results in terms of compared physiology showed that the structure of the cholesterol system was the same in man and in the swine. Consequently, the swine constitutes a good biological tool to study human cholesterol indirectly and to foresee the changes that might be induced in various physio-pathological cases. (author) [fr

  1. Aldolase B knockdown prevents high glucose-induced methylglyoxal overproduction and cellular dysfunction in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Jianghai Liu

    Full Text Available We used cultured endothelial cells as a model to examine whether up-regulation of aldolase B and enhanced methylglyoxal (MG formation play an important role in high glucose-induced overproduction of advanced glycosylation endproducts (AGEs, oxidative stress and cellular dysfunction. High glucose (25 mM incubation up-regulated mRNA levels of aldose reductase (an enzyme converting glucose to fructose and aldolase B (a key enzyme that catalyzes MG formation from fructose and enhanced MG formation in human umbilical vein endothelial cells (HUVECs and HUVEC-derived EA. hy926 cells. High glucose-increased MG production in EA. hy926 cells was completely prevented by siRNA knockdown of aldolase B, but unaffected by siRNA knockdown of aldolase A, an enzyme responsible for MG formation during glycolysis. In addition, inhibition of cytochrome P450 2E1 or semicarbazide-sensitive amine oxidase which produces MG during the metabolism of lipid and proteins, respectively, did not alter MG production. Both high glucose (25 mM and MG (30, 100 µM increased the formation of N(ε-carboxyethyl-lysine (CEL, a MG-induced AGE, oxidative stress (determined by the generation of oxidized DCF, H(2O(2, protein carbonyls and 8-oxo-dG, O-GlcNAc modification (product of the hexosamine pathway, membrane protein kinase C activity and nuclear translocation of NF-κB in EA. hy926 cells. However, the above metabolic and signaling alterations induced by high glucose were completely prevented by knockdown of aldolase B and partially by application of aminoguanidine (a MG scavenger or alagebrium (an AGEs breaker. In conclusion, efficient inhibition of aldolase B can prevent high glucose-induced overproduction of MG and related cellular dysfunction in endothelial cells.

  2. The Aurora-B-dependent NoCut checkpoint prevents damage of anaphase bridges after DNA replication stress.

    Science.gov (United States)

    Amaral, Nuno; Vendrell, Alexandre; Funaya, Charlotta; Idrissi, Fatima-Zahra; Maier, Michael; Kumar, Arun; Neurohr, Gabriel; Colomina, Neus; Torres-Rosell, Jordi; Geli, María-Isabel; Mendoza, Manuel

    2016-05-01

    Anaphase chromatin bridges can lead to chromosome breakage if not properly resolved before completion of cytokinesis. The NoCut checkpoint, which depends on Aurora B at the spindle midzone, delays abscission in response to chromosome segregation defects in yeast and animal cells. How chromatin bridges are detected, and whether abscission inhibition prevents their damage, remain key unresolved questions. We find that bridges induced by DNA replication stress and by condensation or decatenation defects, but not dicentric chromosomes, delay abscission in a NoCut-dependent manner. Decatenation and condensation defects lead to spindle stabilization during cytokinesis, allowing bridge detection by Aurora B. NoCut does not prevent DNA damage following condensin or topoisomerase II inactivation; however, it protects anaphase bridges and promotes cellular viability after replication stress. Therefore, the molecular origin of chromatin bridges is critical for activation of NoCut, which plays a key role in the maintenance of genome stability after replicative stress.

  3. Adzuki bean ameliorates hepatic lipogenesis and proinflammatory mediator expression in mice fed a high-cholesterol and high-fat diet to induce nonalcoholic fatty liver disease.

    Science.gov (United States)

    Kim, Sera; Hong, Jihye; Jeon, Raok; Kim, Hyun-Sook

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a simple steatosis, in which fat accumulates more than 5% in the liver, and regarded as most common liver diseases worldwide. Because NAFLD can be developed to severe liver disease and correlated with metabolic disease, its importance is currently emphasized. Occurrence of NAFLD is strongly related to dietary patterns and lifestyles; therefore, the suggestion of physiologically beneficial food is essential. Based on these, adzuki beans containing anthocyanin, catechin, and adzukisaponin are suggested as a health-beneficial food. Moreover, the effects of adzuki beans on metabolic improvement are not well established through the in vivo studies. Therefore, this study hypothesized that adzuki beans can alleviate lipid accumulation and oxidative stress-mediated inflammation in high-cholesterol and high-fat diet-induced NALFD mice. To demonstrate its effects, 6-week-old C57BL/6 male mice were allocated into 4 groups and fed a normal diet (ND), a high-cholesterol and high-fat diet (HCD), and HCD with 10% and 20% adzuki bean for 10 weeks. The result shows that fasting blood glucose, serum and hepatic triglyceride and cholesterol levels, and antioxidative enzyme activity ameliorated in the adzuki bean groups (P hepatic lipogenesis, such as adiponectin, AMP-activated protein kinase α, sterol regulatory element-binding protein 1c, fatty acid synthase, carnitine palmitoyltransferase 1, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and apolipoprotein B, as well as proinflammatory mediators, such as tumor necrosis factor α, nuclear factor κB, and caspase-3, improved in both experimental groups (P hepatic messenger RNA expression of lipogenic and inflammatory mediators in NAFLD. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Ghrelin mediates stress-induced food-reward behavior in mice.

    Science.gov (United States)

    Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Savitt, Joseph M; Lutter, Michael; Zigman, Jeffrey M

    2011-07-01

    The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense "comfort foods." Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin's orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating.

  5. Lateralized kappa opioid receptor signaling from the amygdala central nucleus promotes stress-induced functional pain.

    Science.gov (United States)

    Nation, Kelsey M; De Felice, Milena; Hernandez, Pablo I; Dodick, David W; Neugebauer, Volker; Navratilova, Edita; Porreca, Frank

    2018-05-01

    The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus). Morphine priming without stress did not alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in both hind paws that was abolished by systemic administration of the KOR antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the right, but not left, central nucleus of the amygdala (CeA) prevented the loss of DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress increased dynorphin content in both the left and right CeA of primed rats, reaching significance only in the right CeA; no change was observed in the rostral ventromedial medulla or hypothalamus. Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders.

  6. Impact of mechanical stress induced in silica vacuum windows on laser-induced damage.

    Science.gov (United States)

    Gingreau, Clémence; Lanternier, Thomas; Lamaignère, Laurent; Donval, Thierry; Courchinoux, Roger; Leymarie, Christophe; Néauport, Jérôme

    2018-04-15

    At the interface between vacuum and air, optical windows must keep their optical properties, despite being subjected to mechanical stress. In this Letter, we investigate the impact of such stress on the laser-induced damage of fused silica windows at the wavelength of 351 nm in the nanosecond regime. Different stress values, from 1 to 30 MPa, both tensile and compressive, were applied. No effect of the stress on the laser-induced damage was evidenced.

  7. Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception.

    Science.gov (United States)

    Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang

    2015-12-02

    Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. In this study, we showed that pre- or post-surgical exposure to immobilization 6 h daily for three consecutive days did not change basal responses to mechanical, thermal, or cold stimuli or peak levels of incision-induced hypersensitivity to these stimuli; however, immobilization did prolong the duration of incision-induced hypersensitivity in both male and female rats. These phenomena were also observed in post-surgical exposure to forced swimming 25 min daily for 3 consecutive days. Short-term stress induced by immobilization was demonstrated by an elevation in the level of serum corticosterone, an increase in swim immobility, and a decrease in sucrose consumption. Blocking this short-term stress via intrathecal administration of a selective glucocorticoid receptor antagonist, RU38486, or bilateral adrenalectomy significantly attenuated the prolongation of incision-induced hypersensitivity to mechanical, thermal, and cold stimuli. Our results indicate that short-term stress during the pre- or post-operative period delays postoperative pain recovery although it does not affect basal pain perception. Prevention of short-term stress may facilitate patients' recovery from postoperative pain.

  8. Increased expression of RXRα in dementia: an early harbinger for the cholesterol dyshomeostasis?

    Directory of Open Access Journals (Sweden)

    Katsel Pavel

    2010-09-01

    Full Text Available Abstract Background Cholesterol content of cerebral membranes is tightly regulated by elaborate mechanisms that balance the level of cholesterol synthesis, uptake and efflux. Among the conventional regulatory elements, a recent research focus has been nuclear receptors, a superfamily of ligand-activated transcription factors providing an indispensable regulatory framework in controlling cholesterol metabolism pathway genes. The mechanism of transcriptional regulation by nuclear receptors such as LXRs involves formation of heterodimers with RXRs. LXR/RXR functions as a sensor of cellular cholesterol concentration and mediates cholesterol efflux by inducing the transcription of key cholesterol shuffling vehicles namely, ATP-binding cassette transporter A1 (ABCA1 and ApoE. Results In the absence of quantitative data from humans, the relevance of expression of nuclear receptors and their involvement in cerebral cholesterol homeostasis has remained elusive. In this work, new evidence is provided from direct analysis of human postmortem brain gene and protein expression suggesting that RXRα, a key regulator of cholesterol metabolism is differentially expressed in individuals with dementia. Importantly, RXRα expression showed strong association with ABCA1 and ApoE gene expression, particularly in AD vulnerable regions. Conclusions These findings suggest that LXR/RXR-induced upregulation of ABCA1 and ApoE levels may be the molecular determinants of cholesterol dyshomeostasis and of the accompanying dementia observed in AD.

  9. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice

    DEFF Research Database (Denmark)

    Patrick, David M; Montgomery, Rusty L; Qi, Xiaoxia

    2010-01-01

    MicroRNAs inhibit mRNA translation or promote mRNA degradation by binding complementary sequences in 3' untranslated regions of target mRNAs. MicroRNA-21 (miR-21) is upregulated in response to cardiac stress, and its inhibition by a cholesterol-modified antagomir has been reported to prevent card...

  10. Essential fatty acid-rich diets protect against striatal oxidative damage induced by quinolinic acid in rats.

    Science.gov (United States)

    Morales-Martínez, Adriana; Sánchez-Mendoza, Alicia; Martínez-Lazcano, Juan Carlos; Pineda-Farías, Jorge Baruch; Montes, Sergio; El-Hafidi, Mohammed; Martínez-Gopar, Pablo Eliasib; Tristán-López, Luis; Pérez-Neri, Iván; Zamorano-Carrillo, Absalom; Castro, Nelly; Ríos, Camilo; Pérez-Severiano, Francisca

    2017-09-01

    Essential fatty acids have an important effect on oxidative stress-related diseases. The Huntington's disease (HD) is a hereditary neurologic disorder in which oxidative stress caused by free radicals is an important damage mechanism. The HD experimental model induced by quinolinic acid (QUIN) has been widely used to evaluate therapeutic effects of antioxidant compounds. The aim of this study was to test whether the fatty acid content in olive- or fish-oil-rich diet prevents against QUIN-related oxidative damage in rats. Rats were fed during 20 days with an olive- or a fish-oil-rich diet (15% w/w). Posterior to diet period, rats were striatally microinjected with QUIN (240 nmol/µl) or saline solution. Then, we evaluated the neurological damage, oxidative status, and gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) expression. Results showed that fatty acid-rich diet, mainly by fish oil, reduced circling behavior, prevented the fall in GABA levels, increased PPARγ expression, and prevented oxidative damage in striatal tissue. In addition none of the enriched diets exerted changes neither on triglycerides or cholesterol blood levels, nor or hepatic function. This study suggests that olive- and fish-oil-rich diets exert neuroprotective effects.

  11. The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading

    Directory of Open Access Journals (Sweden)

    Anna Baulies

    2018-04-01

    Full Text Available Cancer cells exhibit mitochondrial cholesterol (mt-cholesterol accumulation, which contributes to cell death resistance by antagonizing mitochondrial outer membrane (MOM permeabilization. Hepatocellular mt-cholesterol loading, however, promotes steatohepatitis, an advanced stage of chronic liver disease that precedes hepatocellular carcinoma (HCC, by depleting mitochondrial GSH (mGSH due to a cholesterol-mediated impairment in mGSH transport. Whether and how HCC cells overcome the restriction of mGSH transport imposed by mt-cholesterol loading to support mGSH uptake remains unknown. Although the transport of mGSH is not fully understood, SLC25A10 (dicarboxylate carrier, DIC and SLC25A11 (2-oxoglutarate carrier, OGC have been involved in mGSH transport, and therefore we examined their expression and role in HCC. Unexpectedly, HCC cells and liver explants from patients with HCC exhibit divergent expression of these mitochondrial carriers, with selective OGC upregulation, which contributes to mGSH maintenance. OGC but not DIC downregulation by siRNA depleted mGSH levels and sensitized HCC cells to hypoxia-induced ROS generation and cell death as well as impaired cell growth in three-dimensional multicellular HCC spheroids, effects that were reversible upon mGSH replenishment by GSH ethyl ester, a membrane permeable GSH precursor. We also show that OGC regulates mitochondrial respiration and glycolysis. Moreover, OGC silencing promoted hypoxia-induced cardiolipin peroxidation, which reversed the inhibition of cholesterol on the permeabilization of MOM-like liposomes induced by Bax or Bak. Genetic OGC knockdown reduced the ability of tumor-initiating stem-like cells to induce liver cancer. These findings underscore the selective overexpression of OGC as an adaptive mechanism of HCC to provide adequate mGSH levels in the face of mt-cholesterol loading and suggest that OGC may be a novel therapeutic target for HCC treatment. Keywords: Cholesterol

  12. Diet-induced metabolic hamster model of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Bhathena J

    2011-06-01

    Full Text Available Jasmine Bhathena, Arun Kulamarva, Christopher Martoni, Aleksandra Malgorzata Urbanska, Meenakshi Malhotra, Arghya Paul, Satya PrakashBiomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Québec, CanadaBackground: Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology.Methods: Experiments were planned to develop a diet-induced Bio F1B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O.Results: In this study, we established a diet-induced Bio F1B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed

  13. Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

    Directory of Open Access Journals (Sweden)

    Beverley Greenwood-Van Meerveld

    2017-11-01

    Full Text Available Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS. Early life stress (ELS is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for

  14. Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

    Science.gov (United States)

    Greenwood-Van Meerveld, Beverley; Johnson, Anthony C.

    2017-01-01

    Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress-induced

  15. Skeletal muscle insulin resistance associated with cholesterol-induced activation of macrophages is prevented by high density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Andrew L Carey

    Full Text Available BACKGROUND: Emerging evidence suggests that high density lipoprotein (HDL may modulate glucose metabolism through multiple mechanisms including pancreatic insulin secretion as well as insulin-independent glucose uptake into muscle. We hypothesized that HDL may also increase skeletal muscle insulin sensitivity via cholesterol removal and anti-inflammatory actions in macrophages associated with excess adiposity and ectopic lipid deposition. METHODS: Human primary and THP-1 macrophages were treated with vehicle (PBS or acetylated low density lipoprotein (acLDL with or without HDL for 18 hours. Treatments were then removed, and macrophages were incubated with fresh media for 4 hours. This conditioned media was then applied to primary human skeletal myotubes derived from vastus lateralis biopsies taken from patients with type 2 diabetes to examine insulin-stimulated glucose uptake. RESULTS: Conditioned media from acLDL-treated primary and THP-1 macrophages reduced insulin-stimulated glucose uptake in primary human skeletal myotubes compared with vehicle (primary macrophages, 168±21% of basal uptake to 104±19%; THP-1 macrophages, 142±8% of basal uptake to 108±6%; P<0.05. This was restored by co-treatment of macrophages with HDL. While acLDL increased total intracellular cholesterol content, phosphorylation of c-jun N-terminal kinase and secretion of pro- and anti-inflammatory cytokines from macrophages, none were altered by co-incubation with HDL. Insulin-stimulated Akt phosphorylation in human skeletal myotubes exposed to conditioned media was unaltered by either treatment condition. CONCLUSION: Inhibition of insulin-stimulated glucose uptake in primary human skeletal myotubes by conditioned media from macrophages pre-incubated with acLDL was restored by co-treatment with HDL. However, these actions were not linked to modulation of common pro- or anti-inflammatory mediators or insulin signaling via Akt.

  16. Strategies for increasing house staff management of cholesterol with inpatients.

    Science.gov (United States)

    Boekeloo, B O; Becker, D M; Levine, D M; Belitsos, P C; Pearson, T A

    1990-01-01

    This study tested the effectiveness of two conceptually different chart audit-based approaches to modifying physicians' clinical practices to conform with quality-assurance standards. The objective was to increase intern utilization of cholesterol management opportunities in the inpatient setting. Using a clinical trial study design, 29 internal medicine interns were randomly assigned to four intervention groups identified by the intervention they received: control, reminder checklists (checklists), patient-specific feedback (feedback), or both interventions (combined). Over a nine-month period, intern management of high blood cholesterol levels in internal medicine inpatients (n = 459) was monitored by postdischarge chart audit. During both a baseline and subsequent intervention period, interns documented significantly more cholesterol management for inpatients with coronary artery disease (CAD) than without CAD. During baseline, 27.3%, 24.3%, 21.7%, 12.4%, 5.4%, and 2.7% of all inpatient charts had intern documentation concerning a low-fat hospital diet, cholesterol history, screening blood cholesterol level assessment, follow-up lipid profile, nutritionist consult, and preventive cardiology consult, respectively. The feedback intervention significantly increased overall intern-documented cholesterol management among inpatients with CAD. The checklists significantly decreased overall intern-documented cholesterol management. Feedback appears to be an effective approach to increasing intern cholesterol management in inpatients.

  17. Silymarin prevents acetaminophen-induced hepatotoxicity in mice.

    Directory of Open Access Journals (Sweden)

    Zuzana Papackova

    Full Text Available Acetaminophen or paracetamol (APAP overdose is a common cause of liver injury. Silymarin (SLM is a hepatoprotective agent widely used for treating liver injury of different origin. In order to evaluate the possible beneficial effects of SLM, Balb/c mice were pretreated with SLM (100 mg/kg b.wt. per os once daily for three days. Two hours after the last SLM dose, the mice were administered APAP (300 mg/kg b.wt. i.p. and killed 6 (T6, 12 (T12 and 24 (T24 hours later. SLM-treated mice exhibited a significant reduction in APAP-induced liver injury, assessed according to AST and ALT release and histological examination. SLM treatment significantly reduced superoxide production, as indicated by lower GSSG content, lower HO-1 induction, alleviated nitrosative stress, decreased p-JNK activation and direct measurement of mitochondrial superoxide production in vitro. SLM did not affect the APAP-induced decrease in CYP2E1 activity and expression during the first 12 hrs. Neutrophil infiltration and enhanced expression of inflammatory markers were first detected at T12 in both groups. Inflammation progressed in the APAP group at T24 but became attenuated in SLM-treated animals. Histological examination suggests that necrosis the dominant cell death pathway in APAP intoxication, which is partially preventable by SLM pretreatment. We demonstrate that SLM significantly protects against APAP-induced liver damage through the scavenger activity of SLM and the reduction of superoxide and peroxynitrite content. Neutrophil-induced damage is probably secondary to necrosis development.

  18. β-Adrenergic receptors desensitization is not involved in exercise-induced cardiac fatigue: NADPH oxidase-induced oxidative stress as a new trigger.

    Science.gov (United States)

    Vitiello, Damien; Boissière, Julien; Doucende, Grégory; Gayrard, Sandrine; Polge, Anne; Faure, Patrice; Goux, Aurélie; Tanguy, Stéphane; Obert, Philippe; Reboul, Cyril; Nottin, Stéphane

    2011-11-01

    Prolonged strenuous exercise (PSE) induces transient left ventricular (LV) dysfunction. Previous studies suggest that β-adrenergic pathway desensitization could be involved in this phenomenon, but it remains to be confirmed. Moreover, other underlying mechanisms involving oxidative stress have been recently proposed. The present study aimed to evaluate the involvement of both the β-adrenergic pathway and NADPH oxidase (Nox) enzyme-induced oxidative stress in myocardial dysfunction in rats following PSE. Rats were divided into 4 groups: controls (Ctrl), 4-h exercised on treadmill (PSE), and 2 groups in which Nox enzyme was inhibited with apocynin treatment (Ctrl APO and PSE APO, respectively). We evaluated cardiac function in vivo and ex vivo during basal conditions and isoproterenol stress. GSH/GSSG ratio, cardiac troponin I (cTnI) release, and lipid peroxidation (MDA) were evaluated. PSE induced a decrease in LV developed pressure, intrinsic myocardial contractility, and relaxation associated with an increase in plasma cTnI release. Our in vivo and ex vivo results demonstrated no differences in myocardial response to isoproterenol and of effective dose 50 between control and PSE rats. Interestingly, the LV dysfunction was reversed by apocynin treatment. Moreover, apocynin prevented cellular oxidation [GSH/GSSG ratio: PSE APO rats vs. PSE rats in arbitrary units (au): 1.98 ± 0.07 vs. 1.35 ± 0.10; P stress from the Nox enzyme.

  19. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial

    DEFF Research Database (Denmark)

    Sever, Peter S; Dahlöf, Björn; Poulter, Neil R

    2003-01-01

    The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome. No study, however, has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease (CHD) in hypertensive patients who are not conventionally deemed ...

  20. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial

    DEFF Research Database (Denmark)

    Sever, Peter S; Dahlöf, Björn; Poulter, Neil R

    2004-01-01

    The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome. No study, however, has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease (CHD) in hypertensive patients who are not conventionally deemed ...

  1. Structure-dependent behavior of stress-induced voiding in Cu interconnects

    International Nuclear Information System (INIS)

    Wu Zhenyu; Yang Yintang; Chai Changchun; Li Yuejin; Wang Jiayou; Li Bin; Liu Jing

    2010-01-01

    Stress modeling and cross-section failure analysis by focused-ion-beam have been used to investigate stress-induced voiding phenomena in Cu interconnects. The voiding mechanism and the effect of the interconnect structure on the stress migration have been studied. The results show that the most concentrated tensile stress appears and voids form at corners of vias on top surfaces of Cu M1 lines. A simple model of stress induced voiding in which vacancies arise due to the increase of the chemical potential under tensile stress and diffuse under the force of stress gradient along the main diffusing path indicates that stress gradient rather than stress itself determines the voiding rate. Cu interconnects with larger vias show less resistance to stress-induced voiding due to larger stress gradient at corners of vias.

  2. Effect of stress on serum cholestrol levels in nurses and housewives of Hyderabad - Pakistan

    International Nuclear Information System (INIS)

    Watto, F.H.; Memon, M.S.; Memon, A.N.; Ghanghro, A.B.; Yaquib, M.; Watto, M.H.S.; Tirmizi, S.A.

    2010-01-01

    A cohort type study was designed to evaluate environmental, psychological and physiological stresses in nurses and housewives and to correlate with their serum total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride levels. Total 160 females from middle socioeconomic groups (nurses, n=80 and housewives, n=80) aged between 25-45 years participated in this study and subjects were selected from Hyderabad and its adjoining areas. Environmental, psychological and physiological stress levels were measured with likert scale. Total cholesterol, LDL cholesterol and HDL cholesterol were measured by CHOD-PAP method and triglyceride levels were measured by GPO method. Housewives were found to have high levels of total cholesterol, LDL cholesterol and triglycerides. The HDL cholesterol were lower. Environmental, psychological and physiological stresses were significantly higher in housewives as compared to the nurses. Highest level of environmental stress was observed in nonworking group i.e. housewives. A significant relation between serum cholesterol levels and three types of stresses was observed. (author)

  3. Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin-Bae [The Division of Cardiology, Kyung Hee University College of Medicine, 1 Hoegi-dong, Dongdaemun-Gu, Seoul (Korea, Republic of); Kim, Changsoo [The Department of Preventive Medicine, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Choi, Eunmi [Cardiovascular Research Institute and Severance Biomedical Science Institute, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Park, Sanghoon; Park, Hyelim; Pak, Hui-Nam; Lee, Moon-Hyoung [The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Shin, Dong Chun [The Department of Preventive Medicine, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Hwang, Ki-Chul [Cardiovascular Research Institute and Severance Biomedical Science Institute, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Joung, Boyoung, E-mail: cby6908@yuhs.ac [The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of)

    2012-02-15

    Ambient particulate matter (PM) can increase the incidence of arrhythmia. However, the arrhythmogenic mechanism of PM is poorly understood. This study investigated the arrhythmogenic mechanism of PM. In Sprague–Dawley rats, QT interval was increased from 115.0 ± 14.0 to 142.1 ± 18.4 ms (p = 0.02) after endotracheal exposure of DEP (200 μg/ml for 30 min, n = 5). Ventricular premature contractions were more frequently observed after DEP exposure (100%) than baseline (20%, p = 0.04). These effects were prevented by pretreatment of N-acetylcysteine (NAC, 5 mmol/L, n = 3). In 12 Langendorff-perfused rat hearts, DEP infusion of 12.5 μg/ml for 20 min prolonged action potential duration (APD) at only left ventricular base increasing apicobasal repolarization gradients. Spontaneous early afterdepolarization (EAD) and ventricular tachycardia (VT) were observed in 8 (67%) and 6 (50%) hearts, respectively, versus no spontaneous triggered activity or VT in any hearts before DEP infusion. DEP-induced APD prolongation, EAD and VT were successfully prevented with NAC (5 mmol/L, n = 5), nifedipine (10 μmol/L, n = 5), and active Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1 μmol/L, n = 5), but not by thapsigargin (200 nmol/L) plus ryanodine (10 μmol/L, n = 5) and inactive CaMKII blockade, KN 92 (1 μmol/L, n = 5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5 μg/ml) induced apoptosis, and this effect was prevented by NAC and KN 93. Thus, this study shows that in vivo and vitro exposure of PM induced APD prolongation, EAD and ventricular arrhythmia. These effects might be caused by oxidative stress and CaMKII activation. -- Highlights: ► The ambient PM consistently prolonged repolarization. ► The ambient PM induced triggered activity and ventricular arrhythmia. ► These effects were prevented by antioxidants, I{sub CaL} blockade and CaMKII blockade. ► The ambient PM can induce

  4. Stress-induced variation in evolution: from behavioural plasticity to genetic assimilation.

    Science.gov (United States)

    Badyaev, Alexander V

    2005-05-07

    Extreme environments are closely associated with phenotypic evolution, yet the mechanisms behind this relationship are poorly understood. Several themes and approaches in recent studies significantly further our understanding of the importance that stress-induced variation plays in evolution. First, stressful environments modify (and often reduce) the integration of neuroendocrinological, morphological and behavioural regulatory systems. Second, such reduced integration and subsequent accommodation of stress-induced variation by developmental systems enables organismal 'memory' of a stressful event as well as phenotypic and genetic assimilation of the response to a stressor. Third, in complex functional systems, a stress-induced increase in phenotypic and genetic variance is often directional, channelled by existing ontogenetic pathways. This accounts for similarity among individuals in stress-induced changes and thus significantly facilitates the rate of adaptive evolution. Fourth, accumulation of phenotypically neutral genetic variation might be a common property of locally adapted and complex organismal systems, and extreme environments facilitate the phenotypic expression of this variance. Finally, stress-induced effects and stress-resistance strategies often persist for several generations through maternal, ecological and cultural inheritance. These transgenerational effects, along with both the complexity of developmental systems and stressor recurrence, might facilitate genetic assimilation of stress-induced effects. Accumulation of phenotypically neutral genetic variance by developmental systems and phenotypic accommodation of stress-induced effects, together with the inheritance of stress-induced modifications, ensure the evolutionary persistence of stress-response strategies and provide a link between individual adaptability and evolutionary adaptation.

  5. Irradiation-induced stress relaxation of Eurofer97 steel

    International Nuclear Information System (INIS)

    Luzginova, N.V.; Jong, M.; Rensman, J.W.; Hegeman, J.B.J.; Laan, J.G. van der

    2011-01-01

    The irradiation-induced stress relaxation behavior of Eurofer97 at 300 deg. C up to 3.4 dpa and under pre-stress loads typical for the ITER applications is investigated. The bolt specimens are pre-loaded from 30% to 90% of the yield strength. To verify the results obtained with the pre-stressed bolts, bent strips were investigated as well. The strips are bent into a pre-defined radius in order to achieve similar pre-stress levels. The irradiation-induced stress relaxation is found to be independent of the pre-stress level. 10-12% of the stress relaxation in Eurofer97 may be reached after a dose of 0.1 dpa, and after an irradiation dose of 2.7 dpa 42-47% of the original pre-stress is retained.

  6. Phenylbutyric acid rescues endoplasmic reticulum stress-induced suppression of APP proteolysis and prevents apoptosis in neuronal cells.

    Directory of Open Access Journals (Sweden)

    Jesse C Wiley

    Full Text Available BACKGROUND: The familial and sporadic forms of Alzheimer's disease (AD have an identical pathology with a severe disparity in the time of onset [1]. The pathological similarity suggests that epigenetic processes may phenocopy the Familial Alzheimer's disease (FAD mutations within sporadic AD. Numerous groups have demonstrated that FAD mutations in presenilin result in 'loss of function' of gamma-secretase mediated APP cleavage [2], [3], [4], [5]. Accordingly, ER stress is prominent within the pathologically impacted brain regions in AD patients [6] and is reported to inhibit APP trafficking through the secretory pathway [7], [8]. As the maturation of APP and the cleaving secretases requires trafficking through the secretory pathway [9], [10], [11], we hypothesized that ER stress may block trafficking requisite for normal levels of APP cleavage and that the small molecular chaperone 4-phenylbutyrate (PBA may rescue the proteolytic deficit. METHODOLOGY/PRINCIPAL FINDINGS: The APP-Gal4VP16/Gal4-reporter screen was stably incorporated into neuroblastoma cells in order to assay gamma-secretase mediated APP proteolysis under normal and pharmacologically induced ER stress conditions. Three unrelated pharmacological agents (tunicamycin, thapsigargin and brefeldin A all repressed APP proteolysis in parallel with activation of unfolded protein response (UPR signaling-a biochemical marker of ER stress. Co-treatment of the gamma-secretase reporter cells with PBA blocked the repressive effects of tunicamycin and thapsigargin upon APP proteolysis, UPR activation, and apoptosis. In unstressed cells, PBA stimulated gamma-secretase mediated cleavage of APP by 8-10 fold, in the absence of any significant effects upon amyloid production, by promoting APP trafficking through the secretory pathway and the stimulation of the non-pathogenic alpha/gamma-cleavage. CONCLUSIONS/SIGNIFICANCE: ER stress represses gamma-secretase mediated APP proteolysis, which replicates

  7. Implications of lower risk thresholds for statin treatment in primary prevention: analysis of CPRD and simulation modelling of annual cholesterol monitoring.

    Science.gov (United States)

    McFadden, Emily; Stevens, Richard; Glasziou, Paul; Perera, Rafael

    2015-01-01

    To estimate numbers affected by a recent change in UK guidelines for statin use in primary prevention of cardiovascular disease. We modelled cholesterol ratio over time using a sample of 45,151 men (≥40years) and 36,168 women (≥55years) in 2006, without statin treatment or previous cardiovascular disease, from the Clinical Practice Research Datalink. Using simulation methods, we estimated numbers indicated for new statin treatment, if cholesterol was measured annually and used in the QRISK2 CVD risk calculator, using the previous 20% and newly recommended 10% thresholds. We estimate that 58% of men and 55% of women would be indicated for treatment by five years and 71% of men and 73% of women by ten years using the 20% threshold. Using the proposed threshold of 10%, 84% of men and 90% of women would be indicated for treatment by 5years and 92% of men and 98% of women by ten years. The proposed change of risk threshold from 20% to 10% would result in the substantial majority of those recommended for cholesterol testing being indicated for statin treatment. Implications depend on the value of statins in those at low to medium risk, and whether there are harms. Copyright © 2014. Published by Elsevier Inc.

  8. Environmental enrichment and gut inflammation modify stress-induced c-Fos expression in the mouse corticolimbic system.

    Directory of Open Access Journals (Sweden)

    Florian Reichmann

    Full Text Available Environmental enrichment (EE has a beneficial effect on rodent behaviour, neuronal plasticity and brain function. Although it may also improve stress coping, it is not known whether EE influences the brain response to an external (psychological stressor such as water avoidance stress (WAS or an internal (systemic stressor such as gastrointestinal inflammation. This study hence explored whether EE modifies WAS-induced activation of the mouse corticolimbic system and whether this stress response is altered by gastritis or colitis. Male C67BL/6N mice were housed under standard or enriched environment for 9 weeks, after which they were subjected to a 1-week treatment with oral iodoacetamide to induce gastritis or oral dextran sulfate sodium to induce colitis. Following exposure to WAS the expression of c-Fos, a marker of neuronal activation, was measured by immunocytochemistry. EE aggravated experimentally induced colitis, but not gastritis, as shown by an increase in the disease activity score and the colonic myeloperoxidase content. In the brain, EE enhanced the WAS-induced activation of the dentate gyrus and unmasked an inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression within this part of the hippocampus. Conversely, EE inhibited the WAS-evoked activation of the central amygdala and prevented the inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression in this region. EE, in addition, blunted the WAS-induced activation of the infralimbic cortex and attenuated the inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression in this area. These data reveal that EE has a region-specific effect on stress-induced c-Fos expression in the corticolimbic system, which is likely to improve stress resilience. The response of the prefrontal cortex - amygdala - hippocampus circuitry to psychological stress is also modified by the systemic stress of gut inflammation, and this interaction between external

  9. Roles of Endoplasmic Reticulum Stress in NECA-Induced Cardioprotection against Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Fengmei Xing

    2017-01-01

    Full Text Available Objective. This study aimed to investigate whether the nonselective A2 adenosine receptor agonist NECA induces cardioprotection against myocardial ischemia/reperfusion (I/R injury via glycogen synthase kinase 3β (GSK-3β and the mitochondrial permeability transition pore (mPTP through inhibition of endoplasmic reticulum stress (ERS. Methods and Results. H9c2 cells were exposed to H2O2 for 20 minutes. NECA significantly prevented H2O2-induced TMRE fluorescence reduction, indicating that NECA inhibited the mPTP opening. NECA blocked H2O2-induced GSK-3β phosphorylation and GRP94 expression. NECA increased GSK-3β phosphorylation and decreased GRP94 expression, which were prevented by both ERS inductor 2-DG and PKG inhibitor KT5823, suggesting that NECA may induce cardioprotection through GSK-3β and cGMP/PKG via ERS. In isolated rat hearts, both NECA and the ERS inhibitor TUDCA decreased myocardial infarction, increased GSK-3β phosphorylation, and reversed GRP94 expression at reperfusion, suggesting that NECA protected the heart by inhibiting GSK-3β and ERS. Transmission electron microscopy showed that NECA and TUDCA reduced mitochondrial swelling and endoplasmic reticulum expansion, further supporting that NECA protected the heart by preventing the mPTP opening and ERS. Conclusion. These data suggest that NECA prevents the mPTP opening through inactivation of GSK-3β via ERS inhibition. The cGMP/PKG signaling pathway is responsible for GSK-3β inactivation by NECA.

  10. FMRFamide signaling promotes stress-induced sleep in Drosophila.

    Science.gov (United States)

    Lenz, Olivia; Xiong, Jianmei; Nelson, Matthew D; Raizen, David M; Williams, Julie A

    2015-07-01

    Enhanced sleep in response to cellular stress is a conserved adaptive behavior across multiple species, but the mechanism of this process is poorly understood. Drosophila melanogaster increases sleep following exposure to septic or aseptic injury, and Caenorhabditis elegans displays sleep-like quiescence following exposure to high temperatures that stress cells. We show here that, similar to C. elegans, Drosophila responds to heat stress with an increase in sleep. In contrast to Drosophila infection-induced sleep, heat-induced sleep is not sensitive to the time-of-day of the heat pulse. Moreover, the sleep response to heat stress does not require Relish, the NFκB transcription factor that is necessary for infection-induced sleep, indicating that sleep is induced by multiple mechanisms from different stress modalities. We identify a sleep-regulating role for a signaling pathway involving FMRFamide neuropeptides and their receptor FR. Animals mutant for either FMRFamide or for the FMRFamide receptor (FR) have a reduced recovery sleep in response to heat stress. FR mutants, in addition, show reduced sleep responses following infection with Serratia marcescens, and succumb to infection at a faster rate than wild-type controls. Together, these findings support the hypothesis that FMRFamide and its receptor promote an adaptive increase in sleep following stress. Because an FMRFamide-like neuropeptide plays a similar role in C. elegans, we propose that FRMFamide neuropeptide signaling is an ancient regulator of recovery sleep which occurs in response to cellular stress. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Effect of sardine proteins on hyperglycaemia, hyperlipidaemia and lecithin:cholesterol acyltransferase activity, in high-fat diet-induced type 2 diabetic rats.

    Science.gov (United States)

    Benaicheta, Nora; Labbaci, Fatima Z; Bouchenak, Malika; Boukortt, Farida O

    2016-01-14

    Type 2 diabetes (T2D) is a major risk factor of CVD. The effects of purified sardine proteins (SP) were examined on glycaemia, insulin sensitivity and reverse cholesterol transport in T2D rats. Rats fed a high-fat diet (HFD) for 5 weeks, and injected with a low dose of streptozotocin, were used. The diabetic rats were divided into four groups, and they were fed casein (CAS) or SP combined with 30 or 5% lipids, for 4 weeks. HFD-induced hyperglycaemia, insulin resistance and hyperlipidaemia in rats fed HFD, regardless of the consumed protein. In contrast, these parameters lowered in rats fed SP combined with 5 or 30% lipids, and serum insulin values reduced in SP v. CAS. HFD significantly increased total cholesterol and TAG concentrations in the liver and serum, whereas these parameters decreased with SP, regardless of lipid intake. Faecal cholesterol excretion was higher with SP v. CAS, combined with 30 or 5% lipids. Lecithin:cholesterol acyltransferase (LCAT) activity and HDL3-phospholipids (PL) were higher in CAS-HF than in CAS, whereas HDL2-cholesteryl esters (CE) were lower. Otherwise, LCAT activity and HDL2-CE were higher in the SP group than in the CAS group, whereas HDL3-PL and HDL3-unesterified cholesterol were lower. Moreover, LCAT activity lowered in the SP-HF group than in the CAS-HF group, when HDL2-CE was higher. In conclusion, these results indicate the potential effects of SP to improve glycaemia, insulin sensitivity and reverse cholesterol transport, in T2D rats.

  12. Cholesterol facilitates interactions between α-synuclein oligomers and charge-neutral membranes

    DEFF Research Database (Denmark)

    van Maarschalkerweerd, Andreas; Vetri, Valeria; Vestergaard, Bente

    2015-01-01

    composed of anionic lipids, while the more physiologically relevant zwitterionic lipids remain intact. We present experimental evidence for significant morphological changes in zwitterionic membranes containing cholesterol, induced by α-synuclein oligomers. Depending on the lipid composition, model...... of cholesterol for mediating interactions between physiologically relevant membranes and α-synuclein....

  13. Cholesterol-lowing effect of taurine in HepG2 cell.

    Science.gov (United States)

    Guo, Junxia; Gao, Ya; Cao, Xuelian; Zhang, Jing; Chen, Wen

    2017-03-16

    A number of studies indicate that taurine promotes cholesterol conversion to bile acids by upregulating CYP7A1 gene expression. Few in vitro studies are concerned the concentration change of cholesterol and its product of bile acids, and the molecular mechanism of CYP7A1 induction by taurine. The levels of intracellular total cholesterol (TC), free cholesterol (FC), cholesterol ester (EC), total bile acids (TBA) and medium TBA were determined after HepG2 cells were cultured for 24/48 h in DMEM supplemented with taurine at the final concentrations of 1/10/20 mM respectively. The protein expressions of CYP7A1, MEK1/2, c-Jun, p-c-Jun and HNF-4α were detected. Taurine significantly reduced cellular TC and FC in dose -and time-dependent ways, and obviously increased intracellular/medium TBA and CYP7A1 expressions. There was no change in c-Jun expression, but the protein expressions of MEK1/2 and p-c-Jun were increased at 24 h and inhibited at 48 h by 20 mM taurine while HNF4α was induced after both of the 24 h and 48 h treatment. Taurine could enhance CYP7A1 expression by inducing HNF4α and inhibiting MEK1/2 and p-c-Jun expressions to promote intracellular cholesterol metabolism.

  14. Ropivacaine and Bupivacaine prevent increased pain sensitivity without altering neuroimmune activation following repeated social defeat stress.

    Science.gov (United States)

    Sawicki, Caroline M; Kim, January K; Weber, Michael D; Jarrett, Brant L; Godbout, Jonathan P; Sheridan, John F; Humeidan, Michelle

    2018-03-01

    Liposomal Bupivacaine did not develop mechanical allodynia following exposure to stress, but did develop social avoidance behavior. Neither drug affected stress-induced activation of monocytes in the bone marrow, blood, or brain. Neuroinflammatory responses developed in all treatment groups, as evidenced by elevated IL-1β mRNA levels in the brain and spinal cord after RSD. In this study, psychosocial stress was associated with increased pain sensitivity in mice. Development of mechanical allodynia with RSD was blocked by regional analgesia with local anesthetics, Ropivacaine or Liposomal Bupivacaine. Despite blocking mechanical allodynia, these anesthetic interventions did not prevent neuroimmune activation or social avoidance associated with RSD. These data suggest that stress-induced neuroinflammatory changes are not associated with increased sensitivity to pain following RSD. Thus, blocking peripheral nociception was effective in inhibiting enhanced pain signaling without altering stress-induced immune or behavioral responses. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Administration of the TrkB receptor agonist 7,8-dihydroxyflavone prevents traumatic stress-induced spatial memory deficits and changes in synaptic plasticity.

    Science.gov (United States)

    Sanz-García, Ancor; Knafo, Shira; Pereda-Pérez, Inmaculada; Esteban, José A; Venero, César; Armario, Antonio

    2016-09-01

    Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations and it is characterized by cognitive deficits that include impaired explicit memory. The neurobiological bases of such PTSD-associated memory alterations are yet to be elucidated and no satisfactory treatment for them exists. To address this issue, we first studied whether a single exposure of young adult rats (60 days) to immobilization on boards (IMO), a putative model of PTSD, produces long-term behavioral effects (2-8 days) similar to those found in PTSD patients. Subsequently, we investigated whether the administration of the TrkB agonist 7,8-dihydroxyflavone (DHF) 8 h after stress (therapeutic window) ameliorated the PTSD-like effect of IMO and the associated changes in synaptic plasticity. A single IMO exposure induced a spatial memory impairment similar to that found in other animal models of PTSD or in PTSD patients. IMO also increased spine density and long-term potentiation (LTP) in the CA3-CA1 pathway. Significantly, DHF reverted both spatial memory impairment and the increase in LTP, while it produced no effect in the controls. These data provide novel insights into the possible neurobiological substrate for explicit memory impairment in PTSD patients, supporting the idea that the activation of the BDNF/TrkB pathway fulfils a protective role after severe stress. Administration of DHF in the aftermath of a traumatic experience might be relevant to prevent its long-term consequences. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Sodium Butyrate Induces Endoplasmic Reticulum Stress and Autophagy in Colorectal Cells: Implications for Apoptosis.

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    Jintao Zhang

    (siRNA targeting BIP and CHOP methods, the induction of BIP, PDI, IRE1a, and LC3-II was blocked, but PARP cleavage was markedly enhanced.Taken together, these results suggested that sodium butyrate-induced autophagy was mediated by endoplasmic reticulum stress, and that preventing autophagy by blocking the endoplasmic reticulum stress response enhanced sodium butyrate-induced apoptosis. These results provide novel insights into the anti-tumor mechanisms of butyric acid.

  17. Ameliorative Effect of Hexane Extract of Phalaris canariensis on High Fat Diet-Induced Obese and Streptozotocin-Induced Diabetic Mice

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    Rosa Martha Perez Gutierrez

    2014-01-01

    Full Text Available Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect of Phalaris canariensis seeds hexane extract (Al-H in high-fat diet- (HFD- induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD and severely diabetic (SD mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis.

  18. Ameliorative Effect of Hexane Extract of Phalaris canariensis on High Fat Diet-Induced Obese and Streptozotocin-Induced Diabetic Mice.

    Science.gov (United States)

    Perez Gutierrez, Rosa Martha; Madrigales Ahuatzi, Diana; Horcacitas, Maria Del Carmen; Garcia Baez, Efren; Cruz Victoria, Teresa; Mota-Flores, Jose Maria

    2014-01-01

    Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect of Phalaris canariensis seeds hexane extract (Al-H) in high-fat diet- (HFD-) induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD) and severely diabetic (SD) mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis.

  19. Plasma lipid oxidation predicts atherosclerotic status better than cholesterol in diabetic apolipoprotein E deficient mice

    DEFF Research Database (Denmark)

    Petersen, Karen Ekkelund; Lykkesfeldt, Jens; Raun, Kirsten

    2017-01-01

    Increased levels of oxidative stress have been suggested to play a detrimental role in the development of diabetes-related vascular complications. Here, we investigated whether the concentration of malondialdehyde, a marker of lipid oxidation correlated to the degree of aortic plaque lesions...... in a proatherogenic diabetic mouse model. Three groups of apolipoprotein E knockout mice were studied for 20 weeks, a control, a streptozotocin-induced diabetic, and a diabetic enalapril-treated group. Enalapril was hypothesized to lower oxidative stress level and thus the plaque burden. Both diabetic groups were...... significantly different from the control group as they had higher blood glucose, HbA1c, total cholesterol, low-density lipoprotein, very low-density lipoprotein, together with a lower high-density lipoprotein concentration and body weight. Animals in the diabetic group had significantly higher plaque area...

  20. Chronic administration of mitochondrion-targeted peptide SS-31 prevents atherosclerotic development in ApoE knockout mice fed Western diet.

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    Meng Zhang

    Full Text Available Oxidative stress and inflammatory factors are deeply involved in progression of atherosclerosis. Mitochondrion-targeted peptide SS-31, selectively targeting to mitochondrial inner membrane reacting with cardiolipin, has been reported to inhibit ROS generation and mitigate inflammation. The present study was designed to investigate whether SS-31 could suppress the development of atherosclerosis in vivo.Male ApoE-/- mice (8 weeks old fed with Western diet were treated with normal saline or SS-31 (1 mg/kg/d or 3 mg/kg/d through subcutaneous injection for 12 weeks. Oil Red O staining was performed to evaluate area and sizes of the plaques. DHE staining and immunohistochemical staining of 8-OHDG was performed to assess the oxidative stress. The aorta ATP contents were assessed by the ATP bioluminescence assay kit. Immunohistochemical staining of CD68 and α-SMA and Masson's trichrome staining were performed to evaluate the composition of atherosclerotic plaque. Biochemical assays were performed to determine the protein level and activity of superoxide dismutase (SOD. The levels of CD36, LOX-1 and ABCA1 were immunohistochemically and biochemically determined to evaluate the cholesterol transport in aorta and peritoneal macrophages. Inflammatory factors, including ICAM-1, MCP-1, IL-6 and CRP in serum, were detected through ELISA.SS-31 administration reduced the area and sizes of western diet-induced atherosclerotic plaques and changed the composition of the plaques in ApoE-/- mice. Oxidative stress was suppressed, as evidenced by the reduced DHE stain, down-regulated 8-OHDG expression, and increased SOD activity after chronic SS-31 administration. Moreover, systemic inflammation was ameliorated as seen by decreasing serum ICAM-1, MCP-1, and IL-6 levels. Most importantly, SS-31 administration inhibited cholesterol influx by down-regulating expression of CD36 and LOX-1 to prevent lipid accumulation to further suppress the foam cell formation and