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Sample records for antioxidant n-acetyl-l-cysteine ameliorates

  1. Effects of N-acetyl-L-cysteine on gene expression of antioxidant enzymes in yeast cells after irradiation

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    Kim, Jin Kyu; Park, Ji Young; Ryu, Tae Ho; Roh, Chang Hyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain)

    2012-04-15

    Ionizing radiation induces water radiolysis, which generates highly reactive hydroxyl radicals. Reactive oxygen species (ROS) cause apoptosis and cell damage. When exposed to ionizing radiation, cells activates ROS scavenging detoxifying enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase. SOD scavenges superoxide radicals by catalyzing the conversion of two of these radicals into hydrogen peroxide and molecular oxygen. The hydrogen peroxide formed by superoxide dismutase and by other processes is scavenged by catalase, a ubiquitous heme protein that catalyzes the dismutation of hydrogen peroxide into water and molecular oxygen. Yeast has two catalase and three GPx proteins. The biochemical function of GPx is to reduce lipid-hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water. N-acetylL-cysteine (NAC) having a thiol, a precursor for glutathione (GSH), is known as one of the antioxidants. NAC prevents the depletion of GSH by radiation, increases the production of GSH, and improves enzymes activity and alkaline phosphatase. In this study, the role of NAC as an antioxidant and a radioprotector was examined on cell survival, transcriptional level, and protein level. through observing viability of cells, analyzing the gene expression of antioxidant enzyme, measuring the SOD activity and intracellular GSH levels in yeast W303-1A strain The cell viability of haploid S. cerevisiae W303-1A strain was reduced significantly at the low dose (10∼30 Gy). The half-lethal dose of the strain was about 20 Gy. The CFU assay result confirmed that NAC could not rescue the cells from radiation-induced death. When irradiated with 100 Gy, an increase in the transcriptional expression was observed in the antioxicant genes. The expression of these genes decreased by treatment of NAC in irradiated cells. NAC decline SOD activity and intracellular GSH levels. The present study shows that NAC can directly scavenge

  2. Effect of N-Acetyl-L-Cysteine and alpha-Tocopherol Administration on Endogenous Antioxidant Protection of Liver DNA and RNA and plasma Lipid Profile in gamma-Irradiated Rats

    International Nuclear Information System (INIS)

    Abou-Safi, H.M.; Ashry, O.M.; Kafafy, Y.A.

    2005-01-01

    The present study wasundertaken to evaluate the combined antioxidative capacity of N-acetyl-L-cysteine (NAC, 120 mg/100g b. wt) and alpha tocopherol (10mg/100g b. wt.) injected intra peritoneally one h before irradiation of male rats. Whole body gamma irradiation (2Gy) induced significant elevation in liver DNA and significant drop in liver protein content, while liver RNA showed no significant changes. Triglycerides and LDL-cholesterol elevated significantly after irradiation, whereas no significant changes were observed in total cholesterol, while HDL-cholesterol significantly decreased. Blood and liver glutathione were significantly decreased, whereas plasma MDA was significantly increased. NAC and alpha-tocopherol injection elevated RNA and blood glutathione levels compared to control and depressed total cholesterol and LDL-cholesterol levels, as well as MDA in the liver. The combined treatment prior to irradiation decreased DNA, elevated RNA and normalized liver protein content. Triglycerides were decreased after 1 and 3 days and total cholesterol dropped significantly on the 1 st and 7 th days. LDL was ameliorated while HDL was significantly declined then elevated after 7 days. Blood glutathione was normalized while liver glutathione was significantly elevated and MDA was reduced both in liver and plasma. This combined treatment has proven to be recommended to enhance the natural defenses against deleterious effects of oxidative stress

  3. Lifespan extension and increased resistance to environmental stressors by N-Acetyl-L-Cysteine in Caenorhabditis elegans

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    Seung-Il Oh

    2015-05-01

    Full Text Available OBJECTIVE: This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans. METHOD: The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV, was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment. RESULTS: Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment. CONCLUSION: N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors.

  4. Thiol-redox antioxidants protect against lung vascular endothelial cytoskeletal alterations caused by pulmonary fibrosis inducer, bleomycin: comparison between classical thiol-protectant, N-acetyl-l-cysteine, and novel thiol antioxidant, N,N′-bis-2-mercaptoethyl isophthalamide

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    Patel, Rishi B.; Kotha, Sainath R.; Sauers, Lynn A.; Malireddy, Smitha; Gurney, Travis O.; Gupta, Niladri N.; Elton, Terry S.; Magalang, Ulysses J.; Marsh, Clay B.; Haley, Boyd E.; Parinandi, Narasimham L.

    2012-01-01

    Lung vascular alterations and pulmonary hypertension associated with oxidative stress have been reported to be involved in idiopathic lung fibrosis (ILF). Therefore, here, we hypothesize that the widely used lung fibrosis inducer, bleomycin, would cause cytoskeletal rearrangement through thiol-redox alterations in the cultured lung vascular endothelial cell (EC) monolayers. We exposed the monolayers of primary bovine pulmonary artery ECs to bleomycin (10 µg) and studied the cytotoxicity, cytoskeletal rearrangements, and the macromolecule (fluorescein isothiocyanate-dextran, 70,000 mol. wt.) paracellular transport in the absence and presence of two thiol-redox protectants, the classic water-soluble N-acetyl-l-cysteine (NAC) and the novel hydrophobic N,N′-bis-2-mercaptoethyl isophthalamide (NBMI). Our results revealed that bleomycin induced cytotoxicity (lactate dehydrogenase leak), morphological alterations (rounding of cells and filipodia formation), and cytoskeletal rearrangement (actin stress fiber formation and alterations of tight junction proteins, ZO-1 and occludin) in a dose-dependent fashion. Furthermore, our study demonstrated the formation of reactive oxygen species, loss of thiols (glutathione, GSH), EC barrier dysfunction (decrease of transendothelial electrical resistance), and enhanced paracellular transport (leak) of macromolecules. The observed bleomycin-induced EC alterations were attenuated by both NAC and NBMI, revealing that the novel hydrophobic thiol-protectant, NBMI, was more effective at µM concentrations as compared to the water-soluble NAC that was effective at mM concentrations in offering protection against the bleomycin-induced EC alterations. Overall, the results of the current study suggested the central role of thiol-redox in vascular EC dysfunction associated with ILF. PMID:22409285

  5. In vitro effect of N-acetyl-L-cysteine on glutathione and sulfhydryl levels in X-linked adrenoleukodystrophy patients

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    Desirèe Padilha Marchetti

    2017-04-01

    Full Text Available Introduction: Recent evidence shows that oxidative stress seems to be related with the pathophysiology of X-linked adrenoleukodystrophy (X-ALD, a neurodegenerative disorder. Methods: In the present study, the in vitro effect of N-acetyl-L-cysteine (NAC on glutathione (GSH and sulfhydryl levels in X-ALD patients was evaluated. Results: A significant reduction of GSH and sulfhydryl content was observed in X-ALD patients compared to the control group. Furthermore, 5 mM of NAC, in vitro, led to an increase in GSH content and sulfhydryl groups in these patients. Conclusion: These data probably indicate that an adjuvant therapy with the antioxidant NAC could improve the oxidative imbalance in X-ALD patients. Keywords: X- linked adrenoleukodystrophy; N-acetyl-L-cysteine; glutathione; sulfhydryl

  6. N-acetyl-L-cysteine protects dental tissue stem cells against oxidative stress in vitro.

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    Martacic, Jasmina; Filipovic, Milica Kovacevic; Borozan, Suncica; Cvetkovic, Zorica; Popovic, Tamara; Arsic, Aleksandra; Takic, Marija; Vucic, Vesna; Glibetic, Maria

    2018-02-15

    The aim of our study was to investigate whether N-acetyl-L-cysteine (NAC) could protect stem cells from exfoliated deciduous teeth (SHED) against oxidative damage, during in vitro cultivation, to preserve regenerative potential of these cells. Accordingly, we examined the potential of cell culture supplementation with NAC in prevention of lipid peroxidation, unfavorable changes of total lipids fatty acid composition, and the effects on the activity of antioxidant enzymes. We analyzed the extent of oxidative damage in SHED after 48 h treatment with different NAC concentrations. Cellular lipid peroxidation was determined upon reaction with thiobarbituric acid. All enzyme activities were measured spectrophotometrically, based on published methods. Fatty acid methyl esters were analyzed by gas-liquid chromatography. Concentration of 0.1 mM NAC showed the most profound effects on SHED, significantly decreasing levels of lipid peroxidation in comparison to control. This dose also diminished the activities of antioxidant enzymes. Furthermore, NAC treatment significantly changed fatty acid composition of cells, reducing levels of oleic acid and monounsaturated fatty acids and increasing linoleic acid, n-6, and total polyunsaturated fatty acid (PUFA) proportions. Low dose of NAC significantly decreased lipid peroxidation and altered fatty acid composition towards increasing PUFA. The reduced oxidative damage of cellular lipids could be strongly related to improved SHED survival in vitro. Low doses of antioxidants, applied during stem cells culturing and maintenance, could improve cellular characteristics in vitro. This is prerequisite for successful use of stem cells in various clinical applications.

  7. [N-acetyl-L-cysteine reduces the ozone-induced lung inflammation response in mice].

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    Chen, Qing-Zi; Fu, Zhao-Di; Zhou, Yu-Bo; Zhou, Li-Fen; Yang, Chun-Tao; Li, Jian-Hua

    2016-12-25

    In this study, we investigated the protective effect of the antioxidant N-acetyl-L-cysteine (NAC) on the lung inflammation caused by ozone (O 3 ) exposure in mice. Thirty-two C57BL/6 mice were randomly divided into control group, O 3 group, O 3 +NAC group and NAC group. Mice were exposed to O 3 (1.0 ppm) or fresh air for 3 h on the day 1, day 3 and day 5, respectively. NAC (100 mg/kg) was intraperitoneally applied to the mice 1 h before each exposure. At 24 h after the 3-time exposure, the alveolar wall structure was severely damaged and the infiltrated inflammatory cells were apparent perivascularly and peribronchiolarly. Significant increases in the total white blood cell count, macrophage, lymphocyte and neutrophil counts, as well as total protein concentration were observed in the bronchoalveolar lavage fluid (BALF) (P mice (P mice. The beneficial effect of NAC might be related with the p38 MAPK and NF-κB p65 signal pathway.

  8. The effect of N-acetyl-L-cysteine on the viscosity of ileal neobladder mucus.

    NARCIS (Netherlands)

    Schrier, B.P.; Lichtendonk, W.J.; Witjes, J.A.

    2002-01-01

    N-acetyl-L-cysteine (NAC) proved to be an effective mucolytic in pulmonary secretions. Our goal was to investigate the in vitro effect of NAC on viscosity of ileal neobladder mucus. The urine of a patient with an ileal neobladder was collected during the first 7 days postoperatively and stored in a

  9. ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors.

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    Halasi, Marianna; Wang, Ming; Chavan, Tanmay S; Gaponenko, Vadim; Hay, Nissim; Gartel, Andrei L

    2013-09-01

    NAC (N-acetyl-L-cysteine) is commonly used to identify and test ROS (reactive oxygen species) inducers, and to inhibit ROS. In the present study, we identified inhibition of proteasome inhibitors as a novel activity of NAC. Both NAC and catalase, another known scavenger of ROS, similarly inhibited ROS levels and apoptosis associated with H₂O₂. However, only NAC, and not catalase or another ROS scavenger Trolox, was able to prevent effects linked to proteasome inhibition, such as protein stabilization, apoptosis and accumulation of ubiquitin conjugates. These observations suggest that NAC has a dual activity as an inhibitor of ROS and proteasome inhibitors. Recently, NAC was used as a ROS inhibitor to functionally characterize a novel anticancer compound, piperlongumine, leading to its description as a ROS inducer. In contrast, our own experiments showed that this compound depicts features of proteasome inhibitors including suppression of FOXM1 (Forkhead box protein M1), stabilization of cellular proteins, induction of ROS-independent apoptosis and enhanced accumulation of ubiquitin conjugates. In addition, NAC, but not catalase or Trolox, interfered with the activity of piperlongumine, further supporting that piperlongumine is a proteasome inhibitor. Most importantly, we showed that NAC, but not other ROS scavengers, directly binds to proteasome inhibitors. To our knowledge, NAC is the first known compound that directly interacts with and antagonizes the activity of proteasome inhibitors. Taken together, the findings of the present study suggest that, as a result of the dual nature of NAC, data interpretation might not be straightforward when NAC is utilized as an antioxidant to demonstrate ROS involvement in drug-induced apoptosis.

  10. N-Acetyl-L-cysteine inhibits sulfur mustard-induced and TRPA1-dependent calcium influx.

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    Stenger, Bernhard; Popp, Tanja; John, Harald; Siegert, Markus; Tsoutsoulopoulos, Amelie; Schmidt, Annette; Mückter, Harald; Gudermann, Thomas; Thiermann, Horst; Steinritz, Dirk

    2017-05-01

    Transient receptor potential family channels (TRPs) have been identified as relevant targets in many pharmacological as well as toxicological studies. TRP channels are ubiquitously expressed in different tissues and act among others as sensors for different external stimuli, such as mechanical stress or noxious impacts. Recent studies suggest that one member of this family, the transient receptor potential ankyrin 1 cation channel (TRPA1), is involved in pain, itch, and various diseases, suggesting TRPA1 as a potential therapeutic target. As a nociceptor, TRPA1 is mainly activated by noxious or electrophilic compounds, including alkylating substances. Previous studies already revealed an impact of 2-chloroethyl-ethyl sulfide on the ion channel TRPA1. In this study, we demonstrate that sulfur mustard (bis-(2-chloroethyl) sulfide, SM) activates the human TRPA1 (hTRPA1) in a dose-dependent manner measured by the increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ). Besides that, SM-induced toxicity was attenuated by antioxidants. However, very little is known about the underlying mechanisms. Here, we demonstrate that N-acetyl-L-cysteine (NAC) prevents SM-induced hTRPA1-activation. HEK293-A1-E cells, overexpressing hTRPA1, show a distinct increase in [Ca 2+ ] i immediately after SM exposure, whereas this increase is reduced in cells pretreated with NAC in a dose-dependent manner. Interestingly, glutathione, although being highly related to NAC, did not show an effect on hTRPA1 channel activity. Taken together, our results provide evidence that SM-dependent activation of hTRPA1 can be diminished by NAC treatment, suggesting a direct interaction of NAC and the hTRPA1 cation channel. Our previous studies already showed a correlation of hTRPA1-activation with cell damage after exposure to alkylating agents. Therefore, NAC might be a feasible approach mitigating hTRPA1-related dysregulations after exposure to SM.

  11. A Preliminary Study: N-acetyl-L-cysteine Improves Semen Quality following Varicocelectomy

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    Foroogh Barekat

    2016-05-01

    Full Text Available Background: Surgery is considered the primary treatment for male infertility from clinical varicocele. One of the main events associated with varicocele is excessive production of reactive oxygen species (ROS. N-acetyl-L-cysteine (NAC, an antioxidant that scavenges free radicals, is considered a supplement to alleviate glutathione (GSH depletion during oxidative stress. Despite beneficial effects of NAC in other pathological events, there is no report on the effect of NAC in individuals with varicocele. Therefore, the aim of this study is to evaluate the outcome of NAC on semen quality, protamine content, DNA damage, oxidative stress and fertility following varicocelectomy. Materials and Methods: This prospective clinical trial included 35 infertile men with varicocele randomly divided into control (n=20 and NAC (n=15 groups. We assessed semen parameters, protamine content [chromomycin A3 (CMA3], DNA integrity [terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL] and oxidative stress [2', 7'-dichlorodihydrofluorescein-diacetate (DCFH-DA] before and three months after varicocelectomy. Results: Percentage of abnormal semen parameters, protamine deficiency, DNA fragmentation and oxidative stress were significantly decreased in both groups compared to before surgery. We calculated the percentage of improvement in these parameters compared to before surgery for each group, then compared the results between the groups. Only percentage of protamine deficiency and DNA fragmentation significantly differed between the NAC and control groups. Conclusion: The results of this study, for the first time, revealed that NAC improved chromatin integrity and pregnancy rate when administered as adjunct therapy post-varicocelectomy (Registeration Number: IRCT201508177223N5.

  12. N-acetyl-L-cysteine protects against inhaled sulfur mustard poisoning in the large swine.

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    Jugg, B; Fairhall, S; Smith, A; Rutter, S; Mann, T; Perrott, R; Jenner, J; Salguero, J; Shute, J; Sciuto, A M

    2013-05-01

    Sulfur mustard is a blister agent that can cause death by pulmonary damage. There is currently no effective treatment. N-acetyl-L-cysteine (NAC) has mucolytic and antioxidant actions and is an important pre-cursor of cellular glutathione synthesis. These actions may have potential to reduce mustard-induced lung injury. Evaluate the effect of nebulised NAC as a post-exposure treatment for inhaled sulfur mustard in a large animal model. Fourteen anesthetized, surgically prepared pigs were exposed to sulfur mustard vapor (100 μg.kg⁻¹), 10 min) and monitored, spontaneously breathing, to 12 h. Control animals had no further intervention (n = 6). Animals in the treatment group were administered multiple inhaled doses of NAC (1 ml of 200 mg.ml⁻¹ Mucomyst™ at + 30 min, 2, 4, 6, 8, and 10 h post-exposure, n = 8). Cardiovascular and respiratory parameters were recorded. Arterial blood was collected for blood gas analysis while blood and bronchoalveolar lavage fluid were collected for hematology and inflammatory cell analysis. Urine was collected to detect a sulfur mustard breakdown product. Lung tissue samples were taken for histopathological and post-experimental analyses. Five of six sulfur mustard-exposed animals survived to 12 h. Arterial blood oxygenation (PaO₂) and saturation levels were significantly decreased at 12 h. Arterial blood carbon dioxide (PaCO₂) significantly increased, and arterial blood pH and bicarbonate (HCO₃⁻) significantly decreased at 12 h. Shunt fraction was significantly increased at 12 h. In the NAC-treated group all animals survived to 12 h (n = 8). There was significantly improved arterial blood oxygen saturation, HCO₃⁻ levels, and shunt fraction compared to those of the sulfur mustard controls. There were significantly fewer neutrophils and lower concentrations of protein in lavage compared to sulfur mustard controls. NAC's mucolytic and antioxidant properties may be responsible for the beneficial effects seen, improving

  13. Interactions between N-acetyl-L-cysteine protected CdTe quantum dots and doxorubicin through spectroscopic method

    International Nuclear Information System (INIS)

    Yang, Xiupei; Lin, Jia; Liao, Xiulin; Zong, Yingying; Gao, Huanhuan

    2015-01-01

    Highlights: • CdTe quantum dots with the diameter of 3–5 nm were synthesized in aqueous solution. • The modified CdTe quantum dots showed well fluorescence properties. • The interaction between the CdTe quantum dots and doxorubicin (DR) was investigated. - Abstract: N-acetyl-L-cysteine protected cadmium telluride quantum dots with a diameter of 3–5 nm were synthesized in aqueous solution. The interaction between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin was investigated by ultraviolet–visible absorption and fluorescence spectroscopy at physiological conditions (pH 7.2, 37 °C). The results indicate that electron transfer has occurred between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin under light illumination. The quantum dots react readily with doxorubicin to form a N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex via electrostatic attraction between the −NH 3 + moiety of doxorubicin and the −COO − moiety of N-acetyl-L-cysteine/cadmium telluride quantum dots. The interaction of N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex with bovine serum albumin was studied as well, showing that the complex might induce the conformation change of bovine serum due to changes in microenvironment of bovine serum

  14. N-Acetyl-l-cysteine effects on multi-species oral biofilm formation and bacterial ecology.

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    Rasmussen, K; Nikrad, J; Reilly, C; Li, Y; Jones, R S

    2016-01-01

    Future therapies for the treatment of dental decay have to consider the importance of preserving bacterial ecology while reducing biofilm adherence to teeth. A multi-species plaque-derived (MSPD) biofilm model was used to assess how concentrations of N-acetyl-l-cysteine (NAC) (0, 0·1, 1, 10%) affected the growth of complex oral biofilms. Biofilms were grown (n = 96) for 24 h on hydroxyapatite discs in BMM media with 0·5% sucrose. Bacterial viability and biomass formation was examined on each disc using a microtitre plate reader. In addition, fluorescence microscopy and Scanning Electron Microscopy was used to qualitatively examine the effect of NAC on bacterial biofilm aggregation, extracellular components and bacterial morphology. The total biomass was significantly decreased after exposure of both 1% (from 0·48, with a 95% confidence interval of (0·44, 0·57) to 0·35, with confidence interval (0·31, 0·38)) and 10% NAC (0·14 with confidence interval (0·11, 0·17)). 16S rRNA amplicon sequencing analysis indicated that 1% NAC reduced biofilm adherence while preserving biofilm ecology. As a compound with a wide safety margin, N-acetyl-l-cysteine (NAC) has the potential to be used as a long term anti-plaque bacteriostatic agent for managing chronic dental decay without substantially altering biofilm's bacterial ecology. The potential anti-caries benefit of NAC is directly related to reducing the biofilm coverage which reduces the degree of acid generation and the amount of time that the surface is exposed to a lower pH. © 2015 The Society for Applied Microbiology.

  15. Effects of N-acetyl-L-cysteine on renal haemodynamics and function in early ischaemia-reperfusion injury in rats.

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    Nitescu, Nicoletta; Grimberg, Elisabeth; Ricksten, Sven-Erik; Guron, Gregor

    2006-01-01

    1. Renal ischaemia-reperfusion (IR) severely compromises kidney function and has been shown to cause persistent abnormalities in intrarenal blood flow. The aim of the present study was to examine whether N-acetyl-L-cysteine (NAC), a thiol-containing anti-oxidant, improves renal haemodynamics and function during early reperfusion in rats subjected to renal IR. 2. Male Sprague-Dawley rats were divided into groups receiving either isotonic saline (IR-Saline; n = 8) or NAC (IR-NAC; n = 8) prior to (200 mg/kg, i.p., 24 and 12 h before acute experimentation) and during acute renal clearance experiments (bolus 150 mg/kg followed by a continuous infusion of 43 mg/kg per h, i.v.). During acute experimentation, thiobutabarbital-anaesthetized rats were subjected to a right-sided nephrectomy, followed by left kidney IR (40 min renal artery occlusion). Left kidney function and blood flow and intrarenal cortical and outer medullary perfusion measured by laser-Doppler flowmetry was analysed at baseline, during ischaemia and for 80 min of reperfusion. 3. Renal IR produced an approximate 85% reduction in glomerular filtration rate (GFR) and a pronounced increase in fractional urinary sodium excretion, throughout reperfusion, with no statistically significant differences between groups. 4. During reperfusion, total renal blood flow and cortical and outer medullary perfusion rapidly returned to levels not significantly different from baseline in both groups. The relative increase in renal vascular resistance in response to IR was more pronounced in NAC-treated rats compared with saline-treated animals (P < 0.05). 5. In conclusion, treatment with NAC did not improve kidney function during the first 80 min after renal IR. In addition, the marked reduction in GFR following reperfusion was not associated with any detectable abnormalities in intrarenal perfusion.

  16. Protective Effects of N-Acetyl-L-cystein on 3,4-Methylene Dioxymethamphetamie-Induced Neurotoxicity in Cerebellum of Male Rats

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    Sara Soleimani Asl

    2011-10-01

    Full Text Available Introduction: 3-4, methylenedioxymethamphetamine (MDMA causes apoptosis in nervous system and several studies suggest that oxidative stress contributes to MDMA-induced neurotoxicity. The aim of this study is to examine the effects of N-acetyl-L-Cystein (NAC as an antioxidant on MDMA-induced apoptosis. Methods: 21 Sprague dawley male rats (200-250mg were treated with MDMA (2×0,5mg/kg or MDMA plus NAC (100mg/kg IP for 7 day. After last administration of MDMA, rats were killed, cerebellum was removed and Bax and Bcl-2 expression was assessed by western blotting method. Results: The results of this study showed that MDMA causes up-regulation of Bax and down-regulation of Bcl-2 and NAC administration attenuated MDMA-induced apoptosis. Discussion: The present study suggests that NAC treatment may improve MDMA-induced neurotoxicity.

  17. Protective Effects of N-Acetyl-L-cystein on 3,4-Methylene Dioxymethamphetamie-Induced Neurotoxicity in Cerebellum of Male Rats

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    Sara Soleimani Asl

    2011-10-01

    Full Text Available Objective(s: 3-4, methylenedioxymethamphetamine (MDMA causes apoptosis in nervous system and several studies suggest that oxidative stress contributes to MDMA-induced neurotoxicity. The aim of this study is to examine the effects of N-acetyl-L-Cystein (NAC as an antioxidant on MDMA-induced apoptosis. Materials and Methods: 21 Sprague dawley male rats (200-250mg were treated with MDMA (2×0,5mg/kg or MDMA plus NAC (100mg/kg IP for 7 day. After last administration of MDMA, rats were killed, cerebellum was removed and Bax and Bcl-2 expression was assessed by western blotting method. Results: The results of this study showed that MDMA causes up-regulation of Bax and down-regulation of Bcl-2 and NAC administration attenuated MDMA-induced apoptosis. Conclusion: The present study suggests that NAC treatment may improve MDMA-induced neurotoxicity.

  18. Long-time treatment by low-dose N-acetyl-L-cysteine enhances proinflammatory cytokine expressions in LPS-stimulated macrophages.

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    Tomokazu Ohnishi

    Full Text Available N-acetyl-L-cysteine is known to act as a reactive oxygen species scavenger and used in clinical applications. Previous reports have shown that high-dose N-acetyl-L-cysteine treatment inhibits the expression of proinflammatory cytokines in activated macrophages. Here, we have found that long-time N-acetyl-L-cysteine treatment at low-concentration increases phosphorylation of extracellular signal-regulated kinase 1/2 and AKT, which are essential for the induction of proinflammatory cytokines including interleukin 1β and interleukin 6 in lipopolysaccharide-stimulated RAW264.7 cells. Furthermore, long-time N-acetyl-L-cysteine treatment decreases expressions of protein phosphatases, catalytic subunit of protein phosphatase-2A and dual specificity phosphatase 1. On the other hand, we have found that short-time N-acetyl-L-cysteine treatment at low dose increases p53 expression, which inhibits expressions of proinflammatory cytokines. These observations suggest that long-time low-dose N-acetyl-L-cysteine treatment increases expressions of proinflammatory cytokines through enhancement of kinase phosphorylation.

  19. Protective effects of deferasirox and N-acetyl-L-cysteine on iron overload-injured bone marrow

    OpenAIRE

    Shen, J.C.; Zhang, Y.C.; Zhao, M.F.

    2017-01-01

    Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX) and N-acetyl-L-cysteine (NAC) on injured bone marrow hematopoietic stem/progenitor cells (HSPC) induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe) model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC), and the function of HSPCs was then examined. Iron overload mark...

  20. Comparative effects of N-acetyl-L-cysteine and ramipril on arterial hypertension, insulin resistance, and oxidative stress in chronically glucose-fed rats.

    Science.gov (United States)

    El Midaoui, Adil; Ismael, Mahmoud Ali; Lu, Huogen; Fantus, I George; de Champlain, Jacques; Couture, Réjean

    2008-11-01

    Beneficial effects of an antioxidant (N-acetyl-L-cysteine, NAC) and an angiotensin I-converting enzyme (ACE) inhibitor (ramipril) were assessed in a rat model of insulin resistance induced by 10% glucose feeding for 20 weeks. Treatments with NAC (2 g/kg per day) and ramipril (1 mg/kg per day) were initiated at 16 weeks in the drinking fluid. Systolic blood pressure, plasma levels of insulin and glucose, and insulin resistance were significantly higher in rats treated with glucose for 20 weeks. This was associated with a higher production of superoxide anion and NADPH oxidase activity in aorta and liver and with a marked reduction in protein expression of skeletal muscle insulin receptor substrate-1 (IRS-1) in the gastrocnemius muscle. NAC prevented all these alterations. Although ramipril also reversed high blood pressure, it had a lesser effect on insulin resistance (including IRS-1) and blocked superoxide anion production only in aorta. Ramipril, in contrast to NAC, did not reduce NADPH oxidase activity in aorta and liver or plasma levels of 4-hydroxynonenal and malondialdehyde. Results suggest that the inhibition of the oxidative stress in hypertensive and insulin-resistant states contributes to the therapeutic effects of NAC and ramipril. Whereas NAC exerts effective antioxidant activity in multiple tissues, ramipril appears to preferentially target the vasculature.

  1. Protective effects of deferasirox and N-acetyl-L-cysteine on iron overload-injured bone marrow

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    Shen, J.C.; Zhang, Y.C.; Zhao, M.F.

    2017-01-01

    Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX) and N-acetyl-L-cysteine (NAC) on injured bone marrow hematopoietic stem/progenitor cells (HSPC) induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe) model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC), and the function of HSPCs was then examined. Iron overload markedly decreased the number of murine HSPCs in bone marrow. Subsequent colony-forming cell assays showed that iron overload also decreased the colony forming capacity of HSPCs, the effect of which could be reversed by DFX and NAC. The bone marrow hematopoiesis damage caused by iron overload could be alleviated by DFX and NAC. PMID:29069221

  2. Protective effects of deferasirox and N-acetyl-L-cysteine on iron overload-injured bone marrow

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    J.C. Shen

    2017-10-01

    Full Text Available Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX and N-acetyl-L-cysteine (NAC on injured bone marrow hematopoietic stem/progenitor cells (HSPC induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC, and the function of HSPCs was then examined. Iron overload markedly decreased the number of murine HSPCs in bone marrow. Subsequent colony-forming cell assays showed that iron overload also decreased the colony forming capacity of HSPCs, the effect of which could be reversed by DFX and NAC. The bone marrow hematopoiesis damage caused by iron overload could be alleviated by DFX and NAC.

  3. Cadmium-induced oxidative damage and protective effects of N-acetyl-L-cysteine against cadmium toxicity in Solanum nigrum L

    International Nuclear Information System (INIS)

    Deng Xiaopeng; Xia Yan; Hu Wei; Zhang Hongxiao; Shen Zhenguo

    2010-01-01

    The effects of cadmium (Cd) on the accumulation of hydrogen peroxide (H 2 O 2 ) and antioxidant enzyme activities in roots of Solanum nigrum L. and the role of N-acetyl-L-cysteine (NAC) as a cysteine (Cys) donor against Cd toxicity were investigated. Cd at 50 and 200 μM significantly increased the contents of thiobarbituric acid-reactive substances (TBARS), the production of H 2 O 2 and superoxide anion (O 2 · - ), and the activities of catalase, guaiacol peroxidase, ascorbate peroxidase, glutathione peroxidase (GSH-Px), glutathione reductase, and superoxide dismutase. Experiments with diphenylene iodonium as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and NaN 3 as an inhibitor of peroxidase showed that the major source of Cd-induced reactive oxygen species in the roots may include plasma membrane-bound NADPH oxidase and peroxidase. In addition, the effects of NAC on plant growth, antioxidant enzyme activity, and non-protein thiol content were analyzed. Under Cd stress, the addition of 500 μM NAC decreased the contents of TBARS and production of H 2 O 2 and O 2 · - , but increased levels of Cys and reduced glutathione (GSH), phytochelatins, and activity of GSH-Px in roots. These results suggest that NAC could protect plants from oxidative stress damage, and this protection seems to be performed via increased GSH biosynthesis. Furthermore, NAC treatment also increased the contents of protein thiols in S. nigrum roots. By using size-exclusion chromatography, we found involvement of NAC in the Cd tolerance mechanism through increased biosynthesis of Cd-binding proteins.

  4. Cadmium-induced oxidative damage and protective effects of N-acetyl-L-cysteine against cadmium toxicity in Solanum nigrum L

    Energy Technology Data Exchange (ETDEWEB)

    Deng Xiaopeng; Xia Yan; Hu Wei [College of Life Sciences, Nanjing Agricultural University, Weigang 1, Nanjing 210095 (China); Zhang Hongxiao, E-mail: hxzhang@njau.edu.cn [College of Life Sciences, Nanjing Agricultural University, Weigang 1, Nanjing 210095 (China); Shen Zhenguo, E-mail: zgshen@njau.edu.cn [College of Life Sciences, Nanjing Agricultural University, Weigang 1, Nanjing 210095 (China)

    2010-08-15

    The effects of cadmium (Cd) on the accumulation of hydrogen peroxide (H{sub 2}O{sub 2}) and antioxidant enzyme activities in roots of Solanum nigrum L. and the role of N-acetyl-L-cysteine (NAC) as a cysteine (Cys) donor against Cd toxicity were investigated. Cd at 50 and 200 {mu}M significantly increased the contents of thiobarbituric acid-reactive substances (TBARS), the production of H{sub 2}O{sub 2} and superoxide anion (O{sub 2}{center_dot}{sup -}), and the activities of catalase, guaiacol peroxidase, ascorbate peroxidase, glutathione peroxidase (GSH-Px), glutathione reductase, and superoxide dismutase. Experiments with diphenylene iodonium as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and NaN{sub 3} as an inhibitor of peroxidase showed that the major source of Cd-induced reactive oxygen species in the roots may include plasma membrane-bound NADPH oxidase and peroxidase. In addition, the effects of NAC on plant growth, antioxidant enzyme activity, and non-protein thiol content were analyzed. Under Cd stress, the addition of 500 {mu}M NAC decreased the contents of TBARS and production of H{sub 2}O{sub 2} and O{sub 2}{center_dot}{sup -}, but increased levels of Cys and reduced glutathione (GSH), phytochelatins, and activity of GSH-Px in roots. These results suggest that NAC could protect plants from oxidative stress damage, and this protection seems to be performed via increased GSH biosynthesis. Furthermore, NAC treatment also increased the contents of protein thiols in S. nigrum roots. By using size-exclusion chromatography, we found involvement of NAC in the Cd tolerance mechanism through increased biosynthesis of Cd-binding proteins.

  5. Dual effects of N-acetyl-L-cysteine dependent on NQO1 activity: suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity.

    Science.gov (United States)

    Toyooka, Tatsushi; Shinmen, Takuya; Aarts, Jac M M J G; Ibuki, Yuko

    2012-11-01

    A typical antioxidant, N-acetyl-L-cysteine (NAC) generally protects cells from oxidative damage induced by reactive oxygen species (ROS). 9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, produces ROS in redox cycling following two-electron reduction by NAD(P)H:quinone oxidoreductase 1 (NQO1), which has been considered as a cause of its cyto- and genotoxicity. In this study, we show that NAC unexpectedly augments the toxicity of 9,10-PQ in cells with low NQO1 activity. In four human skin cell lines, the expression and the activity of NQO1 were lower than in human adenocarcinoma cell lines, A549 and MCF7. In the skin cells, the cytotoxicity of 9,10-PQ was significantly enhanced by addition of NAC. The formation of DNA double strand breaks accompanying phosphorylation of histone H2AX, was also remarkably augmented. On the other hand, the cyto- and genotoxicity were suppressed by addition of NAC in the adenocarcinoma cells. Two contrasting experiments: overexpression of NQO1 in CHO-K1 cells which originally expressed low NQO1 levels, and knock-down of NQO1 in the adenocarcinoma cell line A549 by transfection of RNAi, also showed that NAC suppressed 9,10-PQ-induced toxicity in cell lines expressing high NQO1 activity and enhanced it in cell lines with low NQO1 activity. The results suggested that dual effects of NAC on the cyto- and genotoxicity of 9,10-PQ were dependent on tissue-specific NQO1 activity. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. N-Acetyl-L-Cysteine Affords Protection against Lead-Induced Cytotoxicity and Oxidative Stress in Human Liver Carcinoma (HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2007-06-01

    Full Text Available Although lead exposure has declined in recent years as a result of change to lead-free gasoline, several epidemiological have pointed out that it represents a medical and public health emergency, especially in young children consuming high amounts of lead-contaminated flake paints. A previous study in our laboratory indicated that lead exposure induces cytotoxicity in human liver carcinoma cells. In the present study, we evaluated the role of oxidative stress in lead-induced toxicity, and the protective effect of the anti-oxidant n-acetyl-l-cysteine (NAC. We hypothesized that oxidative stress plays a role in lead-induced cytotoxicity, and that NAC affords protection against this adverse effect. To test this hypothesis, we performed the MTT [3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide] assay and the trypan blue exclusion test for cell viability. We also performed the thiobarbituric acid test for lipid peroxidation. Data obtained from the MTT assay indicated that NAC significantly increased the viability of HepG2 cells in a dosedependent manner upon 48 hours of exposure. Similar trend was obtained with the trypan blue exclusion test. Data generated from the thiobarbituric acid test showed a significant (p ≤ 0.05 increase of MDA levels in lead nitrate-treated HepG2 cells compared to control cells. Interestingly, the addition of NAC to lead nitrate-treated HepG2 cells significantly decreased cellular content of reactive oxygen species (ROS, as evidenced by the decrease in lipid peroxidation byproducts. Overall, findings from this study suggest that NAC inhibits lead nitrate-induced cytotoxicity and oxidative stress in HepG2 cells. Hence, NAC may be used as a salvage therapy for lead-induced toxicity in exposed persons.

  7. Facile synthesis of N-acetyl-L-cysteine capped CdHgSe quantum dots and selective determination of hemoglobin.

    Science.gov (United States)

    Wang, Qingqing; Zhan, Guoqing; Li, Chunya

    2014-01-03

    Using N-acetyl-L-cysteine (NAC) as a stabilizer, well water-dispersed, high-quality and stable CdHgSe quantum dots were facilely synthesized via a simple aqueous phase method. The as-prepared NAC capped CdHgSe quantum dots were thoroughly characterized by fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy and transmission electron microscopy. A novel method for the selective determination of hemoglobin (Hb) was developed based on fluorescence quenching of the NAC capped CdHgSe quantum dots. A number of key factors including pH value of phosphate buffer solution, quantum dots concentration, the adding sequence of reagents and reaction time that influence the analytical performance of the NAC capped CdHgSe quantum dots in Hb determination were investigated. Under the optimal experimental conditions, the change of fluorescence intensity (ΔI) was linearly proportional to the concentration of Hb in the range of 4.0×10(-9)-4.4×10(-7) mol L(-1) with a detection limit of 2.0×10(-9) mol L(-1). The developed method has been successfully employed to determine Hb in human urine samples. Copyright © 2013. Published by Elsevier B.V.

  8. Effects of N-acetyl-L-cysteine on the membrane vesicle release and growth of respiratory pathogens.

    Science.gov (United States)

    Volgers, Charlotte; Benedikter, Birke J; Grauls, Gert E; Hellebrand, Pauline H M; Savelkoul, Paul H M; Stassen, Frank R M

    2017-05-01

    Bacterial infections contribute to the disease progression of chronic obstructive pulmonary disease by stimulating mucus production in the airways. This increased mucus production and other symptoms are often alleviated when patients are treated with mucolytics such as N-acetyl-L-cysteine (NAC). Moreover, NAC has been suggested to inhibit bacterial growth. Bacteria can release membrane vesicles (MVs) in response to stress, and recent studies report a role for these proinflammatory MVs in the pathogenesis of airways disease. Yet, until now it is not clear whether NAC also affects the release of these MVs. This study set out to determine whether NAC, at concentrations reached during high-dose nebulization, affects bacterial growth and MV release of the respiratory pathogens non-typeable Haemophilus influenzae (NTHi), Moraxella catarrhalis (Mrc), Streptococcus pneumoniae (Spn) and Pseudomonas aeruginosa (Psa). We observed that NAC exerted a strong bacteriostatic effect, but also induced the release of proinflammatory MVs by NTHi, Mrc and Psa, but not by Spn. Interestingly, NAC also markedly blunted the release of TNF-α by naive macrophages in response to MVs. This suggests that the application of NAC by nebulization at a high dosage may be beneficial for patients with airway conditions associated with bacterial infections. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Spectroscopic investigations on the effect of N-Acetyl-L-cysteine-Capped CdTe Quantum Dots on catalase

    Science.gov (United States)

    Sun, Haoyu; Yang, Bingjun; Cui, Erqian; Liu, Rutao

    2014-11-01

    Quantum dots (QDs) are recognized as some of the most promising semiconductor nanocrystals in biomedical applications. However, the potential toxicity of QDs has aroused wide public concern. Catalase (CAT) is a common enzyme in animal and plant tissues. For the potential application of QDs in vivo, it is important to investigate the interaction of QDs with CAT. In this work, the effect of N-Acetyl-L-cysteine-Capped CdTe Quantum Dots with fluorescence emission peak at 612 nm (QDs-612) on CAT was investigated by fluorescence, synchronous fluorescence, fluorescence lifetime, ultraviolet-visible (UV-vis) absorption and circular dichroism (CD) techniques. Binding of QDs-612 to CAT caused static quenching of the fluorescence, the change of the secondary structure of CAT and the alteration of the microenvironment of tryptophan residues. The association constants K were determined to be K288K = 7.98 × 105 L mol-1 and K298K = 7.21 × 105 L mol-1. The interaction between QDs-612 and CAT was spontaneous with 1:1 stoichiometry approximately. The CAT activity was also inhibited for the bound QDs-612. This work provides direct evidence about enzyme toxicity of QDs-612 to CAT in vitro and establishes a new strategy to investigate the interaction between enzyme and QDs at a molecular level, which is helpful for clarifying the bioactivities of QDs in vivo.

  10. Inhibition of sulfur mustard-increased protease activity by niacinamide, N-acetyl-L-cysteine or dexamethasone

    Energy Technology Data Exchange (ETDEWEB)

    Cowan, F.M.; Broomfield, C.A.; Smith, W.J.

    1991-03-11

    The pathologic mechanism of sulfur mustard-induced skin vesication is as yet undefined. Papirmeister et al. have postulated a biochemical mechanism for sulfur mustard-induced cutaneous injury involving sequelae of DNA alkylation, metabolic disruption resulting in NAD+ depletion and activation of protease. The authors have utilized a chromogenic peptide substrate assay to establish that human peripheral blood lymphocytes exposed 24 hr previously to sulfur mustard exhibited an increase in proteolytic activity. Doses of compounds known to alter the biochemical events associated with sulfur mustard exposure or reduce protease activity were tested in this system for their ability to block the sulfur mustard-induced protease activity. Treatment with niacinamide 1 hr after or with N-acetyl-L-cysteine or dexamethasone 24 hr prior to sulfur mustard exposure resulted in a decrease of 39%, 33% and 42% respectively of sulfur mustard-increased protease activity. These data suggest that therapeutic intervention into the biochemical pathways that culminate in protease activation might serve as an approach to treatment of sulfur mustard-induced pathology.

  11. Fluorescent sensor for selective determination of copper ion based on N-acetyl-L-cysteine capped CdHgSe quantum dots.

    Science.gov (United States)

    Wang, Qingqing; Yu, Xiangyang; Zhan, Guoqing; Li, Chunya

    2014-04-15

    Using N-acetyl-L-cysteine as a stabilizer, well water-dispersed, high-quality and stable CdHgSe quantum dots were facilely synthesized via a simple aqueous phase method. The as-prepared N-acetyl-L-cysteine capped CdHgSe quantum dots were thoroughly characterized by transmission electron microscopy, X-ray diffraction spectroscopy and FTIR. A fluorescent sensor for selective determination of copper ions was developed using N-acetyl-L-cysteine capped CdHgSe quantum dots as fluorescent probe. The fluorescence intensity of N-acetyl-L-cysteine capped CdHgSe quantum dots decreased when interacted with copper ions due to the formation of coordination complex and aggregates. The method possesses high selectivity and is not influenced by some potential interferences such as Ag(+), Zn(2+), Co(2+) and Ni(2+). Under the optimal conditions, the change of fluorescence intensity (ΔI) was linearly proportional to the concentration of copper ions in the range of 1.0×10(-9)-4.0×10(-7) mol L(-1), with a detection limit as low as 2.0×10(-10) mol L(-1) (S/N=3). The developed method had been successfully employed to determine Cu(2+) in shrimp and South-lake water samples, and the results were verified by atomic absorption spectroscopy. The fluorescent sensor was demonstrated to be selective, sensitive and simple for copper ion determination, and promise for practical applications. © 2013 Published by Elsevier B.V.

  12. Global gene expression analysis in time series following N-acetyl L-cysteine induced epithelial differentiation of human normal and cancer cells in vitro

    International Nuclear Information System (INIS)

    Gustafsson, Anna C; Parasassi, Tiziana; Lundeberg, Joakim; Kupershmidt, Ilya; Edlundh-Rose, Esther; Greco, Giulia; Serafino, Annalucia; Krasnowska, Eva K; Lundeberg, Thomas; Bracci-Laudiero, Luisa; Romano, Maria-Concetta

    2005-01-01

    Cancer prevention trials using different types of antioxidant supplements have been carried out at several occasions and one of the investigated compounds has been the antioxidant N-acetyl-L-cysteine (NAC). Studies at the cellular level have previously demonstrated that a single supplementation of NAC induces a ten-fold more rapid differentiation in normal primary human keratinocytes as well as a reversion of a colon carcinoma cell line from neoplastic proliferation to apical-basolateral differentiation [1]. The investigated cells showed an early change in the organization of the cytoskeleton, several newly established adherens junctions with E-cadherin/β-catenin complexes and increased focal adhesions, all features characterizing the differentiation process. In order to investigate the molecular mechanisms underlying the proliferation arrest and accelerated differentiation induced by NAC treatment of NHEK and Caco-2 cells in vitro, we performed global gene expression analysis of NAC treated cells in a time series (1, 12 and 24 hours post NAC treatment) using the Affymetrix GeneChip™ Human Genome U95Av2 chip, which contains approximately 12,000 previously characterized sequences. The treated samples were compared to the corresponding untreated culture at the same time point. Microarray data analysis revealed an increasing number of differentially expressed transcripts over time upon NAC treatment. The early response (1 hour) was transient, while a constitutive trend was commonly found among genes differentially regulated at later time points (12 and 24 hours). Connections to the induction of differentiation and inhibition of growth were identified for a majority of up- and down-regulated genes. All of the observed transcriptional changes, except for seven genes, were unique to either cell line. Only one gene, ID-1, was mutually regulated at 1 hour post treatment and might represent a common mediator of early NAC action. The detection of several genes that

  13. Global gene expression analysis in time series following N-acetyl L-cysteine induced epithelial differentiation of human normal and cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Bracci-Laudiero Luisa

    2005-07-01

    Full Text Available Abstract Background Cancer prevention trials using different types of antioxidant supplements have been carried out at several occasions and one of the investigated compounds has been the antioxidant N-acetyl-L-cysteine (NAC. Studies at the cellular level have previously demonstrated that a single supplementation of NAC induces a ten-fold more rapid differentiation in normal primary human keratinocytes as well as a reversion of a colon carcinoma cell line from neoplastic proliferation to apical-basolateral differentiation 1. The investigated cells showed an early change in the organization of the cytoskeleton, several newly established adherens junctions with E-cadherin/β-catenin complexes and increased focal adhesions, all features characterizing the differentiation process. Methods In order to investigate the molecular mechanisms underlying the proliferation arrest and accelerated differentiation induced by NAC treatment of NHEK and Caco-2 cells in vitro, we performed global gene expression analysis of NAC treated cells in a time series (1, 12 and 24 hours post NAC treatment using the Affymetrix GeneChip™ Human Genome U95Av2 chip, which contains approximately 12,000 previously characterized sequences. The treated samples were compared to the corresponding untreated culture at the same time point. Results Microarray data analysis revealed an increasing number of differentially expressed transcripts over time upon NAC treatment. The early response (1 hour was transient, while a constitutive trend was commonly found among genes differentially regulated at later time points (12 and 24 hours. Connections to the induction of differentiation and inhibition of growth were identified for a majority of up- and down-regulated genes. All of the observed transcriptional changes, except for seven genes, were unique to either cell line. Only one gene, ID-1, was mutually regulated at 1 hour post treatment and might represent a common mediator of early NAC

  14. The influence of N-acetyl-L-cysteine on oxidative stress and nitric oxide synthesis in stimulated macrophages treated with a mustard gas analogue

    Directory of Open Access Journals (Sweden)

    Smith Milton

    2008-06-01

    Full Text Available Abstract Background Sulphur mustard gas, 2, 2'-dichlorodiethyl sulphide (HD, is a chemical warfare agent. Both mustard gas and its monofunctional analogue, 2-chloroethyl ethyl sulphide (CEES, are alkylating agents that react with and diminish cellular thiols and are highly toxic. Previously, we reported that lipopolysaccharide (LPS significantly enhances the cytotoxicity of CEES in murine RAW 264.7 macrophages and that CEES transiently inhibits nitric oxide (NO production via suppression of inducible NO synthase (iNOS protein expression. NO generation is an important factor in wound healing. In this paper, we explored the hypotheses that LPS increases CEES toxicity by increasing oxidative stress and that treatment with N-acetyl-L-cysteine (NAC would block LPS induced oxidative stress and protect against loss of NO production. NAC stimulates glutathione (GSH synthesis and also acts directly as a free radical scavenger. The potential therapeutic use of the antibiotic, polymyxin B, was also evaluated since it binds to LPS and could thereby block the enhancement of CEES toxicity by LPS and also inhibit the secondary infections characteristic of HD/CEES wounds. Results We found that 10 mM NAC, when administered simultaneously or prior to treatment with 500 μM CEES, increased the viability of LPS stimulated macrophages. Surprisingly, NAC failed to protect LPS stimulated macrophages from CEES induced loss of NO production. Macrophages treated with both LPS and CEES show increased oxidative stress parameters (cellular thiol depletion and increased protein carbonyl levels. NAC effectively protected RAW 264.7 cells simultaneously treated with CEES and LPS from GSH loss and oxidative stress. Polymyxin B was found to partially block nitric oxide production and diminish CEES toxicity in LPS-treated macrophages. Conclusion The present study shows that oxidative stress is an important mechanism contributing to CEES toxicity in LPS stimulated macrophages and

  15. Dual effects of N-acetyl-L-cysteine dependent on NQO1 activity: Suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Toyooka, Tatsushi; Shinmen, Takuya [Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka (Japan); Aarts, Jac M.M.J.G. [Division of Toxicology, Wageningen University, Wageningen (Netherlands); Ibuki, Yuko, E-mail: ibuki@u-shizuoka-ken.ac.jp [Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka (Japan)

    2012-11-01

    A typical antioxidant, N-acetyl-L-cysteine (NAC) generally protects cells from oxidative damage induced by reactive oxygen species (ROS). 9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, produces ROS in redox cycling following two-electron reduction by NAD(P)H:quinone oxidoreductase 1 (NQO1), which has been considered as a cause of its cyto- and genotoxicity. In this study, we show that NAC unexpectedly augments the toxicity of 9,10-PQ in cells with low NQO1 activity. In four human skin cell lines, the expression and the activity of NQO1 were lower than in human adenocarcinoma cell lines, A549 and MCF7. In the skin cells, the cytotoxicity of 9,10-PQ was significantly enhanced by addition of NAC. The formation of DNA double strand breaks accompanying phosphorylation of histone H2AX, was also remarkably augmented. On the other hand, the cyto- and genotoxicity were suppressed by addition of NAC in the adenocarcinoma cells. Two contrasting experiments: overexpression of NQO1 in CHO-K1 cells which originally expressed low NQO1 levels, and knock‐down of NQO1 in the adenocarcinoma cell line A549 by transfection of RNAi, also showed that NAC suppressed 9,10-PQ-induced toxicity in cell lines expressing high NQO1 activity and enhanced it in cell lines with low NQO1 activity. The results suggested that dual effects of NAC on the cyto- and genotoxicity of 9,10-PQ were dependent on tissue-specific NQO1 activity. -- Highlights: ► NAC augmented the cytotoxicity of 9,10-PQ in skin cell lines. ► 9,10-PQ-induced DSBs accompanying γ-H2AX were also augmented by NAC. ► NAC suppressed the cyto- and genotoxicity of 9,10-PQ in adenocarcinoma cell lines. ► The dual effects of NAC on toxicity of 9,10-PQ were dependent on NQO1 activity.

  16. Amelioration Strategies Fail To Prevent Tobacco Smoke Effects On Neurodifferentiation: Nicotinic Receptor Blockade, Antioxidants, Methyl Donors

    Science.gov (United States)

    Slotkin, Theodore A.; Skavicus, Samantha; Card, Jennifer; Levin, Edward D.; Seidler, Frederic J.

    2015-01-01

    Tobacco smoke exposure is associated with neurodevelopmental disorders. We used neuronotypic PC12 cells to evaluate the mechanisms by which tobacco smoke extract (TSE) affects neurodifferentiation. In undifferentiated cells, TSE impaired DNA synthesis and cell numbers to a much greater extent than nicotine alone; TSE also impaired cell viability to a small extent. In differentiating cells, TSE enhanced cell growth at the expense of cell numbers and promoted emergence of the dopaminergic phenotype. Nicotinic receptor blockade with mecamylamine was ineffective in preventing the adverse effects of TSE and actually enhanced the effect of TSE on the dopamine phenotype. A mixture of antioxidants (Vitamin C, Vitamin E, N-acetyl-L-cysteine) provided partial protection against cell loss but also promoted loss of the cholinergic phenotype in response to TSE. Notably, the antioxidants themselves altered neurodifferentiation, reducing cell numbers and promoting the cholinergic phenotype at the expense of the dopaminergic phenotype, an effect that was most prominent for N-acetyl-L-cysteine. Treatment with methyl donors (Vitamin B12, folic acid, choline) had no protectant effect and actually enhanced the cell loss evoked by TSE; they did have a minor, synergistic interaction with antioxidants protecting against TSE effects on growth. Thus, components of tobacco smoke perturb neurodifferentiation through mechanisms that cannot be attributed to the individual effects of nicotine, oxidative stress or interference with one-carbon metabolism. Consequently, attempted amelioration strategies may be partially effective at best, or, as seen here, can actually aggravate injury interfering with normal developmental signals and/or by sensitizing cells to TSE effects on neurodifferentiation. PMID:25891525

  17. Differences in quantification of DNA double-strand breaks assessed by 53BP1/γH2AX focus formation assays and the comet assay in mammalian cells treated with irradiation and N-acetyl-L-cysteine

    International Nuclear Information System (INIS)

    Kurashige, Tomomi; Shimamura, Mika; Nagayama, Yuji

    2016-01-01

    The biological effect of ionizing radiation (IR) on genomic DNA is thought to be either direct or indirect; the latter is mediated by IR induction of free radicals and reactive oxygen species (ROS). This study was designed to evaluate the effect of N-acetyl-L-cysteine (NAC), a well-known ROS-scavenging antioxidant, on IR induction of genotoxicity, cytotoxicity and ROS production in mammalian cells, and aimed to clarify the conflicting data in previous publications. Although we clearly demonstrate the beneficial effect of NAC on IR-induced genotoxicity and cytotoxicity (determined using the micronucleus assay and cell viability/clonogenic assays), the data on NAC's effect on DNA double-strand break (DSB) formation were inconsistent in different assays. Specifically, mitigation of IR-induced DSBs by NAC was readily detected by the neutral comet assay, but not by the γH2AX or 53BP1 focus assays. NAC is a glutathione precursor and exerts its effect after conversion to glutathione, and presumably it has its own biological activity. Assuming that the focus assay reflects the biological responses to DSBs (detection and repair), while the comet assay reflects the physical status of genomic DNA, our results indicate that the comet assay could readily detect the antioxidant effect of NAC on DSB formation. However, NAC's biological effect might affect the detection of DSB repair by the focus assays. Our data illustrate that multiple parameters should be carefully used to analyze DNA damage when studying potential candidates for radioprotective compounds

  18. The effect of N-acetyl-l-cysteine and ascorbic acid on visible-light-irradiated camphorquinone/N,N-dimethyl-p-toluidine-induced oxidative stress in two immortalized cell lines.

    Science.gov (United States)

    Pagoria, D; Geurtsen, W

    2005-11-01

    Recent studies have revealed that visible-light (VL)-irradiated camphorquinone (CQ), in the presence of a tertiary amine (e.g., N,N-dimethyl-p-toluidine, DMT), generates initiating radicals that may indiscriminately react with molecular oxygen forming reactive oxygen species (ROS). In this study, the ability of the antioxidants N-acetyl-l-cysteine (NAC) and ascorbic acid (AA) to reduce intracellular oxidative stress induced by VL-irradiated CQ/DMT or VL-irradiated hydrogen peroxide (H(2)O(2)) was assessed in an immortalized Murine cementoblast cell line (OCCM.30) and an immortalized Murine fibroblast cell line, 3T3-Swiss albino (3T3). Intracellular oxidative stress was measured with the membrane permeable dye, 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCF-DA). VL-irradiated CQ/DMT and VL-irradiated H(2)O(2) each produced significantly (p<0.001) elevated intracellular oxidative levels in both cell types compared to intracellular ROS levels in VL-irradiated untreated cells. OCCM.30 cementoblasts were found to be almost twice as sensitive to VL-irradiated CQ/DMT and VL-irradiated H(2)O(2) treatment compared to 3T3 fibroblasts. Furthermore, 10mm NAC and 10mm AA each eliminated oxidative stress induced by VL-irradiated CQ/DMT and VL-irradiated H(2)O(2) in both cell types. Our results suggest that NAC and AA may effectively reduce or eliminate oxidative stress in cells exposed to VL-irradiated CQ/DMT following polymerization.

  19. Expression of Genes Related to Oxidative Stress in Yeast Treated with Ionizing Radiation and N-acetyl -L-cysteine

    International Nuclear Information System (INIS)

    Park, Ji Young; Kim, Jin Kyu; Nili, Mohammad

    2010-01-01

    Ionizing radiation (IR) induces water radiolysis, which generates highly reactive hydroxyl radicals. Reactive oxygen species (ROS) cause apoptosis and cell damage including DNA strand breaks (DSBs), base damage, protein damage and lipid-hydroperoxide. Detoxifying enzymes are immediately triggered for ROS scavenging. Yeast contains two forms of superoxide dismutase (SOD). SOD1 as a cytosolic copper-zinc superoxide dismutase is located in the cytoplasm and cytosol. SOD2 as a manganese containing enzyme is act in mitochondria matrix and mitochondrion. These enzymes scavenge superoxide radicals by catalyzing the conversion of two of these radicals into hydrogen peroxide and molecular oxygen. The hydrogen peroxide formed by superoxide dismutase and by other processes is scavenged by catalase, a ubiquitous heme protein that catalyzes the dismutation of hydrogen peroxide into water and molecular oxygen. Yeast contains two catalases. Catalase A (CTA1) and Cytosolic catalase T (CTT1) is located in peroxisome and cytoplasm, respectively. Yeast has two glutathione (GSH) peroxidases, which are GPX1 and GPX2. GPX1 and GPX2 are component of cellular component and cytoplasm, respectively. The biochemical function of GSH peroxidase is to reduce lipid-hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water. Otherwise, chemicals and materials help ROS detoxification against oxidative damage. N-acetyl-Lcysteine (NAC) having a thiol, a precursor for glutathione (GSH), is known as one of the antioxidants. In this study, we examined the effect of NAC through gene expressions related to protective enzyme against oxidative stress in yeast

  20. Insights into the effect of N-acetyl-L-cysteine-capped CdTe quantum dots on the structure and activity of human serum albumin by spectroscopic techniques

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Haoyu; Yang, Xudan; Li, Meng; Han, Songlin; Liu, Yingxue [School of Environmental Science and Engineering, Shandong University, China-America CRC for Environment & Health, Shandong Province, 27# Shanda South Road, Jinan 250100 (China); Tan, Xuejie [School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, Jinan, Shandong Province 250353 (China); Liu, Chunguang, E-mail: chunguangliu2013@sdu.edu.cn [School of Environmental Science and Engineering, Shandong University, China-America CRC for Environment & Health, Shandong Province, 27# Shanda South Road, Jinan 250100 (China); Liu, Rutao [School of Environmental Science and Engineering, Shandong University, China-America CRC for Environment & Health, Shandong Province, 27# Shanda South Road, Jinan 250100 (China)

    2015-11-15

    Quantum dots (QDs) are a kind of nanostructured semiconductor crystals with the size range of 1–10 nm. Their unique photophysical properties and potential toxicity to human health have aroused wide concern of scientists and general public. However, the interaction mechanism of QDs on human serum albumin (HSA, the vital protein in human blood) from both structural and functional perspectives is rarely reported. In the present work, effects of N-acetyl-L-cysteine-capped CdTe quantum dots with fluorescence emission peak at 612 nm (QDs-612) on the conformation and function of HSA were investigated by spectroscopic methods, molecular docking study and esterase activity assay. The hydrophobic interaction between HSA and QDs-612 was spontaneous with the binding constants calculated to be 6.85×10{sup 5} L mol{sup −1} (298 K) and 8.89×10{sup 5} L mol{sup −1} (308 K). The binding of QDs-612 to HSA induced the static quenching of fluorescence and the changes of secondary structure and microenvironment of Tyr-411 residue, which resulted in serious decrease on the hydrolysis of substrate p-nitrophenylacetate in esterase activity assay of HSA. This work confirms the possibility on direct interaction of QDs-612 with HSA and obtains a possible mechanism of relationship between conformation and function of HSA. - Highlights: • The interaction between CdTe QDs (QDs-612) and HSA is spontaneous. • The predominant force of the binding is hydrophobic interaction. • The interaction changes the secondary structure of HSA. • Tyr-411 residue of HSA expose to a hydrophilic environment. • The esterase activity of HSA decreases by adding QDs-612.

  1. Enhanced paracellular and transcellular paclitaxel permeation by chitosan-vitamin E succinate- N-acetyl- l-cysteine copolymer on Caco-2 cell monolayer

    Science.gov (United States)

    Lian, He; Zhang, Tianhong; Sun, Jin; Pu, Xiaohui; Tang, Yilin; Zhang, Youxi; He, Zhonggui

    2014-04-01

    The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan-vitamin E succinate- N-acetyl- l-cysteine (CS-VES-NAC) nanomicelles from the cellular level. In aqueous solution, CS-VES-NAC copolymer self-assembled into the polymeric nanomicelles, with the size ranging from 190 to 240 nm and the drug loading content as high as 20.5 %. Cytotoxicity results showed that the PTX-loaded nanomicelles exhibited the similar effect to PTX solution (PTX-Sol) on Caco-2 cells, but no toxicity observed for blank CS-VES-NAC nanomicelles. The cellular uptake of PTX was significantly increased by CS-VES-NAC nanomicelles, compared with that of PTX-Sol, due to the possible escapement of P-glycoprotein (P-gp) efflux pumps by endocytosis pathway. Confocal laser scanning microscope (CLSM) images also confirmed CS-VES-NAC nanomicelles could be effectively internalized by Caco-2 cells. More importantly, P app value of PTX-loaded CS-VES-NAC nanomicelles was 2.3-fold higher than that of PTX-Sol, and the efflux ratio decreased by more than 10.8-fold for the nanomicelles. As a consequence of opening of tight junctions and P-gp inhibition induced by free CS-VES-NAC copolymer, the P app value of PTX was almost increased up to 19.5-fold. All the results indicate that CS-VES-NAC copolymer hold great promises as nanocarrier for antitumor drug oral delivery by improving paracellular and transcellular permeation.

  2. pH-dependent optical properties of N-acetyl-L-cysteine-capped ZnSe(S) nanocrystals with intense/stable emissions

    Energy Technology Data Exchange (ETDEWEB)

    Soheyli, Ehsan [University of Arak, Department of Physics, Faculty of Science (Iran, Islamic Republic of); Sahraei, Reza, E-mail: r.sahraei@ilam.ac.ir [University of Ilam, Department of Chemistry, Faculty of Science (Iran, Islamic Republic of); Nabiyouni, Gholamreza [University of Arak, Department of Physics, Faculty of Science (Iran, Islamic Republic of)

    2017-03-15

    In the present study, a series of aqueous-based ZnSe(S) nanocrystals (NCs) was prepared at different solution pH ranging from 8 to 11.9, and using N-acetyl-L-cysteine (NAC) as capping agent. In addition to zinc blende structure, the X-ray diffraction studies demonstrated the quantum size regime of the ZnSe(S) NCs. To gain further insight toward the influence of the quantum confinement and pH values on optical properties of the as-prepared NCs, their UV-visible absorption and photoluminescence spectra were systematically analyzed. The absorption spectra experienced a red shift from ~340 to ~382 nm as the pH increased from 8.0 to 11.9, indicating the growth of the as-prepared ZnSe(S) NCs. The emission spectra also show the obvious red shift and the relative area of excitonic to trap emission, firstly increases from pH = 8.0 to 10.7, and then decreases by further increasing of the solution pH. The initial behavior might be due to the improved surface passivation of the trap dangling states by better deprotonation of thiol groups in NAC, whereas at pH >10.7, the faster growth rate of the ZnSe(s) NCs may lead to the formation of many defect sites. All of these phenomena were combined in the scheme which displays the effect of quantum confinement and solution pH on variation of the excitonic and trap-related emissions.

  3. Facile synthesis and characterization of highly fluorescent and biocompatible N-acetyl-L-cysteine capped CdTe/CdS/ZnS core/shell/shell quantum dots in aqueous phase.

    Science.gov (United States)

    Xiao, Qi; Huang, Shan; Su, Wei; Chan, W H; Liu, Yi

    2012-12-14

    The synthesis of water-soluble quantum dots (QDs) in aqueous phase has received much attention recently. To date various kinds of QDs such as CdTe, CdSe, CdTe/CdS and CdSe/ZnS have been synthesized by aqueous methods. However, generally poor-quality QDs (photoluminescent quantum yield (PLQY) lower than 30%) are obtained via this method and the 3-mercaptopropionic acid stabilizer is notorious for its toxicity and awful odor. Here we introduce a novel thiol ligand, N-acetyl-L-cysteine, as an ideal stabilizer that is successfully employed to synthesize high-quality CdTe/CdS/ZnS QDs via a simple aqueous phase. The core/shell/shell structures of the CdTe/CdS/ZnS QDs were verified by x-ray photoelectron spectroscopy, energy dispersive x-ray spectroscopy, x-ray powder diffraction and transmission electron microscopy. These QDs not only possess a high PLQY but also have excellent photostability and favorable biocompatibility, which is vital for many biological applications. This type of water-dispersed QD is a promising candidate for fluorescent probes in biological and medical fields.

  4. N-Acetyl-L-cysteine in the Presence of Cu2+Induces Oxidative Stress and Death of Granule Neurons in Dissociated Cultures of Rat Cerebellum.

    Science.gov (United States)

    Stelmashook, E V; Genrikhs, E E; Kapkaeva, M R; Zelenova, E A; Isaev, N K

    2017-10-01

    Addition into the culture medium of the antioxidant N-acetylcysteine (NAC, 1 mM) in the presence of Cu2+ (0.0005-0.001 mM) induced intensive death of cultured rat cerebellar granule neurons, which was significantly decreased by the zinc ion chelator TPEN (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine). However, the combined action of NAC and Zn2+ did not induce destruction of the neurons. Measurement of the relative intracellular concentration of Zn2+ with the fluorescent probe FluoZin-3 AM or of free radical production using a CellROX Green showed that incubation of the culture for 4 h with Cu2+ and NAC induced an intensive increase in the fluorescence of CellROX Green but not of FluoZin-3. Probably, the protective effect of TPEN in this case could be mediated by its ability to chelate Cu2+. Incubation of cultures in a balanced salt solution in the presence of 0.01 mM Cu2+ caused neuronal death already after 1 h if the NAC concentration in the solution was within 0.005-0.05 mM. NAC at higher concentrations (0.1-1 mM) together with 0.01 mM Cu2+ did not cause the death of neurons. These data imply that the antioxidant NAC can be potentially harmful to neurons even in the presence of nanomolar concentrations of variable valence metals.

  5. Facile synthesis of high-quality water-soluble N-acetyl-L-cysteine-capped Zn(1-x)Cd(x)Se/ZnS core/shell quantum dots emitting in the violet-green spectral range.

    Science.gov (United States)

    Cao, Jie; Xue, Bing; Li, Hui; Deng, Dawei; Gu, Yueqing

    2010-08-15

    In this paper, we report a new facile method to synthesize water-soluble Zn(1-x)Cd(x)Se and core/shell Zn(1-x)Cd(x)Se/ZnS quantum dots (QDs) emitting in the violet-green spectral range, using N-acetyl-L-cysteine (NAC) as a stabilizer. The influence of various experimental variables, including the precursor Zn/Cd/Se/NAC molar ratios, the pH of original solution and the refluxing time on optical properties were explored systematically. The obtained aqueous Zn(1-x)Cd(x)Se QDs exhibit a tunable photoluminescence (PL) emission (from approximately 415 nm to 506 nm) and a favorable narrow PL bandwidth (FWHM: 27-38 nm). After coating with a ZnS shell, the PL emission intensity of the formed core/shell Zn(1-x)Cd(x)Se/ZnS QDs is greatly increased (PL quantum yield (QY): approximately 30%). These resulting Zn(1-x)Cd(x)Se and core/shell Zn(1-x)Cd(x)Se/ZnS QDs were further characterized by transmission electron microscopy (TEM), energy disperse spectroscopy (EDS) and X-ray diffraction (XRD). In addition, the cytotoxicity and the fluorescence imaging of Zn(1-x)Cd(x)Se/ZnS QDs to MCF-7 cells were preliminarily investigated. The experimental results show that the as-prepared violet-green-emitting Zn(1-x)Cd(x)Se/ZnS QDs have low cytotoxicity, which makes them an ideal inorganic fluorescent probe for biolabeling and cell imaging. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Short communication: Application of an N-acetyl-L-cysteine-NaOH decontamination method for the recovery of viable Mycobacterium avium subspecies paratuberculosis from milk of naturally infected cows.

    Science.gov (United States)

    Bradner, L; Robbe-Austerman, S; Beitz, D C; Stabel, J R

    2014-01-01

    Mycobacterium avium ssp. paratuberculosis (MAP) is shed into the milk of cattle affected by Johne's disease and, therefore, is a route of transmission for infection in young stock in dairy herds. The objective of this study was to validate a decontamination and culture protocol for the recovery of MAP from individual bovine milk samples from known infected herds. Decontamination of milk samples (n = 17) with either 0.75% hexadecylpyridinium chloride for 5h or N-acetyl-L-cysteine-1.5% sodium hydroxide (NALC-1.5% NaOH) for 15 min before culture in BACTEC 12 B (Becton Dickinson, Franklin, NJ), para-JEM [Thermo Fisher Scientific (TREK Diagnostic Systems, Inc.), Cleveland, OH], and Herrold's egg yolk (HEY; Becton Dickinson) media was compared. Treatment with NALC-NaOH resulted in a lower percentage (6%) of contaminated samples than did treatment with hexadecylpyridinium chloride (47%), regardless of culture medium. The decontamination protocol (NALC-1.5% NaOH) was then applied to milk samples (n = 144) collected from cows at 7 US dairies. Recovery of viable MAP from the milk samples was low, regardless of culture medium, with recovery from 2 samples cultured in BACTEC 12 B medium, 1 sample cultured in para-JEM medium, and no viable MAP recovered on HEY medium. However, 32 cows were fecal culture positive and 13 milk samples were positive by direct PCR, suggesting that several cows were actively shedding MAP at the time of milk collection. Contamination rates were similar across media, with 39.6, 34.7, and 41.7% of samples contaminated after culture in BACTEC 12 B, para-JEM, and HEY media, respectively. Herd-to-herd variation had a major effect on sample contamination, with the percentage of contaminated samples ranging from 4 to 83%. It was concluded that decontamination of milk with NALC-1.5% NaOH before culture in BACTEC 12 B medium was the most efficacious method for the recovery of viable MAP from milk, although the ability to suppress the growth of contaminating

  7. Effects of L-cysteine and N-acetyl-L-cysteine on 4-hydroxy-2, 5-dimethyl-3(2H)-furanone (furaneol), 5-(hydroxymethyl)furfural, and 5-methylfurfural formation and browning in buffer solutions containing either rhamnose or glucose and arginine.

    Science.gov (United States)

    Haleva-Toledo, E; Naim, M; Zehavi, U; Rouseff, R L

    1999-10-01

    Solutions of L-cysteine (Cys) and N-acetyl-L-cysteine (AcCys), containing glucose or rhamnose, with or without arginine, were buffered to pH 3, 5, and 7 and incubated at 70 degrees C for 48 h. Cys and AcCys inhibited the formation of (hydroxymethyl)furfural (HMF) from glucose and methylfurfural (MF) from rhamnose under acidic conditions. AcCys inhibited the accumulation of 4-hydroxy-2, 5-dimethyl- 3(2H)-furanone (DMHF, Furaneol) from rhamnose, but Cys, under our experimental conditions, enhanced Furaneol accumulation from rhamnose. Cys and AcCys reacted directly with Furaneol but not with HMF or MF. Both Cys and AcCys inhibited nonenzymatic browning at pH 7. At pH 3, however, Cys reacted with both glucose and rhamnose to produce unidentified compounds that increased the visible absorbency.

  8. Ganoderma atrum polysaccharide ameliorates anoxia/reoxygenation-mediated oxidative stress and apoptosis in human umbilical vein endothelial cells.

    Science.gov (United States)

    Zhang, Yan-Song; Li, Wen-Juan; Zhang, Xian-Yi; Yan, Yu-Xin; Nie, Shao-Ping; Gong, De-Ming; Tang, Xiao-Fang; He, Ming; Xie, Ming-Yong

    2017-05-01

    Ganoderma atrum polysaccharide (PSG-1), a main polysaccharide from Ganoderma atrum, possesses potent antioxidant capacity and cardiovascular benefits. The aim of this study was to investigate the role of PSG-1 in oxidative stress and apoptosis in human umbilical vein endothelial cells (HUVECs) under anoxia/reoxygenation (A/R) injury conditions. The results showed that exposure of HUVECs to A/R triggered cell death and apoptosis. Administration of PSG-1 significantly inhibited A/R-induced cell death and apoptosis in HUVECs. PSG-1-reduced A/R injury was mediated via mitochondrial apoptotic pathway, as evidenced by elevation of mitochondrial Bcl-2 protein and mitochondrial membrane potential, and attenuation of Bax translocation, cytochrome c release and caspases activation. Furthermore, PSG-1 enhanced the activities of superoxide dismutase, catalase and glutathione peroxidase and glutathione content, and concomitantly attenuated reactive oxygen species generation, lipid peroxidation and glutathione disulfide content. The antioxidant, N-acetyl-l-cysteine, significantly ameliorated all of these endothelial injuries caused by A/R, suggesting that antioxidant activities might play a key role in PSG-1-induced endothelial protection. Taken together, these findings suggested that PSG-1 could be as a promising adjuvant against endothelial dysfunction through ameliorating oxidative stress and apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Use of antioxidants for the prophylaxis of cold-induced peripheral nerve injury.

    Science.gov (United States)

    Teixeira, Fernanda; Pollock, Martin; Karim, Alveera; Jiang, Yuying

    2002-09-01

    "Trench foot" is a particular risk for those involved in adventure tourism, for soldiers in winter mountain training exercises, and for the homeless. Nonfreezing cold nerve injury is characterized by axonal degeneration, which is attributed to free radicals released during cycles of ischemia and reperfusion. This pilot study sought to determine whether the administration of antioxidants might prevent or ameliorate the development of cold nerve injury. Twenty-six rats were divided into two groups. Group 1 animals received, by gavage, a mixture of vitamin C (150 mg/kg/d), vitamin E (100 mg/kg/d), and N-acetyl-L-cysteine (250 mg/kg/d) daily for 4 weeks. Allopurinol (20 mg/kg/d) was added in the last 4 days of treatment. Group 2 animals served as controls and did not receive any antioxidant supplements. After 1 month, two cycles of sciatic nerve cooling (0 degrees C) were induced in 10 controls and 10 experimental animals using circulating water through a nerve cuff. Six additional control animals were subjected to surgery but did not undergo nerve cooling. All animals were killed on the third postoperative day, and their nerves were processed for ultrastructural and quantitative studies. The proportion of degenerated myelinated and unmyelinated axons showed no significant difference between treated and untreated animals. We conclude that the administration of commonly used antioxidants does not prevent cold nerve injury.

  10. ANTIOXIDANTS AMELIORATION OF ARSENICAL-INDUCED EFFECTS IN VIVO

    Science.gov (United States)

    Antioxidant amelioration of arsenical-induced effects in vivo. ES Hunter and EH Rogers. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC. Antioxidants have been reported to ameliorate the effects of many developmental toxicants. We tested the hypothesis that oxi...

  11. Antioxidants improve mouse preimplantation embryo development and viability.

    Science.gov (United States)

    Truong, Thi T; Soh, Yu May; Gardner, David K

    2016-07-01

    What is the effect of three antioxidants (acetyl-L-carnitine, N-acetyl-L-cysteine and α-lipoic acid), when used individually and in combination, on mouse embryo development in culture, and subsequent fetal development post-transfer? A combination of antioxidants resulted in significant increases in blastocyst cell number, maintained intracellular glutathione (GSH) levels, supported earlier cleavage times from 5-cell stage to expanded blastocyst, and improved fetal developmental irrespective of incubator oxygen concentration. Acetyl-L-carnitine, N-acetyl-L-cysteine and α-lipoic acid have been shown to have beneficial effects individually in several tissues, and most recently on developing embryos, in the presence of oxidative stress. Morphokinetics of mouse embryos were quantitated using time-lapse imaging. GSH levels in pronucleate oocytes were measured. Blastocysts underwent differential nuclear staining for inner cell mass and trophectoderm cells or were transferred to recipient females to assess implantation and fetal development. Pronucleate oocytes from F1 mice were cultured in 5 or 20% oxygen either individually or in groups of 10, in media G1/G2, in the presence or absence of 10 µM acetyl-L-carnitine /10 µM N-acetyl-L-cysteine /5 µM α-lipoic acid, either individually or in combination. Controls were embryos cultured without antioxidants. Intracellular levels of reduced glutathione were quantitated in pronucleate oocytes. Embryo development and viability were analysed through time-lapse microscopy and embryo transfers. Antioxidants significantly increased mouse blastocyst cell numbers compared with control when used individually (Pantioxidants resulted in faster development rates to 5-cell cleavage stage, which continued until the expanded blastocyst stage when cultured in 20% oxygen. The beneficial effects of combining the antioxidants were greater for embryos cultured individually as opposed to in groups of 10 and for those embryos cultured in 20

  12. Amelioration of altered antioxidant status and membrane linked ...

    Indian Academy of Sciences (India)

    However, SOV exerts hypoglycemic effects at relatively high doses with several toxic effects. We used low doses of vanadate in combination with TSP and evaluated their antidiabetic effects on antioxidant enzymes and membrane-linked functions in diabetic rat brains. In rats, diabetes was induced by alloxan monohydrate ...

  13. Ameliorative effect of antioxidants (vitamins C and E against abamectin toxicity in liver, kidney and testis of male albino rats

    Directory of Open Access Journals (Sweden)

    B. Wilson Magdy

    2016-10-01

    In conclusion, it appears that vitamins C and E, or in combination (as antioxidants ameliorate the hepato-renal and testicular toxicity of abamectin, but are not completely protective, especially in liver tissue.

  14. Influence of Different Antioxidants on X-Ray Induced DNA Double-Strand Breaks (DSBs) Using γ-H2AX Immunofluorescence Microscopy in a Preliminary Study.

    Science.gov (United States)

    Brand, Michael; Sommer, Matthias; Ellmann, Stephan; Wuest, Wolfgang; May, Matthias S; Eller, Achim; Vogt, Sabine; Lell, Michael M; Kuefner, Michael A; Uder, Michael

    2015-01-01

    Radiation exposure occurs in X-ray guided interventional procedures or computed tomography (CT) and γ-H2AX-foci are recognized to represent DNA double-strand breaks (DSBs) as a biomarker for radiation induced damage. Antioxidants may reduce the induction of γ-H2AX-foci by binding free radicals. The aim of this study was to establish a dose-effect relationship and a time-effect relationship for the individual antioxidants on DSBs in human blood lymphocytes. Blood samples from volunteers were irradiated with 10 mGy before and after pre-incubation with different antioxidants (zinc, trolox, lipoic acid, ß-carotene, selenium, vitamin E, vitamin C, N-acetyl-L-cysteine (NAC) and Q 10). Thereby, different pre-incubation times, concentrations and combinations of drugs were evaluated. For assessment of DSBs, lymphocytes were stained against the phosphorylated histone variant γ-H2AX. For zinc, trolox and lipoic acid regardless of concentration or pre-incubation time, no significant decrease of γ-H2AX-foci was found. However, ß-carotene (15%), selenium (14%), vitamin E (12%), vitamin C (25%), NAC (43%) and Q 10 (18%) led to a significant reduction of γ-H2AX-foci at a pre-incubation time of 1 hour. The combination of different antioxidants did not have an additive effect. Antioxidants administered prior to irradiation demonstrated the potential to reduce γ-H2AX-foci in blood lymphocytes.

  15. Interaction between dental metals and antioxidants, assessed by cytotoxicity assay and ESR spectroscopy.

    Science.gov (United States)

    Kinoshita, Naoto; Yamamura, Takahiko; Teranuma, Hiroshi; Katayama, Tadashi; Tamanyu, Mikako; Negoro, Takaharu; Satoh, Kazue; Sakagami, Hiroshi

    2002-01-01

    Among dental metals, copper showed the highest cytotoxicity against human oral squamous cell carcinoma and human submandibular gland carcinoma cells, followed by palladium-alloy, gold and silver. Normal human cells (gingival fibroblast, pulp cells, periodontal ligament fibroblast) were relatively resistant to these metals. The palladium-alloy failed to induce internucleosomal DNA fragmentation, a biochemical hallmark of apoptosis, in human promyelocytic leukemic HL-60 cells. The cytotoxic activity of the palladium-alloy was significantly reduced by a non-cytotoxic concentration of N-acetyl-L-cysteine, or more efficiently by sodium ascorbate. However, higher concentrations of sodium ascorbate enhanced the cytotoxic activity of palladium-alloy. ESR spectroscopy showed that the palladium-alloy enhanced the intensity of ascorbate radical, suggesting the possible interaction between metals and antioxidants. All metals, except copper, did not significantly affect the generation of superoxide anion (by hypoxanthine-xanthine oxidase reaction), hydroxyl radical (by Fenton reaction) and nitric oxide (from NOC-7 in the presence of C-PTIO). These data demonstrate for the first time that antioxidants modify the biological activity of dental metals.

  16. Chemical decontamination with n-acetyl-l-cysteine-sodium hydroxide improves recovery of viable Mycobacterium avium subsp. paratuberculosis organisms from cultured milk

    Science.gov (United States)

    Mycobacterium avium subsp. paratuberculosis (MAP) is shed into milk and feces of cows with advanced Johne’s disease, allowing transmission of MAP among animals. The objective of this study was to formulate an optimized protocol for the isolation of MAP from milk. Parameters investigated included che...

  17. L-cysteine, N-acetyl-L-cysteine, and glutathione protect xenopus laevis embryos against acrylamide-induced malformations and mortality in the frog embryo teratogenesis assay (FETAX)

    Science.gov (United States)

    Dietary acrylamide is largely derived from heat-induced reactions between the amino group of the free amino acid asparagine and carbonyl groups of glucose and fructose during heat processing (baking, frying) of plant-derived foods such as potato fries and cereals. After consumption, acrylamide is a...

  18. Do antioxidant vitamins ameliorate the beneficial effects of exercise training on insulin sensitivity?

    Science.gov (United States)

    Lavie, Carl J; Milani, Jenna N

    2011-01-01

    Exercise training has numerous health benefits, and in patients with type 2 diabetes mellitus and metabolic syndrome, it can improve insulin sensitivity and glucose control. A recent publication suggests that antioxidant vitamins (C and E) block these effects on blood glucose. This investigation was undertaken to determine whether antioxidant vitamins ameliorate the beneficial effects of cardiac rehabilitation and exercise training (CRET) on insulin sensitivity and glucose metabolism in patients with coronary heart disease (CHD). We assessed CHD risk factors, including clinical indices of glucose metabolism, and evaluated the effects of exercise training in 315 patients with CHD with diabetes mellitus and/or metabolic syndrome before and after a 3-month program of CRET. Patients were divided into 2 groups based on self-reported antioxidant vitamin (vitamins C and E) consumption. Both groups, 113 patients (36%) consuming vitamins (Vits group) and 202 patients (64%) who reported no vitamin use (no-Vits group) were statistically similar at baseline. Following CRET, patients improved exercise capacity (10%, P vitamin E and 500 mg of vitamin C) do not ameliorate the health benefits of exercise training, including fasting blood glucose, in CHD patients

  19. Role of hydrotherapy in the amelioration of oxidant-antioxidant status in rheumatoid arthritis patients.

    Science.gov (United States)

    Mateen, Somaiya; Moin, Shagufta; Khan, Abdul Q; Zafar, Atif; Fatima, Naureen; Shahzad, Sumayya

    2017-06-14

    Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. Reactive oxygen species (ROS) are involved in the pathophysiology of RA. Moderate intensity exercises have been reported to have anti-oxidant and anti-inflammatory effects. The aim of this study was to evaluate the effect of hydrotherapy on oxidant-antioxidant status in RA patients. Forty RA patients and 30 age- and sex-matched healthy controls were included in this study. RA patients were subdivided into two groups: the first group (n = 20) received treatment with conventional RA drugs, while the second group (n = 20) received hydrotherapy along with the conventional drugs for a period of 12 weeks. Disease Activity Score of 28 joints (DAS-28), ROS level, protein oxidation, lipid peroxidation, DNA damage and the activities of antioxidant enzymes were evaluated before and after 12 weeks of treatment. RA patients showed a significant change in the oxidative stress biomarkers (ROS, P hydrotherapy has decreased protein, lipid and DNA oxidation by increasing the activities of antioxidant enzymes (SOD and GPx). Our results indicate that hydrotherapy along with drugs has reduced the severity of disease (DAS-28) by ameliorating the oxidant-antioxidant status in RA patients. Thus, in addition to conventional drugs, RA patients should be advised to have hydrotherapy (moderate intensity exercise) in their treatment regimen. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  20. Treatment with antioxidants ameliorates oxidative damage in a mouse model of propionic acidemia.

    Science.gov (United States)

    Rivera-Barahona, Ana; Alonso-Barroso, Esmeralda; Pérez, Belén; Murphy, Michael P; Richard, Eva; Desviat, Lourdes R

    2017-09-01

    Oxidative stress contributes to the pathogenesis of propionic acidemia (PA), a life threatening disease caused by the deficiency of propionyl CoA-carboxylase, in the catabolic pathway of branched-chain amino acids, odd-number chain fatty acids and cholesterol. Patients develop multisystemic complications including seizures, extrapyramidal symptoms, basal ganglia deterioration, pancreatitis and cardiomyopathy. The accumulation of toxic metabolites results in mitochondrial dysfunction, increased reactive oxygen species and oxidative damage, all of which have been documented in patients' samples and in a hypomorphic mouse model. Here we set out to investigate whether treatment with a mitochondria-targeted antioxidant, MitoQ, or with the natural polyphenol resveratrol, which is reported to have antioxidant and mitochondrial activation properties, could ameliorate the altered redox status and its functional consequences in the PA mouse model. The results show that oral treatment with MitoQ or resveratrol decreases lipid peroxidation and the expression levels of DNA repair enzyme OGG1 in PA mouse liver, as well as inducing tissue-specific changes in the expression of antioxidant enzymes. Notably, treatment decreased the cardiac hypertrophy marker BNP that is found upregulated in the PA mouse heart. Overall, the results provide in vivo evidence to justify more in depth investigations of antioxidants as adjuvant therapy in PA. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Lifespan Extension and Sustained Expression of Stem Cell Phenotype of Human Breast Epithelial Stem Cells in a Medium with Antioxidants

    Directory of Open Access Journals (Sweden)

    Kai-Hung Wang

    2016-01-01

    Full Text Available We have previously reported the isolation and culture of a human breast epithelial cell type with stem cell characteristics (Type I HBEC from reduction mammoplasty using the MSU-1 medium. Subsequently, we have developed several different normal human adult stem cell types from different tissues using the K-NAC medium. In this study, we determined whether this low calcium K-NAC medium with antioxidants (N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate is a better medium to grow human breast epithelial cells. The results clearly show that the K-NAC medium is a superior medium for prolonged growth (cumulative population doubling levels ranged from 30 to 40 of normal breast epithelial cells that expressed stem cell phenotypes. The characteristics of these mammary stem cells include deficiency in gap junctional intercellular communication, expression of Oct-4, and the ability to differentiate into basal epithelial cells and to form organoid showing mammary ductal and terminal end bud-like structures. Thus, this new method of growing Type I HBECs will be very useful in future studies of mammary development, breast carcinogenesis, chemoprevention, and cancer therapy.

  2. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nagib, Marwa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Tadros, Mariane G., E-mail: mirogeogo@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); ELSayed, Moushira I. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Khalifa, Amani E. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2013-08-15

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5 days. OLM-M (1, 3 and 10 mg/kg) was administered orally during 21 days prior to the induction of colitis, and for 5 days after. Sulfasalazine (500 mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. - Highlights: • Olmesartan medoximil reduced dextran sodium sulphate- induced colitis. • Mechanism involved anti-inflammatory and antioxidant effects dose- dependently. • It suppressed malondialdehyde and restored reduced glutathione levels. • It reduced inflammatory markers levels and histological changes.

  3. Effects of Ionizing Radiation and Glutathione Precursor on Antioxidant Enzyme and Cell Survival in Yeast

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinkyu; Roh, Changhyun; Ryu, Taeho; Park, Jiyoung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Nili, Michael A. [Oxiage Cosmeceutical Research Institute, Virginia (United States)

    2013-05-15

    Cells react to such an induced oxidative stress through scavenging the generated reactive oxygen species to reduce oxidative damage. Antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase are immediately triggered for reactive oxygen species. N-acetyl-L-cysteine (NAC), a precursor of glutathione, is one of the antioxidants. The effect of NAC as an antioxidant and/or a cell rescue agent was investigated in the present study. Glutathione (GSH) is the most abundant intracellular thiol, which involves in antioxidant defense via direct interaction with ROS or via activities of detoxication enzymes like glutathione peroxidases (GPx). NAC flowed in the cell is converted to cysteine by deacetylation, that is supplied to the depleted GSH by oxidative stress. NAC prevents the depletion of GSH by radiation, increases the production of GSH, and improves enzymes activity such as GPx and alkaline phosphatase. Cell growth and survivorship and transcriptional level of glutathione gene are analyzed in two yeast strains exposed to combined treatment of NAC with gamma-rays. The effect of NAC on cell growth was measured during 72 hours. The cell growth was hampered by higher concentrations of NAC at stationary phase. NAC, however, didn't affect the cell division at the exponential phase. The survival of the cells decreased with radiation dose. The cell viability of the strain W303-1A was reduced significantly at the low dose (10 and 30 Gy). By comparison, the strain W303-1A was more sensitive to radiation with having a half lethal dose (LD{sub 50}) of about 20 Gy. The quantitative RT-PCR analysis showed that the transcriptional expression of antioxidant enzyme gene GPX1 increased after irradiation while the expression of the gene decreased by the combined treatment of NAC with 100 Gy radiation. The present study shows that NAC can directly scavenge ROS against oxidative stress in vivo. In conclusion, NAC can prevent radiation-induced oxidative

  4. Effects of Ionizing Radiation and Glutathione Precursor on Antioxidant Enzyme and Cell Survival in Yeast

    International Nuclear Information System (INIS)

    Kim, Jinkyu; Roh, Changhyun; Ryu, Taeho; Park, Jiyoung; Nili, Michael A.

    2013-01-01

    Cells react to such an induced oxidative stress through scavenging the generated reactive oxygen species to reduce oxidative damage. Antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase are immediately triggered for reactive oxygen species. N-acetyl-L-cysteine (NAC), a precursor of glutathione, is one of the antioxidants. The effect of NAC as an antioxidant and/or a cell rescue agent was investigated in the present study. Glutathione (GSH) is the most abundant intracellular thiol, which involves in antioxidant defense via direct interaction with ROS or via activities of detoxication enzymes like glutathione peroxidases (GPx). NAC flowed in the cell is converted to cysteine by deacetylation, that is supplied to the depleted GSH by oxidative stress. NAC prevents the depletion of GSH by radiation, increases the production of GSH, and improves enzymes activity such as GPx and alkaline phosphatase. Cell growth and survivorship and transcriptional level of glutathione gene are analyzed in two yeast strains exposed to combined treatment of NAC with gamma-rays. The effect of NAC on cell growth was measured during 72 hours. The cell growth was hampered by higher concentrations of NAC at stationary phase. NAC, however, didn't affect the cell division at the exponential phase. The survival of the cells decreased with radiation dose. The cell viability of the strain W303-1A was reduced significantly at the low dose (10 and 30 Gy). By comparison, the strain W303-1A was more sensitive to radiation with having a half lethal dose (LD 50 ) of about 20 Gy. The quantitative RT-PCR analysis showed that the transcriptional expression of antioxidant enzyme gene GPX1 increased after irradiation while the expression of the gene decreased by the combined treatment of NAC with 100 Gy radiation. The present study shows that NAC can directly scavenge ROS against oxidative stress in vivo. In conclusion, NAC can prevent radiation-induced oxidative stress by

  5. Natural Antioxidant-Isoliquiritigenin Ameliorates Contractile Dysfunction of Hypoxic Cardiomyocytes via AMPK Signaling Pathway

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    Xiaoyu Zhang

    2013-01-01

    Full Text Available Isoliquiritigenin (ISL, a simple chalcone-type flavonoid, is derived from licorice compounds and is mainly present in foods, beverages, and tobacco. Reactive oxygen species (ROS is a critical factor involved in modulating cardiac stress response signaling during ischemia and reperfusion. We hypothesize that ISL as a natural antioxidant may protect heart against ischemic injury via modulating cellular redox status and regulating cardioprotective signaling pathways. The fluorescent probe H2DCFDA was used to measure the level of intracellular ROS. The glucose uptake was determined by 2-deoxy-D-glucose-3H accumulation. The IonOptix System measured the contractile function of isolated cardiomyocytes. The results demonstrated that ISL treatment markedly ameliorated cardiomyocytes contractile dysfunction caused by hypoxia. ISL significantly stimulated cardioprotective signaling, AMP-activated protein kinase (AMPK, and extracellular signal-regulated kinase (ERK signaling pathways. The ROS fluorescent probe H2DCFDA determination indicated that ISL significantly reduced cardiac ROS level during hypoxia/reoxygenation. Moreover, ISL reduced the mitochondrial potential (Δψ of isolated mouse cardiomyocytes. Taken together, ISL as a natural antioxidant demonstrated the cardioprotection against ischemic injury that may attribute to the activation of AMPK and ERK signaling pathways and balance of cellular redox status.

  6. Uric acid ameliorates indomethacin-induced enteropathy in mice through its antioxidant activity.

    Science.gov (United States)

    Yasutake, Yuichi; Tomita, Kengo; Higashiyama, Masaaki; Furuhashi, Hirotaka; Shirakabe, Kazuhiko; Takajo, Takeshi; Maruta, Koji; Sato, Hirokazu; Narimatsu, Kazuyuki; Yoshikawa, Kenichi; Okada, Yoshikiyo; Kurihara, Chie; Watanabe, Chikako; Komoto, Shunsuke; Nagao, Shigeaki; Matsuo, Hirotaka; Miura, Soichiro; Hokari, Ryota

    2017-11-01

    Uric acid is excreted from blood into the intestinal lumen, yet the roles of uric acid in intestinal diseases remain to be elucidated. The study aimed to determine whether uric acid could reduce end points associated with nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. A mouse model of NSAID-induced enteropathy was generated by administering indomethacin intraperitoneally to 8-week-old male C57BL/6 mice, and then vehicle or uric acid was administered orally. A group of mice treated with indomethacin was also concurrently administered inosinic acid, a uric acid precursor, and potassium oxonate, an inhibitor of uric acid metabolism, intraperitoneally. For in vitro analysis, Caco-2 cells treated with indomethacin were incubated in the presence or absence of uric acid. Oral administration of uric acid ameliorated NSAID-induced enteropathy in mice even though serum uric acid levels did not increase. Intraperitoneal administration of inosinic acid and potassium oxonate significantly elevated serum uric acid levels and ameliorated NSAID-induced enteropathy in mice. Both oral uric acid treatment and intraperitoneal treatment with inosinic acid and potassium oxonate significantly decreased lipid peroxidation in the ileum of mice with NSAID-induced enteropathy. Treatment with uric acid protected Caco-2 cells from indomethacin-induced oxidative stress, lipid peroxidation, and cytotoxicity. Uric acid within the intestinal lumen and in serum had a protective effect against NSAID-induced enteropathy in mice, through its antioxidant activity. Uric acid could be a promising therapeutic target for NSAID-induced enteropathy. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  7. Antioxidants cause rapid expansion of human adipose-derived mesenchymal stem cells via CDK and CDK inhibitor regulation

    Science.gov (United States)

    2013-01-01

    Background Antioxidants have been shown to enhance the proliferation of adipose-derived mesenchymal stem cells (ADMSCs) in vitro, although the detailed mechanism(s) and potential side effects are not fully understood. In this study, human ADMSCs cultured in ImF-A medium supplemented with antioxidants (N-acetyl-l-cysteine and ascorbic acid-2-phosphate) and fibroblast growth factor 2 (FGF-2) were compared with ADMSCs cultured with FGF-2 alone (ImF) or with FGF-2 under 5% pO2 conditions (ImF-H). Results During log-phase growth, exposure to ImF-A resulted in a higher percentage of ADMSCs in the S phase of the cell cycle and a smaller percentage in G0/G1 phase. This resulted in a significantly reduced cell-doubling time and increased number of cells in the antioxidant-supplemented cultures compared with those supplemented with FGF-2 alone, an approximately 225% higher cell density after 7 days. Western blotting showed that the levels of the CDK inhibitors p21 and p27 decreased after ImF-A treatment, whereas CDK2, CDK4, and CDC2 levels clearly increased. In addition, ImF-A resulted in significant reduction in the expression of CD29, CD90, and CD105, whereas relative telomere length, osteogenesis, adipogenesis, and chondrogenesis were enhanced. The results were similar for ADMSCs treated with antioxidants and those under hypoxic conditions. Conclusion Antioxidant treatment promotes entry of ADMSCs into the S phase by suppressing cyclin-dependent kinase inhibitors and results in rapid cell proliferation similar to that observed under hypoxic conditions. PMID:23915242

  8. Amelioration of radiation stress by antioxidants and prooxidants: role of redox transcription factors

    International Nuclear Information System (INIS)

    Sandur, Santosh Kumar

    2011-01-01

    The development of radiation countermeasures has emerged as a major area of research in radiation biology as ionizing radiation is finding wide applications in power generation, agriculture, food processing, disease diagnosis and therapy. Chemical agents used to alter tissue toxicity of radiation can be broadly divided into three categories based on the time of intervention in relation to radiation. These are: radioprotectors, mitigators, and therapeutic agents. Radiation causes injury to normal tissue by a dynamic process involving generation of reactive oxygen species (ROS), their interactions with bio-molecules, intracellular signaling, cell-to-cell communication, inflammatory responses, tissue repair and cell death. Most of the radiation-induced damage to bio-molecules is caused by the formation of free radicals resulting from the radiolysis of water. However, antioxidants that neutralize free radicals failed to reach clinic. At present, no agent, approved by the U.S. Food and Drug Administration, is available for the treatment of acute radiation syndrome (ARS), although amifostine is approved for prophylaxis of dry mouth (xerostomia) from radiotherapy of head and neck cancers. Therefore, researchers are employing new approaches to ameliorate radiation induced injury. Some of these include use of cytokines, NF-κB (Nuclear factor κB) activators, agents that induce G1 arrest, antibiotics and inhibitors of P53. We have used pro-oxidants to upregulate cytoprotective pathways as a novel strategy to protect against radiation induced hematopoietic syndrome. Different prooxidants including hydrogen peroxide, diethylmaleate, t-butylhydroperoxide and naphthoquinone and its derivatives protected lymphocytes against radiation induced cell death. Further studies were carried out with 1,4-naphthoquinone (NQ) to explore the molecular mechanism of the observed protection. Thiol containing antioxidants abrogated NQ mediated radioprotection in lymphocytes. Addition of NQ to

  9. Role of Some Antioxidants in Ameliorating Disturbances Caused by Gamma Radiation in Female Rats

    International Nuclear Information System (INIS)

    El-Sherbiny, E. M.; Bayomi, M. M.; Addel-Aziz, S. M.

    2007-01-01

    The aim of this research is to investigate the role of supplemental antioxidant vitamins against some sex hormone and trace element disturbances in female rats 1 hour post exposure to 7.0 Gy of gamma radiation as a single dose using 60 Co source. Vitamins C and E were orally administered daily for 2 weeks in doses of 100 mg/kg and 25 mg/kg body weight, respectively. Total number of 48 female albino rats were equally divided into 4 groups; irradiated group (n = 12), vitamin C administered group (n = 12), vitamin E administered group (n = 12) and rats administered vitamin C followed immediately by vitamin E (n =12) post irradiation, in addition to the normal control group (n = 10). The results of this study revealed a significant reduction in serum estradiol level and highly significant reductions in serum progesterone level, zinc and selenium concentrations of female rats exposed to gamma rays, compared to control. Concerning groups administered vitamins, rats administered vitamin C showed a significant improvement in estradiol and progesterone levels, reaching the levels of control group and a non-significant improvement in serum zinc and selenium concentrations was recorded. Vitamin E administered group revealed a high significant increase in serum estradiol level accompanied with an improvement in progesterone, whereas a significant decrease in zinc was found and a significant amelioration in selenium concentration was recorded in comparison with control values. Administration of vitamin E followed immediately by vitamin C resulted in a significant increase in estradiol level and a remarkable improvement in the level of progesterone. Slight significant reduction in zinc was noticed, whereas selenium concentrations were reached normal levels in both E and C and and E groups in comparison with the other groups

  10. Influence of Different Antioxidants on X-Ray Induced DNA Double-Strand Breaks (DSBs) Using γ-H2AX Immunofluorescence Microscopy in a Preliminary Study

    Science.gov (United States)

    Brand, Michael; Sommer, Matthias; Ellmann, Stephan; Wuest, Wolfgang; May, Matthias S.; Eller, Achim; Vogt, Sabine; Lell, Michael M.; Kuefner, Michael A.; Uder, Michael

    2015-01-01

    Background Radiation exposure occurs in X-ray guided interventional procedures or computed tomography (CT) and γ-H2AX-foci are recognized to represent DNA double-strand breaks (DSBs) as a biomarker for radiation induced damage. Antioxidants may reduce the induction of γ-H2AX-foci by binding free radicals. The aim of this study was to establish a dose-effect relationship and a time-effect relationship for the individual antioxidants on DSBs in human blood lymphocytes. Materials and Methods Blood samples from volunteers were irradiated with 10 mGy before and after pre-incubation with different antioxidants (zinc, trolox, lipoic acid, ß-carotene, selenium, vitamin E, vitamin C, N-acetyl-L-cysteine (NAC) and Q 10). Thereby, different pre-incubation times, concentrations and combinations of drugs were evaluated. For assessment of DSBs, lymphocytes were stained against the phosphorylated histone variant γ-H2AX. Results For zinc, trolox and lipoic acid regardless of concentration or pre-incubation time, no significant decrease of γ-H2AX-foci was found. However, ß-carotene (15%), selenium (14%), vitamin E (12%), vitamin C (25%), NAC (43%) and Q 10 (18%) led to a significant reduction of γ-H2AX-foci at a pre-incubation time of 1 hour. The combination of different antioxidants did not have an additive effect. Conclusion Antioxidants administered prior to irradiation demonstrated the potential to reduce γ-H2AX-foci in blood lymphocytes. PMID:25996998

  11. Influence of Different Antioxidants on X-Ray Induced DNA Double-Strand Breaks (DSBs Using γ-H2AX Immunofluorescence Microscopy in a Preliminary Study.

    Directory of Open Access Journals (Sweden)

    Michael Brand

    Full Text Available Radiation exposure occurs in X-ray guided interventional procedures or computed tomography (CT and γ-H2AX-foci are recognized to represent DNA double-strand breaks (DSBs as a biomarker for radiation induced damage. Antioxidants may reduce the induction of γ-H2AX-foci by binding free radicals. The aim of this study was to establish a dose-effect relationship and a time-effect relationship for the individual antioxidants on DSBs in human blood lymphocytes.Blood samples from volunteers were irradiated with 10 mGy before and after pre-incubation with different antioxidants (zinc, trolox, lipoic acid, ß-carotene, selenium, vitamin E, vitamin C, N-acetyl-L-cysteine (NAC and Q 10. Thereby, different pre-incubation times, concentrations and combinations of drugs were evaluated. For assessment of DSBs, lymphocytes were stained against the phosphorylated histone variant γ-H2AX.For zinc, trolox and lipoic acid regardless of concentration or pre-incubation time, no significant decrease of γ-H2AX-foci was found. However, ß-carotene (15%, selenium (14%, vitamin E (12%, vitamin C (25%, NAC (43% and Q 10 (18% led to a significant reduction of γ-H2AX-foci at a pre-incubation time of 1 hour. The combination of different antioxidants did not have an additive effect.Antioxidants administered prior to irradiation demonstrated the potential to reduce γ-H2AX-foci in blood lymphocytes.

  12. Protective effect of antioxidants on DNA damage in leukocytes from X-linked adrenoleukodystrophy patients.

    Science.gov (United States)

    Marchetti, Desirèe P; Donida, Bruna; da Rosa, Helen T; Manini, Paula R; Moura, Dinara J; Saffi, Jenifer; Deon, Marion; Mescka, Caroline P; Coelho, Daniella M; Jardim, Laura B; Vargas, Carmen R

    2015-06-01

    Toxic metabolites accumulation and oxidative stress have been associated to the pathophysiology of X-linked adrenoleukodystrophy (X-ALD), an inborn error of peroxisome metabolism. Parameters of oxidative damage to proteins and lipids in X-ALD patients were already described in literature; however, DNA injuries were not studied yet. Considering that, the aims were to investigate DNA damage by comet assay in heterozygotes and symptomatic X-ALD patients, to look for associations between DNA damage and lipid peroxidation as measured by urinary 15-F2t-isoprostane; and to evaluate the in vitro effect of N-acetyl-l-cysteine (NAC), trolox (TRO) and rosuvastatin (RSV) on DNA damage in leukocytes from symptomatic patients. Symptomatic patients presented higher DNA damage levels than those found in heterozygotes and controls; heterozygotes and controls showed similar results. In order to investigate the in vitro antioxidant effect on DNA damage, whole blood cells from symptomatic patients were incubated with NAC (1 and 2.5mM), TRO (25 and 75 μM) and RSV (0.5, 2 and 5 μM) before DNA damage analysis. NAC, TRO and RSV, at all tested concentrations, were all capable to reduce DNA damage in symptomatic X-ALD patients until control levels. Finally, DNA damage correlated with urinary isoprostanes and plasmatic levels of TBA-RS and DCFH-DA, allowing to hypothesize that DNA damage might be induced by lipid peroxidation in symptomatic patients. The present work yields experimental evidence that NAC, TRO and RSV reduce the in vitro DNA injury in symptomatic X-ALD patients, what may suggest that the administration of these antioxidants might be considered as an adjuvant therapy for X-ALD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Tocotrienol-Rich Fraction Ameliorates Antioxidant Defense Mechanisms and Improves Replicative Senescence-Associated Oxidative Stress in Human Myoblasts

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    Shy Cian Khor

    2017-01-01

    Full Text Available During aging, oxidative stress affects the normal function of satellite cells, with consequent regeneration defects that lead to sarcopenia. This study aimed to evaluate tocotrienol-rich fraction (TRF modulation in reestablishing the oxidative status of myoblasts during replicative senescence and to compare the effects of TRF with other antioxidants (α-tocopherol (ATF and N-acetyl-cysteine (NAC. Primary human myoblasts were cultured to young, presenescent, and senescent phases. The cells were treated with antioxidants for 24 h, followed by the assessment of free radical generation, lipid peroxidation, antioxidant enzyme mRNA expression and activities, and the ratio of reduced to oxidized glutathione. Our data showed that replicative senescence increased reactive oxygen species (ROS generation and lipid peroxidation in myoblasts. Treatment with TRF significantly diminished ROS production and decreased lipid peroxidation in senescent myoblasts. Moreover, the gene expression of superoxide dismutase (SOD2, catalase (CAT, and glutathione peroxidase (GPX1 was modulated by TRF treatment, with increased activity of superoxide dismutase and catalase and reduced glutathione peroxidase in senescent myoblasts. In comparison to ATF and NAC, TRF was more efficient in heightening the antioxidant capacity and reducing free radical insults. These results suggested that TRF is able to ameliorate antioxidant defense mechanisms and improves replicative senescence-associated oxidative stress in myoblasts.

  14. Tocotrienol-Rich Fraction Ameliorates Antioxidant Defense Mechanisms and Improves Replicative Senescence-Associated Oxidative Stress in Human Myoblasts.

    Science.gov (United States)

    Khor, Shy Cian; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum; Abdul Karim, Norwahidah; Makpol, Suzana

    2017-01-01

    During aging, oxidative stress affects the normal function of satellite cells, with consequent regeneration defects that lead to sarcopenia. This study aimed to evaluate tocotrienol-rich fraction (TRF) modulation in reestablishing the oxidative status of myoblasts during replicative senescence and to compare the effects of TRF with other antioxidants ( α -tocopherol (ATF) and N -acetyl-cysteine (NAC)). Primary human myoblasts were cultured to young, presenescent, and senescent phases. The cells were treated with antioxidants for 24 h, followed by the assessment of free radical generation, lipid peroxidation, antioxidant enzyme mRNA expression and activities, and the ratio of reduced to oxidized glutathione. Our data showed that replicative senescence increased reactive oxygen species (ROS) generation and lipid peroxidation in myoblasts. Treatment with TRF significantly diminished ROS production and decreased lipid peroxidation in senescent myoblasts. Moreover, the gene expression of superoxide dismutase (SOD2) , catalase (CAT), and glutathione peroxidase (GPX1) was modulated by TRF treatment, with increased activity of superoxide dismutase and catalase and reduced glutathione peroxidase in senescent myoblasts. In comparison to ATF and NAC, TRF was more efficient in heightening the antioxidant capacity and reducing free radical insults. These results suggested that TRF is able to ameliorate antioxidant defense mechanisms and improves replicative senescence-associated oxidative stress in myoblasts.

  15. Thiol antioxidant-functionalized CdSe/ZnS quantum dots: synthesis, characterization, cytotoxicity.

    Science.gov (United States)

    Zheng, Hong; Mortensen, Luke J; DeLouise, Lisa A

    2013-03-01

    Nanotechnology is a growing industry with wide ranging applications in consumer product and technology development. In the biomedical field, nanoparticles are finding increasing use as imaging agents for biomolecular labeling and tumor targeting. The nanoparticle physiochemical properties must be tailored for the specific application. For example, nanoparticle chemical and physical stability in the biological milieu (no oxidation, aggregation, agglomeration or toxicity) are often required. Nanoparticles used for biomolecular fluorescent imaging should also have high quantum yield (QY). The aim of this paper is to examine the QY, stability, and cell toxicity of a series of positive, negative and neutral surface charge quantum dot (QD) nanoparticles. Simple protocols are described to prepare water soluble QDs by modifying the surface with thiol containing antioxidant ligands and polymers keeping the QD core/shell composition constant. The ligands used to produce negatively charged QDs include glutathione (GSH), N-acetyl-L-cysteine (NAC), dihydrolipoic acid (DHLA), tiopronin (TP), bucilliamine (BUC), and mercaptosuccinic acid (MSA). Ligands used to produce positively charged QDs include cysteamine (CYS) and polyethylenimine (PEI). Dithiothreitol (DTT) was used to produce neutral charged QDs. Commercially available nonaqueous octadecylamine (ODA) capped QDs served as the starting material. Our results suggest that QD uptake and cytotoxicity are both dependent on surface ligand coating composition. The negative charged GSH coated QDs show superior performance exhibiting low cytotoxicity, high stability, high QY and therefore are best suited for bioimaging applications. PEI coated QD also show superior performance exhibiting high QY and stability. However, they are considerably more cytotoxic due to their high positive charge which is an advantageous property that can be exploited for gene transfection and/or tumor targeting applications. The synthetic procedures

  16. Garlic Supplementation Ameliorates UV-Induced Photoaging in Hairless Mice by Regulating Antioxidative Activity and MMPs Expression

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    Hye Kyung Kim

    2016-01-01

    Full Text Available UV exposure is associated with oxidative stress and is the primary factor in skin photoaging. UV-induced reactive oxygen species (ROS cause the up-regulation of metalloproteinase (MMPs and the degradation of dermal collagen and elastic fibers. Garlic and its components have been reported to exert antioxidative effects. The present study investigated the protective effect of garlic on UV-induced photoaging and MMPs regulation in hairless mice. Garlic was supplemented in the diet, and Skh-1 hairless mice were exposed to UV irradiation five days/week for eight weeks. Mice were divided into four groups; Non-UV, UV-irradiated control, UV+1% garlic powder diet group, and UV+2% garlic powder diet group. Chronic UV irradiation induced rough wrinkling of the skin with hyperkeratosis, and administration of garlic diminished the coarse wrinkle formation. UV-induced dorsal skin and epidermal thickness were also ameliorated by garlic supplementation. ROS generation, skin and serum malondialdehyde levels were significantly increased by UV exposure and were ameliorated by garlic administration although the effects were not dose-dependent. Antioxidant enzymes such as superoxide dismutase and catalase activities in skin tissues were markedly reduced by UV irradiation and garlic treatment increased these enzyme activities. UV-induced MMP-1 and MMP-2 protein levels were suppressed by garlic administration. Furthermore, garlic supplementation prevented the UV-induced increase of MMP-1 mRNA expression and the UV-induced decrease of procollagen mRNA expression. These results suggest that garlic may be effective for preventing skin photoaging accelerated by UV irradiation through the antioxidative system and MMP regulation.

  17. Garlic Supplementation Ameliorates UV-Induced Photoaging in Hairless Mice by Regulating Antioxidative Activity and MMPs Expression.

    Science.gov (United States)

    Kim, Hye Kyung

    2016-01-08

    UV exposure is associated with oxidative stress and is the primary factor in skin photoaging. UV-induced reactive oxygen species (ROS) cause the up-regulation of metalloproteinase (MMPs) and the degradation of dermal collagen and elastic fibers. Garlic and its components have been reported to exert antioxidative effects. The present study investigated the protective effect of garlic on UV-induced photoaging and MMPs regulation in hairless mice. Garlic was supplemented in the diet, and Skh-1 hairless mice were exposed to UV irradiation five days/week for eight weeks. Mice were divided into four groups; Non-UV, UV-irradiated control, UV+1% garlic powder diet group, and UV+2% garlic powder diet group. Chronic UV irradiation induced rough wrinkling of the skin with hyperkeratosis, and administration of garlic diminished the coarse wrinkle formation. UV-induced dorsal skin and epidermal thickness were also ameliorated by garlic supplementation. ROS generation, skin and serum malondialdehyde levels were significantly increased by UV exposure and were ameliorated by garlic administration although the effects were not dose-dependent. Antioxidant enzymes such as superoxide dismutase and catalase activities in skin tissues were markedly reduced by UV irradiation and garlic treatment increased these enzyme activities. UV-induced MMP-1 and MMP-2 protein levels were suppressed by garlic administration. Furthermore, garlic supplementation prevented the UV-induced increase of MMP-1 mRNA expression and the UV-induced decrease of procollagen mRNA expression. These results suggest that garlic may be effective for preventing skin photoaging accelerated by UV irradiation through the antioxidative system and MMP regulation.

  18. Curcumin-induced fibroblast apoptosis and in vitro wound contraction are regulated by antioxidants and heme oxygenase: implications for scar formation

    Science.gov (United States)

    Scharstuhl, A; Mutsaers, HAM; Pennings, SWC; Szarek, WA; Russel, FGM; Wagener, FADTG

    2009-01-01

    Abstract Fibroblast apoptosis plays a crucial role in normal and pathological scar formation and therefore we studied whether the putative apoptosis-inducing factor curcumin affects fibroblast apoptosis and may function as a novel therapeutic. We show that 25-μM curcumin causes fibroblast apoptosis and that this could be inhibited by co-administration of antioxidants N-acetyl-l-cysteine (NAC), biliverdin or bilirubin, suggesting that reactive oxygen species (ROS) are involved. This is supported by our observation that 25-μM curcumin caused the generation of ROS, which could be completely blocked by addition of NAC or bilirubin. Since biliverdin and bilirubin are downstream products of heme degradation by heme oxygenase (HO), it has been suggested that HO-activity protects against curcumin-induced apoptosis. Interestingly, exposure to curcumin maximally induced HO-1 protein and HO-activity at 10–15 μM, whereas, at a concentration of >20-μM curcumin HO-1-expression and HO-activity was negligible. NAC-mediated inhibition of 25-μM curcumin-induced apoptosis was demonstrated to act in part via restored HO-1-induction, since the rescuing effect of NAC could be reduced by inhibiting HO-activity. Moreover pre-induction of HO-1 using 5-μM curcumin protected fibroblasts against 25-μM curcumin-induced apoptosis. On a functional level, fibroblast-mediated collagen gel contraction, an in vitro wound contraction model, was completely prevented by 25-μM curcumin, while this could be reversed by co-incubation with NAC, an effect that was also partially HO-mediated. In conclusion, curcumin treatment in high doses (>25 μM) may provide a novel way to modulate pathological scar formation through the induction of fibroblast apoptosis, while antioxidants, HO-activity and its effector molecules act as a possible fine-tuning regulator. PMID:18410527

  19. The effect of antioxidants on oxidative DNA damage induced by visible-light-irradiated camphorquinone/N,N-dimethyl-p-toluidine.

    Science.gov (United States)

    Winter, Kyle; Pagoria, Dustin; Geurtsen, Werner

    2005-09-01

    Previous investigations have found that visible-light (VL)-irradiated camphorquinone (CQ), in the presence of a tertiary amine (e.g., N,N-dimethyl-p-toluidine, DMT), generates reactive oxygen species and causes oxidative DNA damage in vitro. In this study, oxidative DNA damage produced by VL-irradiated CQ/DMT, in the presence and absence of antioxidants (glutathione, N-acetyl-L-cysteine (NAC), mannitol, vitamin C, and vitamin E), was measured by the conversion of PhiX-174 RF I supercoiled (SC) double-stranded plasmid DNA into open and linear forms. VL-irradiated CQ/DMT, lacking antioxidant, damaged 99.4 +/- 1% of the PhiX-174 RF I SC double-stranded plasmid DNA. Our results revealed that glutathione (10.0, 5.0, 2.5, 1.0, and 0.5 mm) and NAC (10.0, 5.0, and 2.5 mm) significantly (p < 0.02) reduced oxidative DNA damage produced by VL-irradiated CQ/DMT. Vitamin E, vitamin C, and mannitol were ineffective at reducing oxidative DNA damage produced by VL-irradiated CQ/DMT. Furthermore, vitamin E (10.0 and 5.0 mm) and vitamin C (10.0, 5.0, 2.5, 1.0, 0.5 mm) treatment significantly (p < 0.02) enhanced VL-irradiated CQ/DMT-induced oxidative DNA damage and caused significant (p < 0.001) DNA damage following VL-irradiation in the absence of CQ/DMT. As a result, future studies should evaluate whether glutathione and NAC effectively reduce or prevent oxidative damage induced by VL-irradiated CQ/DMT in vivo.

  20. Protective effects of antioxidants on micronuclei induced by camphorquinone/N,N-dimethyl-p-toluidine employing in vitro mammalian test system.

    Science.gov (United States)

    Li, Yi-Ching; Huang, Fu-Mei; Lee, Shiaun-Shinn; Lin, Ruey-Hseng; Chang, Yu-Chao

    2007-07-01

    Camphorquinone (CQ) is widely used as an initiator in modern visible-light (VL) cured resin systems. CQ is also characterized as a potential allergenic compound. To date, there is growing concern that CQ may produce genetic damage by inducing mutation. In this study, CQ in the presence of reducing agent N,N-dimethyl-p-toluidine (DMT) with or without VL irradiation was analyzed for the induction of chromosomal aberrations indicated by micronuclei (MN) induced in CHO cells. Our data demonstrated that an increase in the numbers of MN was observed with CQ/DMT with or without VL irradiation (p < 0.05). Significant prolongation of cell cycles was observed by the treatment with CQ/DMT with or without VL irradiation (p < 0.05). In addition, VL irradiated CQ/DMT was found to exhibit significantly genotoxic and cytotoxic effects as compared with CQ/DMT alone (p < 0.05). Furthermore, to determine whether oxidative stress could modulate the MN induced by CQ/DMT with or without VL irradiation in CHO cells, cells were pre-treated with various antioxidants 10 mM N-acetyl-L-cysteine (NAC), 2 mM ascorbic acid, and 2 mM alpha-tocopherol. The pre-treatment with antioxidants could antagonize not only the increased MN cells but also the prolonged cell cycle induced by CQ/DMT with or without VL irradiation in CHO cells (p < 0.05). Our findings provide the evidences for the induction of MN by CQ/DMT employing mammalian test system, indicating clastogenic activity of CQ/DMT with or without VL irradiation in vitro. In addition, VL irradiated CQ/DMT exhibits higher genotoxic and cytotoxic effects than CQ/DMT alone. Moreover, NAC, ascorbic acid, and alpha-tocopherol act as the antagonists against the genotoxicity and cytotoxicity of CQ/DMT with or without VL irradiation. Copyright 2006 Wiley Periodicals, Inc.

  1. Role of enzymatic and non enzymatic antioxidant in ameliorating salinity induced damage in nostoc muscorum

    International Nuclear Information System (INIS)

    Hend, A.; Abeer, A.; Allah, A.

    2015-01-01

    Presence of high salt concentration in the growth medium adversely affected the plant growth and productivity by altering its metabolic activities. Experiments were conducted on cyanobacteriaum Nostoc muscorum grown in nitrogen free medium supplemented with 250 mM NaCl to evaluate the salt stress induced changes in growth, antioxidants and lipid composition. Salt stress significantly reduced the growth and physio-biochemical attributes. Salt stress increased malonaldehyde content thereby causing alterations in the lipid fraction. Significant reduction in polyunsaturated fatty acids including phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI) and phosphatidylserine (PS) was observed. Where as diacylglycerol, sterol ester and non-esterified fatty acids were increased. Activities of antioxidant enzymes and contents of non-enzymatic antioxidants including glutathione enhanced due to salt stress. An increase in accumulation of proline was also observed. Hence increased activity of antioxidants and altered fatty acid composition was observed in salt stressed Nostoc muscorum. (author)

  2. The role of thymoquinone as a potent antioxidant in ameliorating the neurotoxic effect of sodium arsenate in female rat

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    Rami B. Kassab

    2017-09-01

    Full Text Available Arsenic is a neurotoxic substance that makes the brain susceptible to free radicals. Thymoquinone (TQ is a potent antioxidant extracted from Nigella sativa seeds. It scavenges free radicals and prevents the cell damage resulted from oxidative substances. In this study, the ameliorative effect of TQ in arsenic-induced neurotoxicity was investigated. Rats were treated for 21 days with: distilled water, 20 mg/kg sodium arsenate, 10 mg/kg TQ, and arsenate followed by TQ. Cerebral cortex, cerebellum and brain stem were removed for the measurements of different physiological parameters. Cerebelli were prepared for histopathological studies. Arsenate treatment caused a decrease in the levels of norepinephrine (NE, dopamine (DA, acetylcholine esterase (AChE and Na+-K+-ATPase activities in cerebral cortex, cerebellum, and brain stem of rats. Similarly, the levels of glutathione (GSH, glutathione peroxidase (GPx, glutathione reductase (GR, superoxide dismutase (SOD, catalase (CAT were declined. In contrast, serotonin (5-HT, lipid peroxidation (MDA, nitrite/nitrate (NO, and tumour necrosis factor (TNF-α levels were increased after arsenate treatment. The presence of degenerated Purkinje cells in cerebellum was noticed. Results revealed that, post-treatment with TQ suppressed the arsenate-induced neurotoxic effects as it decreased the levels of 5-HT, MAD, NO, TNF-α and increased the levels of NE, DA, GH, GPx, GR, SOD, and CAT, in the cerebral cortex, cerebellum, and brain stem. Likewise, AChE and Na+-K+-ATPase activities were increased after TQ post-treatment. In conclusion, TQ ameliorated the neurotoxic effect of arsenate and suppressed the oxidative stress induced in the nervous system through its antioxidant mechanism.

  3. Study of the anti-inflammatory effects of low-dose radiation. The contribution of biphasic regulation of the antioxidative system in endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Large, Martin; Hehlgans, Stephanie; Reichert, Sebastian; Roedel, Claus; Roedel, Franz [Goethe University Frankfurt, Department of Radiotherapy and Oncology, Frankfurt am Main (Germany); Gaipl, Udo S. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Fournier, Claudia [GSI Helmholtz Center for Heavy Ion Research, Department of Biophysics, Darmstadt (Germany); Weiss, Christian [Goethe University Frankfurt, Department of Radiotherapy and Oncology, Frankfurt am Main (Germany); Klinikum Darmstadt, Institute for Radiooncology and Radiotherapy, Darmstadt (Germany)

    2015-09-15

    We examined (a) the expression of the antioxidative factor glutathione peroxidase (GPx) and the transcription factor nuclear factor E2-related factor 2 (Nrf2) following low-dose X-irradiation in endothelial cells (ECs) and (b) the impact of reactive oxygen species (ROS) and Nrf2 on functional properties of ECs to gain further knowledge about the anti-inflammatory mode of action of low doses of ionizing radiation. EA.hy926 ECs and primary human dermal microvascular ECs (HMVEC) were stimulated by tumor necrosis factor-α (TNF-α, 20 ng/ml) 4 h before irradiation with single doses ranging from 0.3 to 3 Gy. The expression and activity of GPx and Nrf2 were analyzed by flow cytometry, colorimetric assays, and real-time PCR. The impact of ROS and Nrf2 on peripheral blood mononuclear cell (PBMC) adhesion was assayed in the presence of the ROS scavenger N-acetyl-L-cysteine (NAC) and Nrf2 activator AI-1. Following a low-dose exposure, we observed in EA.hy926 EC and HMVECs a discontinuous expression and enzymatic activity of GPx concomitant with a lowered expression and DNA binding activity of Nrf2 that was most pronounced at a dose of 0.5 Gy. Scavenging of ROS by NAC and activation of Nrf2 by AI-1 significantly diminished a lowered adhesion of PBMC to EC at a dose of 0.5 Gy. Low-dose irradiation resulted in a nonlinear expression and activity of major compounds of the antioxidative system that might contribute to anti-inflammatory effects in stimulated ECs. (orig.) [German] Ziel der Studie war die Untersuchung der Expression des antioxidativen Enzyms Glutathionperoxidase (GPx) und des Transkriptionsfaktors ''nuclear factor E2-related factor 2'' (Nrf2) in Endothelzellen nach niedrigdosierter Roentgenbestrahlung. Des Weiteren wurde der Einfluss von reaktiven Sauerstoffmetaboliten (ROS) und von Nrf2 auf funktionelle Eigenschaften von Endothelzellen analysiert, um weitere Erkenntnisse ueber die antientzuendliche Wirkung von niedrigdosierten Roentgenstrahlen

  4. Folate Receptor–Targeted Antioxidant Therapy Ameliorates Renal Ischemia–Reperfusion Injury

    Science.gov (United States)

    Knight, Sarah F.; Kundu, Kousik; Joseph, Giji; Dikalov, Sergey; Weiss, Daiana; Murthy, Niren

    2012-01-01

    Antioxidant therapy can protect against ischemic injury, but the inability to selectively target the kidney would require extremely high doses to achieve effective local concentrations of drug. Here, we developed a directed therapeutic that specifically targets an antioxidant to renal proximal tubule cells via the folate receptor. Because a local increase in superoxide contributes to renal ischemic injury, we created the folate-antioxidant conjugate 4-hydroxy-Tempo (tempol)-folate to target folate receptors, which are highly expressed in the proximal tubule. Dihydroethidium high-performance liquid chromatography demonstrated that conjugated tempol retained its efficacy to scavenge superoxide in proximal tubule cells. In a mouse model of renal ischemia-reperfusion injury, tempol-folate reduced renal superoxide levels more effectively than tempol alone. Furthermore, electron spin resonance revealed the successful targeting of the tempol-folate conjugate to the kidney and other tissues expressing folate receptors. Administration of tempol-folate protected the renal function of mice after ischemia-reperfusion injury and inhibited infiltration of macrophages. In conclusion, kidney-specific targeting of an antioxidant has therapeutic potential to prevent renal ischemic injury. Conjugation of other pharmaceuticals to folate may also facilitate the development of treatments for other kidney diseases. PMID:22282594

  5. Amelioration of cholesterol induced atherosclerosis by normalizing gene expression, cholesterol profile and antioxidant enzymes by Vigna unguiculata.

    Science.gov (United States)

    Janeesh, P A; Abraham, Annie

    2013-06-01

    Cardiovascular diseases, especially atherosclerosis, have found to be the dreadful diseases worldwide and therapeutic interventions using plant sources have wide therapeutic value. Vigna unguiculata (VU) leaves have been used as food and therapeutics. Hence, our study was designed to evaluate the hypolipidemic as well as anti-atherogenic potential of VU leaves in normalizing atherogenic gene expression, cholesterol profile, generation of reactive oxygen species (ROS) and antioxidant enzyme system on cholesterol fed rabbit model. For the study New Zealand white rabbits were randomly divided into four groups of six animals each and experimental period was three months; group -i - ND [normal diet (40 g feed)], group-ii- ND (normal diet) +EAVU [ethyl acetate fraction of Vigna unguiculata (150 mg/kg body weight)], group -iii- ND [normal diet ]+ CFD [cholesterol fed diet (cholesterol 1 % of 40 g feed and cholic acid 0.5 % of 40 g feed)] and group-iv - ND [normal diet] +CFD [cholesterol fed diet ]+EAVU [ethyl acetate fraction of Vigna unguiculata (150 mg/kg body weight)]. Atherosclerosis was induced by feeding the rabbit with cholesterol (1 % of 40 g feed) and cholic acid (0.5 % of 40 g feed). Supplementation of EAVU normalized cholesterol profile, generation of reactive oxygen species (ROS), lipid peroxidation products like thiobarbituric acid reactive substance (TBARS), antioxidant system and important genes of cardiovascular diseases like interleukin-10 (IL 10), paraoxanase-1 (PON I), interleukin-6 (IL 6), and cyclooxygenase-2 (Cox 2) to near normal level as compared with normal diet. The result obtained showed the antioxidant as well as anti-atherogenic potential of Vigna unguiculata leaves in ameliorating cholesterol induced atherosclerosis, and thus it is good task to include VU leaves in daily diet for the prevention of cardiovascular diseases especially atherosclerosis.

  6. Antioxidative phytoceuticals to ameliorate pancreatitis in animal models: An answer from nature

    Science.gov (United States)

    Park, Jong-Min; Lee, Sooyeon; Chung, Mi Kyung; Kwon, Sung-Hun; Kim, Eun-Hee; Ko, Kwang Hyun; Kwon, Chang Il; Hahm, Ki Baik

    2014-01-01

    Despite enthusiastic efforts directed at elucidating critical underlying mechanisms towards the identification of novel therapeutic targets for severe acute pancreatitis (SAP), the disease remains without a specific therapy to be executed within the first hours to days after onset of symptoms. Although earlier management for SAP should aim to either treat organ failure or reduce infectious complications, the current standard of care for the general management of AP in the first hours to days after onset of symptoms include intravenous fluid replacement, nutritional changes, and the use of analgesics with a close monitoring of vital signs. Furthermore, repeated evaluation of severity is very important, as the condition is particularly unstable in the early stages. In cases where biliary pancreatitis is accompanied by acute cholangitis or in cases where biliary stasis is suspected, an early endoscopic retrograde cholangiopancreatography is recommended. However, practice guidelines regarding the treatment of pancreatitis are suboptimal. In chronic pancreatitis, conservative management strategies include lifestyle modifications and dietary changes followed by analgesics and pancreatic enzyme supplementation. Recently, attention has been focused on phytoceuticals or antioxidants as agents that could surpass the limitations associated with currently available therapies. Because oxidative stress has been shown to play an important role in the pathogenesis of pancreatitis, antioxidants alone or combined with conventional therapy may improve oxidative-stress-induced organ damage. Interest in phytoceuticals stems from their potential use as simple, accurate tools for pancreatitis prognostication that could replace older and more tedious methods. Therefore, the use of antioxidative nutrition or phytoceuticals may represent a new direction for clinical research in pancreatitis. In this review article, recent advances in the understanding of the pathogenesis of pancreatitis are

  7. Spirulina ameliorates methotrexate hepatotoxicity via antioxidant, immune stimulation, and proinflammatory cytokines and apoptotic proteins modulation.

    Science.gov (United States)

    Khafaga, Asmaa F; El-Sayed, Yasser S

    2018-03-01

    Methotrexate (MTX) is an efficient cytotoxic drug used against various carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity of MTX limits its use. Therefore, the present study aimed to evaluate the potential hepatoprotective and immune-stimulant effect of Spirulina platensis (SP) against MTX acute toxicity. Thirty-two male Wistar rats were randomly allocated into the following four groups (n = 8): control, SP (500 mg/kg bwt, oral gavage daily for 21 days), MTX (20 mg/kg bwt, single ip injection), and MTX+SP. Hepatic and splenic histoarchitecture, leukocyte counts and serum immunoglobulins were evaluated. Hepatic oxidant/antioxidant status, proinflammatory cytokines (tumor necrosis factor-α, and interleukin 6), and pro-apoptotic proteins (caspase 3 and Bax) immunoexpression were assessed. MTX induced extensive hepatic necrosis and vacuolation, and sever lymphoid depletion in splenic white pulp with increased levels of serum transaminases, lactate dehydrogenase, and hepatic malondialdehyde, tumor necrosis factor-α and interleukin 6; and number of caspase 3- and Bax-positive hepatocytes. A significant decrease in leukocyte counts, serum immunoglobulins (IgA, IgM and IgG) level, and hepatic antioxidant enzymes (GSH, GPx, SOD, and CAT) was also detected. Pretreatment with SP resulted in significant improvements in hepatic and splenic histologic architecture, as well as restoring liver enzymes and reduction of lipid peroxidation product, proinflammatory cytokines, and caspase 3 and Bax immunoexpression. Additionally, a significant increase in antioxidant enzymes, serum immunoglobulins, and total leukocyte counts was demonstrated. SP possesses promising antioxidant, anti-inflammatory, anti-apoptotic and immune stimulatory properties against MTX-induced hepatotoxicity and immunosuppression. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects.

    Directory of Open Access Journals (Sweden)

    Keisuke Ishizawa

    Full Text Available Diabetic nephropathy (DN is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice, NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.

  9. Short communication: Application of an N-acetyl-L-cysteine-NaOH decontamination method for the recovery of viable Mycobacterium avium subsp. paratuberculosis from milk of naturally infected cows

    Science.gov (United States)

    Mycobacterium avium subsp. paratuberculosis (MAP) is shed into the milk of cattle affected by Johne’s disease and, therefore, is a route of transmission for infection in youngstock in dairy herds. The objective of this study was to validate a decontamination and culture protocol for the recovery of ...

  10. Oxidative Stress in The Hippocampus During Experimental Seizures Can Be Ameliorated With The Antioxidant Ascorbic Acid

    Directory of Open Access Journals (Sweden)

    Ítala Mônica Sales Santos

    2009-01-01

    Full Text Available Ascorbic acid has many nonenzymatic actions and is a powerful water-soluble antioxidant. It protects low density lipoproteins from oxidation and reduces harmful oxidants in the central nervous system. Pilocarpine-induced seizures have been suggested to be mediated by increases in oxidative stress. Current studies have suggested that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures. The objective of the present study was to evaluate the neuroprotective effects of ascorbic acid (AA in rats, against the observed oxidative stress during seizures induced by pilocarpine. Wistar rats were treated with 0.9% saline (i.p., control group, ascorbic acid (500 mg/kg, i.p., AA group, pilocarpine (400 mg/kg, i.p., pilocarpine group, and the association of ascorbic acid (500 mg/kg, i.p. plus pilocarpine (400 mg/kg, i.p., 30 min before of administration of ascorbic acid (AA plus pilocarpine group. After the treatments all groups were observed for 6 h. The enzyme activities as well as the lipid peroxidation and nitrite concentrations were measured using spectrophotometric methods and the results compared to values obtained from saline and pilocarpine-treated animals. Protective effects of ascorbic acid were also evaluated on the same parameters. In pilocarpine group there was a significant increase in lipid peroxidation and nitrite level. However, no alteration was observed in superoxide dismutase and catalase activities. Antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content as well as increased the superoxide dismutase and catalase activities in hippocampus of adult rats after seizures induced by pilocarpine. Our findings strongly support the hypothesis that oxidative stress in hippocampus occurs during seizures induced by pilocarpine, proving that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, and also imply that a

  11. Sulforaphane Ameliorates Okadaic Acid-Induced Memory Impairment in Rats by Activating the Nrf2/HO-1 Antioxidant Pathway.

    Science.gov (United States)

    Dwivedi, Subhash; Rajasekar, N; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2016-10-01

    Okadaic acid (OKA) causes memory impairment and attenuates nuclear factor erythroid 2-related factor 2 (Nrf2) along with oxidative stress and neuroinflammation in rats. Sulforaphane (dietary isothiocyanate compound), an activator of Nrf2 signaling, exhibits neuroprotective effects. However, the protective effect of sulforaphane in OKA-induced neurotoxicity remains uninvestigated. Therefore, in the present study, the role of sulforaphane in OKA-induced memory impairment in rats was explored. A significant increased Nrf2 expression in the hippocampus and cerebral cortex was observed in trained (Morris water maze) rats, and a significant decreased Nrf2 expression in memory-impaired (OKA, 200 ng icv) rats indicated its involvement in memory function. Sulforaphane administration (5 and 10 mg/kg, ip, days 1 and 2) ameliorates OKA-induced memory impairment in rats. The treatment also restored Nrf2 and its downstream antioxidant protein expression (GCLC, HO-1) and attenuated oxidative stress (ROS, nitrite, GSH), neuroinflammation (NF-κB, TNF-α, IL-10), and neuronal apoptosis in the cerebral cortex and hippocampus of OKA-treated rats. Further, to determine whether modulation of Nrf2 signaling is responsible for the protective effect of sulforaphane, in vitro, Nrf2 siRNA and its downstream HO-1 inhibition studies were carried out in a rat astrocytoma cell line (C6). The protective effects of sulforaphane were abolished with Nrf2 siRNA and HO-1 inhibition in astrocytes. The results suggest that Nrf2-dependent activation of cellular antioxidant machinery results in sulforaphane-mediated protection against OKA-induced memory impairment in rats. Graphical Abstract ᅟ.

  12. Amelioration of Heat Stress Induced Disturbances of Antioxidant Defense System in Chicken by Brahma Rasayana

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    V. Ramnath

    2008-01-01

    Full Text Available Since the range of comfort zone or thermo neutral zone of domestic chickens is narrow, they become easily susceptible to heat and cold environmental stress. We evaluated Brahma Rasayana (BR supplementation on concentrations of certain oxidative stress markers associated with heat stress. A total of 48 egg type male chickens of local strain were divided into six groups (n = 8 for the study. Three groups were fed with BR orally at the rate of 2 g/kg bw daily for 10 days prior to and during the period of experiment. Two of the four groups that were exposed to heat stress (HST i.e. to a temperature of 40 ± 1°C and relative humidity of 80 ± 5% in an environmental chamber for 4 h daily for 5 or 10 days, received BR orally. The other two groups remained as BR treated and untreated non-heat stressed (NHST controls. There was a significant (P < 0.05 increase in the activities of antioxidant enzymes in blood such as catalase (CAT and superoxide dismutase (SOD, as well as liver CAT, glutathione peroxidase (GPX and glutathione reductase (GR in NHST-BR treated and HST-BR treated (both 5 and 10 days chickens when compared with untreated controls. A great deal of significant (P < 0.05 variations were seen in serum and liver reduced glutathione (GSH concentration in NHST-BR treated and HST-BR treated (both 5 and 10 days chickens. Serum and liver lipid peroxidation levels were found to be significantly (P < 0.05 higher in HST-untreated (both 5 and 10 days chickens when compared with other groups. Thus BR supplementation during HST brings about enhanced action of enzymatic and non-enzymatic antioxidants, which nullified the undesired side effects of free radicals that are generated during HST.

  13. Sericin ameliorated dysmorphic mitochondria in high-cholesterol diet/streptozotocin rat by antioxidative property.

    Science.gov (United States)

    Ampawong, Sumate; Isarangkul, Duangnate; Aramwit, Pornanong

    2017-02-01

    Sericin has been implicated in lower cholesterolemic effect due to its properties with several mechanisms. Mitochondria are one of the most important targets to be affected in high blood cholesterol and glucose conditions. The protective role of sericin on mitochondria remains doubtful. To examine this role, electron microscopic, histopathologic, immunohistochemical, and biochemical studies were performed in a high-cholesterol diet/streptozotocin rat model. The results demonstrated that sericin reduced blood cholesterol without hypoglycemic effect. Sericin alleviated dysmorphic mitochondria in heart and liver but not in kidney and also decreased peculiar endoplasmic reticulum in the exocrine pancreas. In addition, sericin decreased hepatic steatosis and preserved zymogen granule referable to the decline of reactive oxygen species production in hepatic mitochondrial extraction and down-regulation of malondialdehyde expression in the liver and exocrine pancreas however irrelevant to lipase activity. This study suggests that sericin has antioxidative property to reduce blood cholesterol by means of diminishing fat deposit in hepatocyte and improves mitochondria and endoplasmic reticulum integrities. [Box: see text].

  14. Antioxidant ameliorating effects against H2O2-induced cytotoxicity in primary endometrial cells.

    Science.gov (United States)

    Zal, F; Khademi, F; Taheri, R; Mostafavi-Pour, Z

    2018-02-01

    Oxidative stress and a disrupted antioxidant system are involved in a variety of pregnancy complications. In the present study, the role of vitamin E (Vit E) and folate as radical scavengers on the GSH homeostasis in stress oxidative induced in rat endometrial cells was investigated. Primary endometrial stromal cell cultures treated with 50 and 200 µM of H 2 O 2 and evaluated the cytoprotective effects of Vit E (5 µM) and folate (0.01 µM) in H 2 O 2 -treated cells for 24 h. Following the exposure of endometrial cells to H 2 O 2 alone and in the presence of Vit E and/or folate, cell survival, glutathione peroxidase (GPx) and glutathione reductase activities and the level of reduced glutathione (GSH) were measured. Cell adhesions comprise of cell attachment and spreading on collagen were determined. Flow cytometric analysis using annexin V was used to measure apoptosis. H 2 O 2 treatment showed a marked decrease in cell viability, GPx and GR activities and the level of GSH. Although Vit E or folate had some protective effect, combination therapy with Vit E and folate attenuated all the changes due to H 2 O 2 toxicity. An increasing number of alive cells was showed in the cells exposed to H 2 O 2 (50 µM) accompanied by co-treatment with Vit E and folic acid. The present findings indicate that co-administration of Vit E and folate before and during pregnancy may maintain a viable pregnancy and contribute to its clinical efficacy for the treatment of some idiopathic infertility.

  15. Catalytic Antioxidant Aeol 10150 Treatment Ameliorates Sulfur Mustard Analog 2-Chloroethyl Ethyl Sulfide Associated Cutaneous Toxic Effects

    Science.gov (United States)

    Tewari-Singh, Neera; Inturi, Swetha; Jain, Anil K.; Agarwal, Chapla; Orlicky, David J; White, Carl W.; Agarwal, Rajesh; Day, Brian J.

    2014-01-01

    Our previous studies and other published reports with the chemical warfare agent sulfur mustard (SM) and its analog 2-chloroethyl ethyl sulfide (CEES) have indicated a role of oxidative stress in skin injuries caused by these vesicating agents. We examined the effects of the catalytic antioxidant AEOL 10150 in attenuation of CEES-induced toxicity in our established skin injury models (skin epidermal cells and SKH-1 hairless mice) to validate the role of oxidative stress in the pathophysiology of mustard vesicating agents. Treatment of mouse epidermal JB6 and human HaCaT cells with AEOL 10150 (50 μM) 1 h post CEES exposure resulted in significant (p<0.05) reversal of CEES-induced decreases in both cell viability and DNA synthesis. Similarly, AEOL 10150 treatment 1 h after CEES exposure attenuated CEES-induced DNA damage in these cells. Similar AEOL 10150 treatments also caused significant (p<0.05) reversal of CEES-induced decreases in cell viability in normal human epidermal keratinocytes. Cytoplasmic and mitochondrial reactive oxygen species measurements showed that AEOL 10150 treatment drastically ameliorated the CEES-induced oxidative stress in both JB6 and HaCaT cells. Based on AEOL 10150 pharmacokinetic studies in SKH-1 mouse skin, mice were treated with topical formulation plus subcutaneous (injection; 5 mg/kg) AEOL 10150, 1 h after CEES (4 mg/mouse) exposure and every 4 h thereafter for 12 h. This AEOL 10150 treatment regimen resulted in over 50% (p<0.05) reversal in CEES-induced skin bi-fold and epidermal thickness, myeloperoxidase activity, and DNA oxidation in mouse skin. Results from this study demonstrate potential therapeutic efficacy of AEOL 10150 against CEES-mediated cutaneous lesions supporting AEOL 10150 as a medical countermeasure against SM-induced skin injuries. PMID:24815113

  16. The ameliorating effects of vitamin E on hepatic antioxidant system and xenobiotic-metabolizing enzymes in fenvalerate-exposed iodine-deficient rats.

    Science.gov (United States)

    Kocer-Gumusel, Belma; Erkekoglu, Pinar; Caglayan, Aydan; Hincal, Filiz

    2016-01-01

    This study investigated the effects of vitamin E (VE) on hepatic antioxidant system and drug-metabolizing enzymes in fenvalerate (FEN)-exposed iodine-deficient (ID) Wistar rats. ID was produced by perchlorate containing drinking water. VE was introduced by a loading dose of 100 mg/kg/d, i.g. for the first three days in the last week of feeding period; then with a single maintenance dose of 40 mg/kg on the 4th day. During last week, FEN groups (F) received 100 mg/kg/d, i.p. FEN. VE alone did not significantly affect thyroid hormones and antioxidant parameters; however, significantly increased total cytochrome P450 (38%) and cytochrome b5 levels (36%). In all ID groups, plasma thyroid-stimulating hormone (TSH) levels increased markedly, but remained at control level in vitamin E plus FEN receiving iodine-deficient group (IDVF) group. Glutathione peroxidase activity showed marked increases in F (19%) and FEN-exposed iodine-deficient group (IDF, 48%) groups. FEN treatment significantly increased total cytochrome P450 (28%) and thiobarbituric acid reactive substance levels (36%), as well as 7-ethoxyresorufin O-deethylase (120%), 7-penthoxyresorufin O-deethylase (139%) and glutathione S-transferase (15%) activities and decreased total glutathione concentrations (28%) versus control. Overall results suggest that vitamin E has ameliorating effects on the measured parameters in ID and/or FEN exposure.

  17. Antioxidants

    Science.gov (United States)

    Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Antioxidants are found in many foods, including fruits and ... are also available as dietary supplements. Examples of antioxidants include Beta-carotene Lutein Lycopene Selenium Vitamin A ...

  18. Schizandrin, an Antioxidant Lignan from Schisandra chinensis, Ameliorates Aβ1–42-Induced Memory Impairment in Mice

    Directory of Open Access Journals (Sweden)

    Di Hu

    2012-01-01

    Full Text Available In the present study, we examined the effect of schisandrin (SCH of Schisandra chinensis on the amyloid-beta1–42- (Aβ1–42- induced memory impairment in mice and elucidated the possible antioxidative mechanism. Mice were intracerebroventricular (i.c.v. injected with the aggregated Aβ1–42 and then treated with SCH (4, 12, and 36 mg/kg body weight or donepezil (DPZ, a reference drug (0.65 mg/kg by intragastric infusion for 14 days. Noncognitive disturbances and cognitive performance were evaluated by locomotor activity test, Y-maze test, and water maze test. Antioxidative enzyme activities including superoxide dismutase (SOD and glutathione peroxidase (GSH-px and levels of malondialdehyde (MDA, glutathione (GSH, and oxidized glutathione (GSSG within the cerebral cortex and hippocampus of mice were measured to elucidate the mechanism. Our results showed that SCH significantly improved Aβ1–42-induced short-term and spatial reference memory impairments in Y-maze test and water maze test. Furthermore, in the cerebral cortex and hippocampus of mice, SOD and GSH-px activities, GSH level, and GSH/GSSG ratio were increased, and levels of MDA and GSSG were decreased by the treatment of SCH. These results suggest that SCH is a potential cognitive enhancer against Alzheimer’s disease through antioxidative action.

  19. Synergistic antioxidant action of vitamin E and rutin SNEDDS in ameliorating oxidative stress in a Parkinson’s disease model

    Science.gov (United States)

    Sharma, Shrestha; Narang, Jasjeet K.; Ali, Javed; Baboota, Sanjula

    2016-09-01

    Purpose. Oxidative stress is the leading cause in the pathogenesis of Parkinson’s disease. Rutin is a naturally occurring strong antioxidant molecule with wide therapeutic applications. It suffers from the problem of low oral bioavailability which is due to its poor aqueous solubility. Methods. In order to increase the solubility self-nanoemulsifying drug delivery systems (SNEDDS) of rutin were prepared. The oil, surfactant and co-surfactant were selected based on solubility/miscibility studies. Optimization was done by a three-factor, four-level (34) Box-Behnken design. The independent factors were oil, surfactant and co-surfactant concentration and the dependent variables were globule size, self-emulsification time, % transmittance and cumulative percentage of drug release. The optimized SNEDDS formulation (RSE6) was evaluated for various release studies. Antioxidant activity was assessed by various in vitro tests such as 2,2-diphenyl-1-picrylhydrazyl and reducing power assay. Oxidative stress models which had Parkinson’s-type symptoms were used to determine the antioxidant potential of rutin SNEDDS in vivo. Permeation was assessed through confocal laser scanning microscopy. Results. An optimized SNEDDS formulation consisting of Sefsol + vitamin E-Solutol HS 15-Transcutol P at proportions of 25:35:17.5 (w/w) was prepared and characterized. The globule size and polydispersity index of the optimized formulation was found to be 16.08 ± 0.02 nm and 0.124 ± 0.01, respectively. A significant (p disorders like Parkinson’s disease.

  20. Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus.

    Science.gov (United States)

    Jangra, Ashok; Kasbe, Prajapati; Pandey, Surya Narayan; Dwivedi, Shubham; Gurjar, Satendra S; Kwatra, Mohit; Mishra, Murli; Venu, Athira K; Sulakhiya, Kunjbihari; Gogoi, Ranadeep; Sarma, Nitul; Bezbaruah, Babul K; Lahkar, Mangala

    2015-12-01

    Mounting evidence suggests that long-term aluminum exposure results in severe toxic effects, including neurobehavioral and neurochemical anomalies. The present study was performed to examine the neuroprotective potential of hesperidin and silibinin against aluminum chloride (AlCl3)-induced neurotoxicity in mice. AlCl3 (100 mg/kg/day) was injected daily through oral gavage for 42 days. Concomitantly, hesperidin (50 and 100 mg/kg/day, p.o.) and silibinin (100 and 200 mg/kg/day, p.o.) was administered for 42 days in different groups. The extent of cognitive impairment was assessed by Morris water maze and novel object recognition test on the 43rd day. Neurotoxicity was assessed by measuring oxido-nitrosative stress and proinflammatory cytokines in the hippocampus of mice. Six weeks treatment with AlCl3 caused cognitive impairment as indicated by an increase in the retention latency time and reduction in the percentage of recognition index. AlCl3-treated group showed oxido-nitrosative stress as indicated by increase in the level of lipid peroxidation, nitrite and depleted reduced glutathione, catalase activity in the hippocampus. Moreover, the chronic AlCl3 administration raised the proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) level and increased acetylcholinesterase activity and reduced the BDNF content in the hippocampus of AlCl3-treated animals. However, chronic treatment with hesperidin and silibinin at higher doses significantly ameliorated the AlCl3-induced cognitive impairment and hippocampal biochemical anomalies. The present study clearly indicated that hesperidin and silibinin exert neuroprotective effects against AlCl3-induced cognitive impairment and neurochemical changes. Amelioration of cognitive impairment may be attributed to the impediment of oxido-nitrosative stress and inflammation in the hippocampus.

  1. Withania somnifera Leaf Extract Ameliorates Benzo[a]pyrene-Induced Behavioral and Neuromorphological Alterations by Improving Brain Antioxidant Status in Zebrafish (Danio rerio).

    Science.gov (United States)

    Mohanty, Ratnalipi; Das, Saroj Kumar; Singh, Nihar Ranjan; Patri, Manorama

    2016-06-01

    The aquatic environment provides a sink for the environmental pollutants that have potential to induce oxidative stress by altering neurobehavioral response of aquatic animals. Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon is known to induce oxidative stress in the brain. Withania somnifera has been used traditionally for its neuroprotective effect in experimental models of neurological disorders. The present study is aimed to evaluate the neuroprotective potential of Withania somnifera leaf extract (WSLE) following exposure to waterborne B[a]P. Wild-type zebrafish (Danio rerio) were designated as naive, control (dimethyl sulfoxide), WSLE, B[a]P, and B[a]P + WSLE groups. Behavioral studies showed reversal in scototaxis (anxiety-like) behavior in B[a]P group and was restored by WSLE cosupplementation in B[a]P + WSLE group. B[a]P-induced altered antioxidant status was ameliorated by WSLE in the B[a]P + WSLE group. Previous studies showed that the periventricular gray zone (PGZ) of the optic tectum in zebrafish brain regulates scototaxis (anxiety-like) behavior. Our histopathological observation showed a significant increase in the pyknotic neuronal counts in PGZ of the B[a]P group and was ameliorated by WSLE cosupplementation. The study showed that the reversal in scototaxis behavior following exposure to waterborne B[a]P might be associated with neuromorphological alterations in PGZ, whereas a pioneer ethnopharmacological approach of WSLE cosupplementation showed its neuroprotective role to restore normal scototaxis of zebrafish. Future research directing toward understanding the role of visual circuit involved with impaired scototaxis behavior in zebrafish might provide new pathological outcomes following exposure to B[a]P.

  2. Amelioration of Colitis in Mouse Model by Exploring Antioxidative Potentials of an Indigenous Probiotic Strain of Lactobacillus fermentum Lf1

    Directory of Open Access Journals (Sweden)

    Ritu Chauhan

    2014-01-01

    Full Text Available Based on the preliminary screening of eight indigenous putative probiotic Lactobacilli, Lactobacillus fermentum Lf1 was selected for assessing its antioxidative efficacy in DSS colitis mouse model based on its ability to enhance the expression of “Nrf2” by 6.43-fold and malondialdehyde (MDA inhibition by 78.1  ±  0.24% in HT-29 cells under H2O2 stress. The Disease Activity Index and histological scores of Lf1-treated mice were lower than the control group. However, expression of “Nrf2” was not observed in Lf1-treated mice. A significant increase in the expression of antioxidative enzymes such as SOD2 and TrxR-1 was recorded in both of the groups. The expression of SOD2 was significantly downregulated in colitis-induced mice by −100.00-fold relative to control group, and the downregulation was considerably reduced to −37.04-fold in colitis Lf1 treatment group. Almost, a similar trend was recorded in case of “thioredoxin” expression, though “CAT” was refractile to expression. The Lf1-treated group had decreased malondialdehyde level as compared to colitis control (37.92  ±  6.31 versus 91.13  ±  5.76 μM/g. These results point towards Lf1-induced activation of the antioxidant enzyme system in the mouse model and its prospects to be explored as a new strategy for IBD management.

  3. The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk.

    Directory of Open Access Journals (Sweden)

    Denis N Silachev

    Full Text Available BACKGROUND: Many ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies. METHODOLOGY/PRINCIPAL FINDINGS: We used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3β (GSK-3β in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3β in brain. Co-cultivation of SkQR1-treated

  4. Involvement of Antioxidant System in the Amelioration of Scopolamine-Induced Memory Impairment by Grains of Paradise (Aframomum melegueta K. Schum.) Extract.

    Science.gov (United States)

    Ishola, I O; Awoyemi, A A; Afolayan, G O

    2016-09-01

    Background: Grains of paradise ( Aframomum melegueta ) K. Schum is used to flavour foods and used as memory enhancer and anti-aging in traditional African medicine. This study examine the influence of ethanolic seed extract of Aframomum melegueta (AFM) on cognitive impairment induced by scopolamine in rodents. Methods: AFM (6.25, 12.5 or 25 mg/kg, p.o .) or tacrine (5 mg/kg, i.p .) was administered for 3 consecutive days, 1 h post-treatment on day 3, scopolamine (3 mg/kg, i.p .) was given, 5 min later, cognition was evaluated in the Y-maze and elevated plus maze (EPM) tests in mice as well as the Morris water maze (MWM) paradigm in rats. Biomarkers of oxidative stress in the prefrontal cortex, striatum and hippocampus of rats were evaluated after the MWM task. The antioxidant capacity of AFM was evaluated in vitro using the 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO) and ferric ion reducing power (FRAP) assays. Results: Scopolamine significantly reduced (38.72%) spontaneous alternation behavior in the Y-maze and increase in transfer latency in the EPM test on day 2, which was ameliorated by AFM (25 mg/kg; 49.86%, 71.55%, respectively) in mice. In addition, AFM prevented the spatial learning deficit induced by scopolamine in the MWM task. Similarly, scopolamine-induced oxidative-nitrosative stress was attenuated by AFM treatment, evidenced in decreased malondialdehyde and nitrite levels, restoration of glutathione and superoxide dismutase levels. Interestingly, AFM exhibited notable scavenging activities against DPPH, NO and FRAP radicals. Conclusion: These results showed that A. melegueta seed extract prevented scopolamine-induced memory impairments through enhancement of antioxidant defense systems. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Ameliorating Effects of Bacillus subtilis ANSB060 on Growth Performance, Antioxidant Functions, and Aflatoxin Residues in Ducks Fed Diets Contaminated with Aflatoxins

    Directory of Open Access Journals (Sweden)

    Liyuan Zhang

    2016-12-01

    Full Text Available Bacillus subtilis ANSB060 isolated from fish gut is very effective in detoxifying aflatoxins in feed and feed ingredients. The purpose of this research was to investigate the effects of B. subtilis ANSB060 on growth performance, body antioxidant functions, and aflatoxin residues in ducks fed moldy maize naturally contaminated with aflatoxins. A total of 1500 18-d-old male Cherry Valley ducks with similar body weight were randomly assigned to five treatments with six replicates of 50 ducks per repeat. The experiment design consisted of five dietary treatments labeled as C0 (basal diet containing 60% normal maize, M0 (basal diet containing 60% moldy maize contaminated with aflatoxins substituted for normal maize, M500, M1000, and M2000 (M0 +500, 1000 or 2000 g/t aflatoxin biodegradation preparation mainly consisted of B. subtilis ANSB060. The results showed that ducks fed 22.44 ± 2.46 μg/kg of AFB1 (M0 exhibited a decreasing tendency in average daily gain (ADG and total superoxide dismutase (T-SOD activity in serum, and T-SOD and glutathione peroxidase (GSH-Px activities in the liver significantly decreased along with the appearance of AFB1 and AFM1 compared with those in Group C0. The supplementation of B. subtilis ANSB060 into aflatoxin-contaminated diets increased the ADG of ducks (p > 0.05, significantly improved antioxidant enzyme activities, and reduced aflatoxin accumulation in duck liver. In conclusion, Bacillus subtilis ANSB060 in diets showed an ameliorating effect to duck aflatoxicosis and may be a promising feed additive.

  6. Ameliorating Effects of Bacillus subtilis ANSB060 on Growth Performance, Antioxidant Functions, and Aflatoxin Residues in Ducks Fed Diets Contaminated with Aflatoxins.

    Science.gov (United States)

    Zhang, Liyuan; Ma, Qiugang; Ma, Shanshan; Zhang, Jianyun; Jia, Ru; Ji, Cheng; Zhao, Lihong

    2016-12-22

    Bacillus subtilis ANSB060 isolated from fish gut is very effective in detoxifying aflatoxins in feed and feed ingredients. The purpose of this research was to investigate the effects of B. subtilis ANSB060 on growth performance, body antioxidant functions, and aflatoxin residues in ducks fed moldy maize naturally contaminated with aflatoxins. A total of 1500 18-d-old male Cherry Valley ducks with similar body weight were randomly assigned to five treatments with six replicates of 50 ducks per repeat. The experiment design consisted of five dietary treatments labeled as C0 (basal diet containing 60% normal maize), M0 (basal diet containing 60% moldy maize contaminated with aflatoxins substituted for normal maize), M500, M1000, and M2000 (M0 +500, 1000 or 2000 g/t aflatoxin biodegradation preparation mainly consisted of B. subtilis ANSB060). The results showed that ducks fed 22.44 ± 2.46 μg/kg of AFB₁ (M0) exhibited a decreasing tendency in average daily gain (ADG) and total superoxide dismutase (T-SOD) activity in serum, and T-SOD and glutathione peroxidase (GSH-Px) activities in the liver significantly decreased along with the appearance of AFB₁ and AFM₁ compared with those in Group C0. The supplementation of B. subtilis ANSB060 into aflatoxin-contaminated diets increased the ADG of ducks ( p > 0.05), significantly improved antioxidant enzyme activities, and reduced aflatoxin accumulation in duck liver. In conclusion, Bacillus subtilis ANSB060 in diets showed an ameliorating effect to duck aflatoxicosis and may be a promising feed additive.

  7. Assessment of Antioxidant Enzyme Activity and Mineral Nutrients in Response to NaCl Stress and its Amelioration Through Glutathione in Chickpea.

    Science.gov (United States)

    Shankar, Vinay; Kumar, Dinesh; Agrawal, Veena

    2016-01-01

    Salinity stress has been reckoned as one of the major threat towards crop productivity as it causes significant decline in the yield. The impact of NaCl stress (0, 1, 10, 50, 100 and 200 mg L(-1)) as well as glutathione (10 mg L(-1)) either alone or in combination has been evaluated on the induction of multiple shoots, antioxidant enzymes' activity, lipid peroxidation, relative permeability, concentration of nutrients, photosynthetic pigments, protein and proline content of nodal segments of chickpea after 14 days of culture. The antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX) and glutathione reductase (GR) were found to be increased under salt stress as well as glutathione-supplemented medium. A significant decrease in the concentrations of chlorophylls a, b, total chlorophyll and carotenoid was observed under salt stress. Concentrations of nitrogen, phosphorus, potassium, calcium, carbon, magnesium and sulphur showed an initial increase up to 10 mg L(-1) NaCl, but a decline was seen at higher NaCl levels. Proline content and malondialdehyde concentration were found to be increased under salt stress. Three isoforms of SOD, one of CAT and four of GPX were expressed during native polyacrylamide gel electrophoresis (PAGE) analysis. However, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the stressed nodal explants revealed the over-expression of several polypeptide bands related to NaCl stress. These findings for the first time suggest that glutathione (GSH) helps in ameliorating NaCl stress in nodal explants of chickpea by manipulating various biochemical and physiological responses of plants.

  8. Acupuncture ameliorates cognitive impairment and hippocampus neuronal loss in experimental vascular dementia through Nrf2-mediated antioxidant response.

    Science.gov (United States)

    Wang, Xue-Rui; Shi, Guang-Xia; Yang, Jing-Wen; Yan, Chao-Qun; Lin, Li-Ting; Du, Si-Qi; Zhu, Wen; He, Tian; Zeng, Xiang-Hong; Xu, Qian; Liu, Cun-Zhi

    2015-12-01

    Emerging evidence suggests acupuncture could exert neuroprotection in the vascular dementia via anti-oxidative effects. However, the involvement of Nrf2, a master regulator of antioxidant defense, in acupuncture-induced neuroprotection in vascular dementia remains undetermined. The goal of our study was to investigate the contribution of Nrf2 in acupuncture and its effects on vascular dementia. Morris water maze and Nissl staining were used to assess the effect of acupuncture on cognitive function and hippocampal neurodegeneration in experimental vascular dementia. The distribution of Nrf2 in neurons in hippocampus, the protein expression of Nrf2 in both cytosol and nucleus, and the protein and mRNA levels of its downstream target genes NQO1 and HO-1 were detected by double immunofluorescent staining, Western blotting and realtime PCR analysis respectively. Cognitive function and microglia activation were measured in both wild-type and Nrf2 gene knockout mice after acupuncture treatment. We found that acupuncture could remarkably reverse the cognitive deficits, neuron cell loss, reactive oxygen species production, and decreased cerebral blood flow. It was notable that acupuncture enhanced nuclear translocation of Nrf2 in neurons and up-regulate the protein and mRNA levels of Nrf2 and its target genes HO-1 and NQO1. Moreover, acupuncture could significantly down-regulated the over-activation of microglia after common carotid artery occlusion surgery. However, the reversed cognitive deficits, neuron cell loss and microglia activation by acupuncture were abolished in Nrf2 gene knockout mice. In conclusion, these findings provide evidence that the neuroprotection of acupuncture in models of vascular dementia was via the Nrf2 activation and Nrf2-dependent microglia activation. Copyright © 2015. Published by Elsevier Inc.

  9. Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage

    OpenAIRE

    Gonz?lez-Ponce, Herson Antonio; Mart?nez-Salda?a, Mar?a Consolaci?n; Rinc?n-S?nchez, Ana Rosa; Sumaya-Mart?nez, Mar?a Teresa; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han; Jaramillo-Ju?rez, Fernando

    2016-01-01

    Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-L-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts agai...

  10. Dietary flaxseed oil supplementation ameliorates the effect of cisplatin on brush border membrane enzymes and antioxidant system in rat intestine.

    Science.gov (United States)

    Naqshbandi, A; Rizwan, S; Khan, M W; Khan, F

    2013-04-01

    Cisplatin (CP; cis-diamminedichloroplatinum II) is a drug widely used against different types of solid tumors. Patients receiving CP, however, experience very profound and long lasting gastrointestinal symptoms. Recently, ω-3 polyunsaturated fatty acid-enriched flaxseed/flaxseed oil (FXO) has shown numerous health benefits. The present study was undertaken to investigate whether FXO can prevent CP-induced adverse biochemical changes in the small intestine of rats. A single intraperitoneal dose of CP (6 mg/kg body weight) was administered to male Wistar rats fed with control diet (CP group) and FXO diet (CPFXO group). Administration of CP led to a significant decline in the specific activities of brush border membrane enzymes both in the mucosal homogenates and in the isolated membrane vesicles. Lipid peroxidation and total sulfhydryl groups were altered upon CP treatment, indicating the generation of oxidative stress. The activities of SOD, catalase and glutathione peroxidase also decreased in CP-treated rats. In contrast, dietary supplementation of FXO prior to and following CP treatment significantly attenuated the CP-induced changes in all these parameters. FXO feeding markedly enhanced resistance to CP-elicited adverse gastrointestinal effects. The results suggest that FXO owing to its intrinsic biochemical/antioxidant properties is an effective agent in reducing the adverse effects of CP on intestine.

  11. EVALUATION OF THE POSSIBLE ANTIOXIDANT EFFECTS OF NIGELLA SATIVA AND CURCUMA LONGA IN AMELIORATING DIABETIC NEPHROPATHY IN RATS

    International Nuclear Information System (INIS)

    OSMAN, N.N.; FARAG, M.F.S.; DARWISH, M.M

    2009-01-01

    Chronic hyperglycemia in diabetes leads to the overproduction of free radicals and the evidence is increasing because these radicals are responsible for the development of diabetic nephropathy. Diabetic nephropathy is an important microvascular complication and one of the main causes of end stage renal disease. The aim of the present study was to test the hypothesis that combined treatment with Nigella sativa (NS) and Curcuma longa (CL) is more effective than each of them alone in improving renal function and oxidative stress in alloxan-induced diabetic rats.Diabetes was induced in male albino rats with a single intravenous injection of alloxan (150 mg/kg). Two weeks after alloxan injection, rats were divided into five groups; control, diabetic and diabetic rats received either NS (10ml/kg/day), or CL (80mg/kg/day) and their combination by gastric intubation for 4 weeks.Diabetic rats exhibited many symptoms including loss of body weight, hyperglycemia, polyuria, renal enlargement and renal dysfunction. Significant increase in TBARS (lipid peroxidation marker) was observed in diabetic kidney. This was accompanied by a significant decrease in GSH content, SOD and CAT activities in the kidneys. Daily oral ingestion of NS and/or CL extract for 4 weeks has attenuated the oxidative stress in the kidney and reversed the adverse effect of diabetes in rats by lowering blood glucose levels, increased plasma insulin and restored body weight loss and renal function.These results confirm the role of oxidative stress in the development of diabetic nephropathy and point to the possible anti-oxidative mechanism being responsible for the nephroprotective action of NS and CL.

  12. Fraxetin and ethyl acetate extract from Lawsonia inermis L. ameliorate oxidative stress in P. berghei infected mice by augmenting antioxidant defence system.

    Science.gov (United States)

    Singh, Dhananjay Kumar; Cheema, Harveer Singh; Saxena, Archana; Jyotshana; Singh, Shilpi; Darokar, Mahendra P; Bawankule, Dnyaneshwar U; Shanker, Karuna; Luqman, Suaib

    2017-12-01

    Lawsonia inermis L. is a well-documented plant for cosmetic as well as medicinal properties. It is used by local communities in India and Nigeria for the treatment of many parasitic diseases, including malaria. Earlier studies on the plant's antiplasmodial activity were not assigned to any phytochemical with no quality assurance data. In this report, a recent chemically characterized extract and it's major constituent were investigated for in vitro antiplasmodial activity on chloroquine sensitive NF-54 strain. Furtherly, the potent extract and this constituent were assessed in vivo in Plasmodium berghei infected mice. The bioactive phytochemical and enriched extract were also monitored against various oxidative stress parameters. The extract characterization was done by the quantitative analysis of eight phytochemicals using gradient reverse phase HPLC method. In vitro antiplasmodial activity was evaluated on chloroquine sensitive NF-54 strain by the determination of pfLDH activity. In vivo activity of the most potent extract and constituent were evaluated in P. berghei infected mice upon oral administration. The estimation of oxidative stress was done by monitoring various enzymatic and non-enzymatic parameters. The ethyl acetate extract of leaves (IC 50 9.00 ± 0.68 µg/ml) and fraxetin (IC 50 19.21 ± 1.04 µM) were the most effective in in vitro assays therefore selected for in vivo tests. The administration of the ethyl acetate extract of leaves and fraxetin to the infected mice resulted in significant (p ethyl acetate extract of L. inermis and fraxetin were able to suppress the oxidative damage by augmenting endogenous antioxidant system and thus ameliorated the plasmodium infection in mice. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

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    Yihan Zhang

    2016-01-01

    Full Text Available Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R after high (25 mM or low (5.5 mM glucose culture. Cell viability, reactive oxygen species (ROS, and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2 and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

  14. Supplemental Antioxidants Do Not Ameliorate Colitis Development in HLA-B27 Transgenic Rats Despite Extremely Low Glutathione Levels in Colonic Mucosa

    NARCIS (Netherlands)

    Schepens, M.A.A.; Vink, C.; Schonewille, A.J.; Roelofs, H.M.J.; Brummer, R.J.; Meer, van der R.; Bovee-Oudenhoven, I.M.J.

    2011-01-01

    Background: Oxidative stress is presumed to play an important role in inflammatory bowel disease (IBD). Accordingly, antioxidant supplementation might be protective. Dietary calcium inhibited colitis development in HLA-B27 transgenic rats, an animal model mimicking IBD. As antioxidants might act at

  15. Oral Nigella sativa oil and thymoquinone administration ameliorates the effect of long-term cisplatin treatment on the enzymes of carbohydrate metabolism, brush border membrane, and antioxidant defense in rat intestine.

    Science.gov (United States)

    Shahid, Faaiza; Farooqui, Zeba; Khan, Aijaz Ahmed; Khan, Farah

    2018-02-01

    We have previously shown that oral administration of Nigella sativa oil (NSO) ameliorates the deleterious gastrointestinal effects of cisplatin (CP), administered as a single dose. Since a typical clinical CP dosing regimen involves multiple cycles of CP administration in lower doses, in the present study we investigate the protective efficacy of NSO and its major bioactive constituent, thymoquinone (TQ), against multiple-dose CP treatment-induced deleterious biochemical and histological changes in rat intestine. Rats were divided into six groups, viz., control, CP, CP+NSO, CP+TQ, NSO, and TQ. Animals in CP+NSO and CP+TQ groups were pre-administered NSO (2 ml/kg bwt, orally) and TQ (1.5 mg/kg bwt, orally), respectively, daily for 14 days and were then treated with five repeated doses of CP (3 mg/kg bwt, i.p.), every fourth day for 20 days while still receiving NSO/TQ. CP treatment alone led to a significant decline in specific activities of brush border membrane (BBM) enzymes while NSO or TQ administration to CP-treated rats significantly prevented the decline in BBM enzyme activities in the isolated brush border membrane vesicles (BBMV) as well as in mucosal homogenates. Furthermore, both NSO and TQ administration markedly ameliorated CP-induced alterations on carbohydrate metabolism enzymes and the enzymatic and non-enzymatic parameters of antioxidant defense system in the intestinal mucosa. However, NSO appeared to be more efficacious than TQ in protecting against CP-induced gastrointestinal dysfunction. Histopathological findings corroborated the biochemical results. Thus, NSO and TQ may prove clinically useful in amelioration of the intestinal toxicity associated with long-term CP chemotherapy.

  16. Effects of foliar dressing of selenite and silicate alone or combined with different soil ameliorants on the accumulation of As and Cd and antioxidant system in Brassica campestris.

    Science.gov (United States)

    Ding, Yongzhen; Wang, Yongjiu; Zheng, Xiangqun; Cheng, Weimin; Shi, Rongguang; Feng, Renwei

    2017-08-01

    This study was conducted to investigate the possibility of using a combined technology to synchronously reduce As and Cd accumulation in the edible parts of Brassica campestris. The results showed that a foliar application of selenite (Se) and silicon (Si) combined with soil ameliorants (including Ca-Mg-P fertilizer, sodium silicate and red mud) showed limited effects on the growth of B. campestris. The As concentration in the leaves of B. campestris in all treatments was below the Chinese safety standard. When sodium silicate and Ca-Mg-P fertilizer were added to the soil, the additional foliar application of Se and Si could in some cases help further reduce the concentrations of As and Cd in the leaves of B. campestris. However, when red mud was applied to the soil, the foliar application of Se and Si enhanced the Cd concentration in the leaves of B. campestris. In most cases, high levels of soil ameliorants plus foliar application of Se and Si significantly enhanced the As concentrations in both the soil solution and the roots of B. campestris but reduced the soil solution Cd concentration and the leaf As concentration. Most of the treatments reduced the thiobarbituric acid reactive substances (TBARS) concentration in the leaves of B. campestris, and the foliar application of Se and Si helped the soil ameliorants alleviate the oxidative stress resulting from As and Cd exposure. In this study, several treatments significantly increased the activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX). However, the enzymes peroxidase (POD) and catalase (CAT) were not induced by most treatments. In summary, the combined treatment of 1gkg -1 Ca-Mg-P fertilizer plus foliar spraying 2mmolL -1 sodium selenite was most effective in reducing the Cd concentration and a rather strong ability to reduce the As concentration and trigger the activities of SOD and APX in the leaves of B. campestris. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. α-lipoic acid ameliorates n-3 highly-unsaturated fatty acids induced lipid peroxidation via regulating antioxidant defenses in grass carp (Ctenopharyngodon idellus).

    Science.gov (United States)

    Shi, Xiao-Chen; Jin, Ai; Sun, Jian; Yang, Zhou; Tian, Jing-Jing; Ji, Hong; Yu, Hai-Bo; Li, Yang; Zhou, Ji-Shu; Du, Zhen-Yu; Chen, Li-Qiao

    2017-08-01

    This study evaluated the protective effect of α-lipoic acid (LA) on n-3 highly unsaturated fatty acids (HUFAs)-induced lipid peroxidation in grass carp. The result indicated that diets with n-3 HUFAs increased the production of malondialdehyde (MDA) (P fatty acid composition of muscle and liver (P < 0.05). Furthermore, LA significantly promoted the activity of antioxidant enzymes in serum, muscle and liver of grass carp (P < 0.05), including superoxide dismutase (SOD), catalase (CAT), and glutathione s-transferase (GST). The further results showed that LA significantly elevated mRNA expression of antioxidant enzymes with promoting the mRNA expression of NF-E2-related nuclear factor 2 (Nrf2) and decreasing Kelch-like-ECH-associated protein 1 (Keap1) mRNA level. From the above, these results suggested that LA could attenuate n-3 HUFAs-induced lipid peroxidation, remit the toxicity of the lipid peroxidant, and protect n-3 HUFAs against lipid peroxidation to promote its deposition in fish, likely strengthening the activity of antioxidant enzymes through regulating mRNA expressions of antioxidant enzyme genes via mediating Nrf2-Keap1 signaling pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. A Regenerative Antioxidant Protocol of Vitamin E and α-Lipoic Acid Ameliorates Cardiovascular and Metabolic Changes in Fructose-Fed Rats

    Directory of Open Access Journals (Sweden)

    Jatin Patel

    2011-01-01

    Full Text Available Type 2 diabetes is a major cause of cardiovascular disease. We have determined whether the metabolic and cardiovascular changes induced by a diet high in fructose in young adult male Wistar rats could be prevented or reversed by chronic intervention with natural antioxidants. We administered a regenerative antioxidant protocol using two natural compounds: α-lipoic acid together with vitamin E (α-tocopherol alone or a tocotrienol-rich fraction, given as either a prevention or reversal protocol in the food. These rats developed glucose intolerance, hypertension, and increased collagen deposition in the heart together with an increased ventricular stiffness. Treatment with a fixed combination of vitamin E (either α-tocopherol or tocotrienol-rich fraction, 0.84 g/kg food and α-lipoic acid (1.6 g/kg food normalized glucose tolerance, blood pressure, cardiac collagen deposition, and ventricular stiffness in both prevention and reversal protocols in these fructose-fed rats. These results suggest that adequate antioxidant therapy can both prevent and reverse the metabolic and cardiovascular damage in type 2 diabetes.

  19. C1q/TNF-Related Protein-9 Ameliorates Ox-LDL-Induced Endothelial Dysfunction via PGC-1α/AMPK-Mediated Antioxidant Enzyme Induction

    Directory of Open Access Journals (Sweden)

    Haijian Sun

    2017-05-01

    Full Text Available Oxidized low-density lipoprotein (ox-LDL accumulation is one of the critical determinants in endothelial dysfunction in many cardiovascular diseases such as atherosclerosis. C1q/TNF-related protein 9 (CTRP9 is identified to be an adipocytokine with cardioprotective properties. However, the potential roles of CTRP9 in endothelial function remain largely elusive. In the present study, the effects of CTRP9 on the proliferation, apoptosis, migration, angiogenesis, nitric oxide (NO production and oxidative stress in human umbilical vein endothelial cells (HUVECs exposed to ox-LDL were investigated. We observed that treatment with ox-LDL inhibited the proliferation, migration, angiogenesis and the generation of NO, while stimulated the apoptosis and reactive oxygen species (ROS production in HUVECs. Incubation of HUVECs with CTRP9 rescued ox-LDL-induced endothelial injury. CTRP9 treatment reversed ox-LDL-evoked decreases in antioxidant enzymes including heme oxygenase-1 (HO-1, nicotinamide adenine dinucleotide phosphate (NAD(PH dehydrogenase quinone 1, and glutamate-cysteine ligase (GCL, as well as endothelial nitric oxide synthase (eNOS. Furthermore, CTRP9 induced activation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC1-α and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK. Of interest, AMPK inhibition or PGC1-α silencing abolished CTRP9-mediated antioxidant enzymes levels, eNOS expressions, and endothelial protective effects. Collectively, we provided the first evidence that CTRP9 attenuated ox-LDL-induced endothelial injury by antioxidant enzyme inductions dependent on PGC-1α/AMPK activation.

  20. Oral administration of caffeic acid ameliorates the effect of cisplatin on brush border membrane enzymes and antioxidant system in rat intestine.

    Science.gov (United States)

    Arivarasu, N A; Priyamvada, Shubha; Mahmood, Riaz

    2013-01-01

    Cisplatin (CP) is a widely used antineoplastic drug that exhibits gastrointestinal toxicity. We have previously shown that administration of a single dose of CP results in a decrease in the activities of several brush border membrane (BBM) enzymes, induces oxidative stress and alters the activities of several antioxidant enzymes in the small intestine of rats. In the present study we have investigated the effect of treatment with the dietary antioxidant caffeic acid (CA) on CP induced biochemical changes in the intestine. Administration of a single intraperitoneal dose of CP alone (6 mg/kg body weight) led to a decrease in the activities of the BBM enzymes, increase in lipid peroxidation, decrease in sulfhydryl groups and changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, glucose 6-phosphate dehydrogenase, glutathione reductase, glutathione S-transferase and thioredoxin reductase. Administration of two doses of CA (each of 250 mg/kg body weight), at 15 and 120 min after treatment with CP, significantly attenuated the CP-induced changes in all these parameters but the administration of CA alone had no effect. These results suggest that CA is an effective agent in reducing the effects of CP on the intestine and could prove to be useful in alleviating the gastrointestinal toxicity of this drug. Copyright © 2011 Elsevier GmbH. All rights reserved.

  1. Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on brush border membrane enzymes, carbohydrate metabolism and antioxidant system in rat intestine.

    Science.gov (United States)

    Shahid, Faaiza; Farooqui, Zeba; Rizwan, Sana; Abidi, Subuhi; Parwez, Iqbal; Khan, Farah

    2017-06-14

    Cisplatin (CP) is an effective chemotherapeutic agent that induces gastrointestinal toxicity. Nigella sativa oil (NSO) has been shown to be beneficial in a wide range of gastrointestinal disorders. The present study investigates the possible protective effect of NSO on CP-induced gastrointestinal toxicity. NSO administration (2ml/kg bwt, orally), prior to and following, a single dose CP treatment (6mg/kg bwt. ip), significantly attenuated the CP-induced decrease in brush border membrane (BBM) enzyme activities in intestinal homogenates and BBM vesicles (BBMV). NSO administration also mitigated CP induced alterations in the activities of carbohydrate metabolism enzymes and in the enzymatic and non-enzymatic antioxidant parameters in the intestine. The results suggest that NSO by empowering the endogenous antioxidant system improves intestinal redox and metabolic status and restores BBM integrity in CP treated rats. Histopathological studies supported the biochemical findings. Thus, NSO may help prevent the accompanying gastrointestinal dysfunction in CP chemotherapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. Hyperglycemia-induced oxidative stress induces apoptosis by inhibiting PI3-kinase/Akt and ERK1/2 MAPK mediated signaling pathway causing downregulation of 8-oxoG-DNA glycosylase levels in glial cells.

    Science.gov (United States)

    Kumar, Premranjan; Rao, G Nageswar; Pal, Bibhuti Bhusan; Pal, Arttatrana

    2014-08-01

    Glial cells are very important for normal brain function and alterations in their activity due to hyperglycemia, could contribute to diabetes-related cognitive dysfunction. Oxidative insults often cause rapid changes in almost all cells including glial cells. However, pathophysiologic mechanisms that lead to diabetic complications are not completely elucidated. Therefore, we examined whether elevated glucose levels directly or indirectly disrupt antioxidant defense mechanisms causing alterations in signaling pathways, cell cycle dysregulation, and reactive oxygen/nitrogen species-mediated apoptosis in glial cells. Findings of this study demonstrated that exposure of glial cells to high glucose markedly induces cellular and molecular injuries, as evidenced by elevated levels of reactive oxygen/nitrogen species, biomolecules damage, cell cycle dysregulation, decrease in antioxidant enzymes, and decrease in cell viability. Pretreatment of cells with N-acetyl-L-cysteine reduced high glucose-induced cytotoxicity by increasing the levels of antioxidant enzymes, and decreasing the number of apoptotic cells. Further, at molecular level high glucose treatment resulted in a significant increase in phosphorylation of Akt, MAPKs, tuberin, down regulation of 8-oxoG-DNA glycosylase and increase in 8-hydroxydeoxyguanosine accumulations. Pretreatment of cells with N-acetyl-L-cysteine, phosphatidylinositol3-kinase/Akt and ERK1/2 inhibitors completely abolished the apoptotic effects of high glucose. Moreover, N-acetyl-L-cysteine significantly inhibited reactive oxygen/nitrogen species generation, elevated antioxidants levels, inhibited Akt, ERK1/2, tuberin phosphorylation, decreased 8-hydroxydeoxyguanosine accumulation and upregulated 8-oxoG-DNA glycosylase expression. Our results demonstrate that high glucose induces apoptosis and inhibits proliferation of glial cells, which may be mediated by the phosphorylation of tuberin, down regulation of 8-oxoG-DNA glycosylase and 8

  3. Ameliorative effect of fisetin on cisplatin-induced nephrotoxicity in rats via modulation of NF-κB activation and antioxidant defence.

    Directory of Open Access Journals (Sweden)

    Bidya Dhar Sahu

    Full Text Available Nephrotoxicity is a dose-dependent side effect of cisplatin limiting its clinical usage in the field of cancer chemotherapy. Fisetin is a bioactive flavonoid with recognized antioxidant and anti-inflammatory properties. In the present study, we investigated the potential renoprotective effect and underlying mechanism of fisetin using rat model of cisplatin-induced nephrotoxicity. The elevation in serum biomarkers of renal damage (blood urea nitrogen and creatinine; degree of histopathological alterations and oxidative stress were significantly restored towards normal in fisetin treated, cisplatin challenged animals. Fisetin treatment also significantly attenuated the cisplatin-induced IκBα degradation and phosphorylation and blocked the NF-κB (p65 nuclear translocation, with subsequent elevation of pro-inflammatory cytokine, TNF-α, protein expression of iNOS and myeloperoxidase activities. Furthermore, fisetin markedly attenuated the translocation of cytochrome c protein from the mitochondria to the cytosol; decreased the expression of pro-apoptotic proteins including Bax, cleaved caspase-3, cleaved caspase-9 and p53; and prevented the decline of anti-apoptotic protein, Bcl-2. The cisplatin-induced mRNA expression of NOX2/gp91phox and NOX4/RENOX and the NADPH oxidase enzyme activity were also significantly lowered by fisetin treatment. Moreover, the evaluated mitochondrial respiratory enzyme activities and mitochondrial antioxidants were restored by fisetin treatment. Estimation of platinum concentration in kidney tissues revealed that fisetin treatment along with cisplatin did not alter the cisplatin uptake in kidney tissues. In conclusion, these findings suggest that fisetin may be used as a promising adjunct candidate for cisplatin use.

  4. Carbon monoxide-bound hemoglobin vesicles ameliorate multiorgan injuries induced by severe acute pancreatitis in mice by their anti-inflammatory and antioxidant properties.

    Science.gov (United States)

    Nagao, Saori; Taguchi, Kazuaki; Sakai, Hiromi; Yamasaki, Keishi; Watanabe, Hiroshi; Otagiri, Masaki; Maruyama, Toru

    Carbon monoxide (CO) has attracted attention as a possible therapeutic agent for affecting anti-inflammatory and antioxidant activities. Previously, CO-bound hemoglobin vesicle (CO-HbV) was developed as a nanotechnology-based CO donor, and its safety profile and therapeutic potential as a clinically applicable carrier of CO were examined in vitro and in vivo. In the present study, the therapeutic efficacy of CO-HbV against severe acute pancreatitis was examined with secondary distal organ-injured model mice that were fed with a choline-deficient ethionine-supplemented diet. A CO-HbV treatment significantly reduced the mortality of the acute pancreatitis model mice compared to saline and HbV. Biochemical and histological evaluations clearly showed that CO-HbV suppressed acute pancreatitis by inhibiting the production of systemic proinflammatory cytokines, neutrophil infiltration, and oxidative injuries in pancreatic tissue. Interestingly, CO-HbV also diminished the subsequent damage to distal organs including liver, kidneys, and lungs. This could be due to the suppression of neutrophil infiltration into tissues and the subsequently enhanced oxidative injuries. In contrast, O 2 -bound HbV, the inactive form of CO-HbV, was ineffective against both pancreatitis and distal organ injuries, confirming that CO was directly responsible for the protective effects of CO-HbV in acute pancreatitis. These findings suggest that CO-HbV has anti-inflammatory and antioxidant characteristics of CO and consequently exerts a superior protective effect against acute pancreatitis-induced multiorgan damage.

  5. Ameliorative Effect of Fisetin on Cisplatin-Induced Nephrotoxicity in Rats via Modulation of NF-κB Activation and Antioxidant Defence

    Science.gov (United States)

    Sahu, Bidya Dhar; Kalvala, Anil Kumar; Koneru, Meghana; Mahesh Kumar, Jerald; Kuncha, Madhusudana; Rachamalla, Shyam Sunder; Sistla, Ramakrishna

    2014-01-01

    Nephrotoxicity is a dose-dependent side effect of cisplatin limiting its clinical usage in the field of cancer chemotherapy. Fisetin is a bioactive flavonoid with recognized antioxidant and anti-inflammatory properties. In the present study, we investigated the potential renoprotective effect and underlying mechanism of fisetin using rat model of cisplatin-induced nephrotoxicity. The elevation in serum biomarkers of renal damage (blood urea nitrogen and creatinine); degree of histopathological alterations and oxidative stress were significantly restored towards normal in fisetin treated, cisplatin challenged animals. Fisetin treatment also significantly attenuated the cisplatin-induced IκBα degradation and phosphorylation and blocked the NF-κB (p65) nuclear translocation, with subsequent elevation of pro-inflammatory cytokine, TNF-α, protein expression of iNOS and myeloperoxidase activities. Furthermore, fisetin markedly attenuated the translocation of cytochrome c protein from the mitochondria to the cytosol; decreased the expression of pro-apoptotic proteins including Bax, cleaved caspase-3, cleaved caspase-9 and p53; and prevented the decline of anti-apoptotic protein, Bcl-2. The cisplatin-induced mRNA expression of NOX2/gp91phox and NOX4/RENOX and the NADPH oxidase enzyme activity were also significantly lowered by fisetin treatment. Moreover, the evaluated mitochondrial respiratory enzyme activities and mitochondrial antioxidants were restored by fisetin treatment. Estimation of platinum concentration in kidney tissues revealed that fisetin treatment along with cisplatin did not alter the cisplatin uptake in kidney tissues. In conclusion, these findings suggest that fisetin may be used as a promising adjunct candidate for cisplatin use. PMID:25184746

  6. Anti-pulmonary fibrotic activity of salvianolic acid B was screened by a novel method based on the cyto-biophysical properties.

    Science.gov (United States)

    Liu, Miao; Zheng, Mingjing; Xu, Hanying; Liu, Lianqing; Li, Yanchun; Xiao, Wei; Li, Jianchun; Ma, Enlong

    Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-β1 (TGF-β1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-β1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control. Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-β1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-β1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Ameliorative effect of ethanolic extract of leaves of Momordica ...

    African Journals Online (AJOL)

    Mormodica charantia has been shown to possess antioxidant, hepatoprotective and anticancer effects while the kidneys have been shown to be the second largest repository of lead in lead poisoining. This study assessed the ameliorative effect of ethanolic leaf extract of Momordica charantia on lead nitrate induced kidney ...

  8. Ameliorative effects of α-lipoic acid on high-fat diet-induced oxidative stress and glucose uptake impairment of T cells.

    Science.gov (United States)

    Cui, Jue; Huang, Dejian; Zheng, Yi

    2016-10-01

    The incidence of obesity and metabolic disease continues to rise, mainly associated with consumption of a high-fat diet (HFD). Previous studies have indicated that HFD could disturb the immune system, leading to immunodeficiency and inflammation. Several mechanisms have been postulated to account for immunodeficiency associated with HFD, one being oxidative stress. To further investigate the effects of HFD on glucose metabolism and proliferative capability of T cells and the protective effects of α-lipoic acid (LA), male C57BL/6J mice were fed a normal chow (10% fat), an HFD (60% fat), an LA supplement (HFD +0.1%LA), and a N-acetyl-L-cysteine supplement (HFD +0.1% NAC) for 10 weeks. Results showed that 10-week HFD increased intracellular reactive oxygen species (ROS) production, induced oxidative stress state formation, inhibited glucose uptake, decreased ATP concentration, reduced proliferative rate, and dampened IL-2 production of T cells of mice. Administration of LA significantly alleviated these changes induced by HFD. These findings reveal that oxidative stress of T cells caused by HFD may be a key factor leading to glucose metabolism reduction and proliferative capability and function impairment of T cells. LA, as a potent agonist, could promote Nrf2 nuclear translocation and up-regulate expression of Nrf2 target genes (Ho-1 and Prdx1), which can eliminate excess ROS and restore redox balance of cells.

  9. Antioxidant Mechanism of Rutin on Hypoxia-Induced Pulmonary Arterial Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Qian Li

    2014-11-01

    Full Text Available Reactive oxygen species (ROS are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study, we proposed that rutin attenuated hypoxia-induced pulmonary artery smooth muscle cell (PASMC proliferation by scavenging ROS. Immunofluorescence data showed that rutin decreased the production of ROS, which was mainly generated through mitochondria and NADPH oxidase 4 (Nox4 in pulmonary artery endothelial cells (PAECs. Western blot results provided further evidence on rutin increasing expression of Nox4 and hypoxia-inducible factor-1α (HIF-1α. Moreover, cell cycle analysis by flow cytometry indicated that proliferation of PASMCs triggered by hypoxia was also repressed by rutin. However, N-acetyl-L-cysteine (NAC, a scavenger of ROS, abolished or diminished the capability of rutin in repressing hypoxia-induced cell proliferation. These data suggest that rutin shows a potential benefit against the development of hypoxic pulmonary arterial hypertension by inhibiting ROS, subsequently preventing hypoxia-induced PASMC proliferation.

  10. Antioxidant mechanism of Rutin on hypoxia-induced pulmonary arterial cell proliferation.

    Science.gov (United States)

    Li, Qian; Qiu, Yanli; Mao, Min; Lv, Jinying; Zhang, Lixin; Li, Shuzhen; Li, Xia; Zheng, Xiaodong

    2014-11-18

    Reactive oxygen species (ROS) are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study, we proposed that rutin attenuated hypoxia-induced pulmonary artery smooth muscle cell (PASMC) proliferation by scavenging ROS. Immunofluorescence data showed that rutin decreased the production of ROS, which was mainly generated through mitochondria and NADPH oxidase 4 (Nox4) in pulmonary artery endothelial cells (PAECs). Western blot results provided further evidence on rutin increasing expression of Nox4 and hypoxia-inducible factor-1α (HIF-1α). Moreover, cell cycle analysis by flow cytometry indicated that proliferation of PASMCs triggered by hypoxia was also repressed by rutin. However, N-acetyl-L-cysteine (NAC), a scavenger of ROS, abolished or diminished the capability of rutin in repressing hypoxia-induced cell proliferation. These data suggest that rutin shows a potential benefit against the development of hypoxic pulmonary arterial hypertension by inhibiting ROS, subsequently preventing hypoxia-induced PASMC proliferation.

  11. Copper exposure induces toxicity to the antioxidant system via the destruction of Nrf2/ARE signaling and caspase-3-regulated DNA damage in fish muscle: Amelioration by myo-inositol

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Wei-Dan; Liu, Yang [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Jiang, Jun [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Wu, Pei [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Feng, Lin, E-mail: fenglin@sicau.edu.cn [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Zhou, Xiao-Qiu, E-mail: zhouxq@sicau.edu.cn [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China)

    2015-02-15

    Highlights: • Cu stress decreased fish muscle CuZnSOD, GPx1a, GPx1b and PKCδ mRNA levels. • Cu stress caused fish muscle lower nuclear Nrf2 levels and poor ARE binding ability. • Cu stress induced caspase-3 signaling-modulated DNA fragmentation in fish muscle. • Pre-treatment with MI prevented fish muscle from Cu-induced oxidative damages. - Abstract: The muscle is the main portion of fish that is consumed by humans. Copper (Cu) can induce oxidative damage in fish muscle. However, the effects of Cu exposure on the muscle antioxidant system and molecular patterns and preventive measures against these effects remain unclear. In this study, ROS production, enzymatic and mRNA levels of antioxidant enzymes and NF-E2-related factor 2 (Nrf2) signaling-related molecules, antioxidant response element (ARE) binding ability, DNA fragmentation and caspase-3 activities were analyzed in fish muscle following Cu exposure or myo-inositol (MI) pre-administration. The results indicated that contamination due to copper exposure caused an approximately three-fold increase in ROS production, induced lipid peroxidation and protein oxidation, and resulted in depletion of the glutathione (GSH) content of fish muscle. Moreover, Cu exposure caused decreases in the activities of total superoxide dismutase (T-SOD), CuZnSOD, and glutathione peroxidase (GPx) that were accompanied by decreases in CuZnSOD, GPx1a, GPx1b and signaling factor protein kinase C delta mRNA levels. The decreases in the antioxidant enzyme gene mRNA levels were confirmed to be partly due to the reduced nuclear Nrf2 protein levels, poor ARE binding ability and increased caspase-3 signaling-modulated DNA fragmentation in the fish muscle. Interestingly, MI pre-treatment prevented fish muscle from Cu-induced oxidative damages mainly through increasing the GSH content, and increasing the CuZnSOD and GPx activities and corresponding mRNA levels and ARE binding ability. Taken together, our results show for the first

  12. Copper exposure induces toxicity to the antioxidant system via the destruction of Nrf2/ARE signaling and caspase-3-regulated DNA damage in fish muscle: Amelioration by myo-inositol

    International Nuclear Information System (INIS)

    Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Feng, Lin; Zhou, Xiao-Qiu

    2015-01-01

    Highlights: • Cu stress decreased fish muscle CuZnSOD, GPx1a, GPx1b and PKCδ mRNA levels. • Cu stress caused fish muscle lower nuclear Nrf2 levels and poor ARE binding ability. • Cu stress induced caspase-3 signaling-modulated DNA fragmentation in fish muscle. • Pre-treatment with MI prevented fish muscle from Cu-induced oxidative damages. - Abstract: The muscle is the main portion of fish that is consumed by humans. Copper (Cu) can induce oxidative damage in fish muscle. However, the effects of Cu exposure on the muscle antioxidant system and molecular patterns and preventive measures against these effects remain unclear. In this study, ROS production, enzymatic and mRNA levels of antioxidant enzymes and NF-E2-related factor 2 (Nrf2) signaling-related molecules, antioxidant response element (ARE) binding ability, DNA fragmentation and caspase-3 activities were analyzed in fish muscle following Cu exposure or myo-inositol (MI) pre-administration. The results indicated that contamination due to copper exposure caused an approximately three-fold increase in ROS production, induced lipid peroxidation and protein oxidation, and resulted in depletion of the glutathione (GSH) content of fish muscle. Moreover, Cu exposure caused decreases in the activities of total superoxide dismutase (T-SOD), CuZnSOD, and glutathione peroxidase (GPx) that were accompanied by decreases in CuZnSOD, GPx1a, GPx1b and signaling factor protein kinase C delta mRNA levels. The decreases in the antioxidant enzyme gene mRNA levels were confirmed to be partly due to the reduced nuclear Nrf2 protein levels, poor ARE binding ability and increased caspase-3 signaling-modulated DNA fragmentation in the fish muscle. Interestingly, MI pre-treatment prevented fish muscle from Cu-induced oxidative damages mainly through increasing the GSH content, and increasing the CuZnSOD and GPx activities and corresponding mRNA levels and ARE binding ability. Taken together, our results show for the first

  13. Anti-pulmonary fibrotic activity of salvianolic acid B was screened by a novel method based on the cyto-biophysical properties

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Miao; Zheng, Mingjing; Xu, Hanying [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Liu, Lianqing [Shenyang Institute of Automation China Academy of Sciences, Shenyang, 110016 (China); Li, Yanchun [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Xiao, Wei [Jiangsu Kanion Pharmaceutical Co., Ltd., Nanjing, 222001 (China); Li, Jianchun, E-mail: lijianchun0317@sina.com.cn [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Ma, Enlong, E-mail: enlong_ma2014@hotmail.com [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Jiangsu Kanion Pharmaceutical Co., Ltd., Nanjing, 222001 (China)

    2015-12-04

    Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-β1 (TGF-β1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-β1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control. Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-β1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-β1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening. - Highlights: • Fibrogenesis was accompanied with the changes of cyto-biophysical properties. • Cyto-biophysical properties could be markers for anti-fibrotic drugs screening. • Stiffness is a leading index among all biophysical markers. • SalB was

  14. Anti-pulmonary fibrotic activity of salvianolic acid B was screened by a novel method based on the cyto-biophysical properties

    International Nuclear Information System (INIS)

    Liu, Miao; Zheng, Mingjing; Xu, Hanying; Liu, Lianqing; Li, Yanchun; Xiao, Wei; Li, Jianchun; Ma, Enlong

    2015-01-01

    Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-β1 (TGF-β1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-β1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control. Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-β1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-β1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening. - Highlights: • Fibrogenesis was accompanied with the changes of cyto-biophysical properties. • Cyto-biophysical properties could be markers for anti-fibrotic drugs screening. • Stiffness is a leading index among all biophysical markers. • SalB was

  15. The status of antioxidant defences in Glucose-6-phosphate ...

    African Journals Online (AJOL)

    The aim of this study was to clarify the role of G6PD in cellular antioxidant defense; the level of glutathione, catalase, NADPH and estimate the level of malondialdehyde which reflect the oxidative stress across the cell membrane. Also to study the effect of antioxidant treatment (vitamins C and E) to ameliorate high sensitivity ...

  16. Antioxidative effects of cerium dioxide nanoparticles ameliorate age-related male infertility: optimistic results in rats and the review of clinical clues for integrative concept of men health and fertility.

    Science.gov (United States)

    Kobyliak, Nazarii M; Falalyeyeva, Tetyana M; Kuryk, Olena G; Beregova, Tetyana V; Bodnar, Petro M; Zholobak, Nadiya M; Shcherbakov, Oleksandr B; Bubnov, Rostyslav V; Spivak, Mykola Ya

    2015-01-01

    Male infertility has largely idiopathic, multifactorial origin. Oxidative stress is a major factor that affects spermatogenesis, in particular in aging. Cerium dioxide nanoparticles (CNPs) due to their antioxidative properties are promising to impact on the development of male infertility. The aims of this study were to investigate the effects of CNPs on fertility parameters in 24-month male rats and to overview relevant literature in the field of personalized treatments, predictive diagnosis, and preventive measures for male health and fertility. We included 30 24-month-old male rats. After a week of adaptation to the standard diet, the rats were randomly divided into three groups with ten rats in each. Group 1 (controls) received only a standard diet. The rats of group 2 and 3 in adjunct to the standard diet during 10 days received intragastrically 10 % sodium citrate and citrate-coated CNPs in dose 1 mg/kg, respectively. We assessed sex hormones, epididymal sperm parameters and spermatogenesis, ultrasound, and morphological data of rat reproductive organs. After a 10-day administration of CNPs, we revealed significant decrease of lipid peroxidation product levels in serum and increase of catalase and SOD activity, associated with increase of sperm count (p age-related decrease of activated Leydig cell number and focal atrophy of the seminiferous tubules. In CNP group, we observed regeneration of seminiferous tubules, increase number and activation of Leydig cells, and 2.5-fold significant increase of serum testosterone. Ultrasound data showed the slight increase of linear measurement and volume of rat testes in CNP group. Review highlights the benefits for predictive diagnosis, preventive measures, and personalized approaches to manage male infertility in the general concept of male health also related to aging. Citrate-coated 2-5-nm CNPs lead to increase in sex hormones levels, sperm count, and quality, as well as the activation of spermatogenesis in 24-month

  17. Naringin inhibits ROS-activated MAPK pathway in high glucose-induced injuries in H9c2 cardiac cells.

    Science.gov (United States)

    Chen, Jingfu; Guo, Runmin; Yan, Hai; Tian, Lihong; You, Qiong; Li, Shanghai; Huang, Ruina; Wu, Keng

    2014-04-01

    Naringin, an active flavonoid isolated from citrus fruit extracts, exhibits biological and pharmacological properties, such as antioxidant activity and antidiabetic effect. Mitogen-activated protein kinase (MAPK) signalling pathway has been shown to participate in hyperglycaemia-induced injury. The present study tested the hypothesis that naringin protects against high glucose (HG)-induced injuries by inhibiting MAPK pathway in H9c2 cardiac cells. To examine this, the cells were treated with 35 mM glucose (HG) for 24 hr to establish a HG-induced cardiomyocyte injury model. The cells were pre-treated with 80 μM naringin for 2 hr before exposure to HG. The findings of this study showed that exposure of H9c2 cells to HG for 24 hr markedly induced injuries, as evidenced by a decrease in cell viability, increases in apoptotic cells and reactive oxygen species (ROS) production, as well as dissipation of mitochondrial membrance potential (MMP). These injuries were significantly attenuated by the pre-treatment of cells with either naringin or SB203580 (a selective inhibitor of p38 MAPK) or U0126 (a selective inhibitor of extracellular signal regulated kinase 1/2, ERK1/2) or SP600125 (a selective inhibitor of c-jun N-termanal kinase, JNK) before exposure to HG, respectively. Furthermore, exposure of cells to HG increased the phosphorylation of p38 MAPK, ERK1/2 and JNK. The increased activation of MAPK pathway was ameliorated by pre-treatment with either naringin or N-acetyl-L-cysteine (NAC), a ROS scavenger, which also reduced HG-induced cytotoxicity and apoptosis, leading to increase in cell viability and decrease in apoptotic cells. In conclusion, our findings provide new evidence for the first time that naringin protects against HG-induced injuries by inhibiting the activation of MAPK (p38 MAPK, ERK1/2 and JNK) and oxidative stress in H9c2 cells. © 2013 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  18. Administration of red ginseng ameliorates memory decline in aged mice.

    Science.gov (United States)

    Lee, Yeonju; Oh, Seikwan

    2015-07-01

    It has been known that ginseng can be applied as a potential nutraceutical for memory impairment; however, experiments with animals of old age are few. To determine the memory enhancing effect of red ginseng, C57BL/6 mice (21 mo old) were given experimental diet pellets containing 0.12% red ginseng extract (approximately 200 mg/kg/d) for 3 mo. Young and old mice (4 mo and 21 mo old, respectively) were used as the control group. The effect of red ginseng, which ameliorated memory impairment in aged mice, was quantified using Y-maze test, novel objective test, and Morris water maze. Red ginseng ameliorated age-related declines in learning and memory in older mice. In addition, red ginseng's effect on the induction of inducible nitric oxide synthase and proinflammatory cytokines was investigated in the hippocampus of aged mice. Red ginseng treatment suppressed the production of age-processed inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, and interleukin-1β expressions. Moreover, it was observed that red ginseng had an antioxidative effect on aged mice. The suppressed glutathione level in aged mice was restored with red ginseng treatment. The antioxidative-related enzymes Nrf2 and HO-1 were increased with red ginseng treatment. The results revealed that when red ginseng is administered over long periods, age-related decline of learning and memory is ameliorated through anti-inflammatory activity.

  19. Amelioration of altered antioxidant status and membrane linked ...

    Indian Academy of Sciences (India)

    Unknown

    membrane fluidity have been implicated in disease process and diabetic complications (Hong et al 2004). ... decreased fluid and food intake and loss in body weight. (Brichard et al 1988; Domingo et al 1991). ...... lesterolaemic effect of fenugreek seeds in dogs; Atheroscle- rosis 50 105–111. Vizi E S and Oberfrank F 1992 ...

  20. Amelioration of altered antioxidant status and membrane linked ...

    Indian Academy of Sciences (India)

    Unknown

    ) have been reported to have antidiabetic effects. However, SOV exerts hypoglycemic effects at relatively high doses with several toxic ef- fects. We used low doses of vanadate in combination with TSP and evaluated their antidiabetic effects ...

  1. Chronic antioxidant therapy fails to ameliorate hypertension: potential mechanisms behind

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, Olga; Šimko, F.

    2009-01-01

    Roč. 27, Suppl.6 (2009), S32-S36 ISSN 0263-6352 R&D Projects: GA ČR(CZ) GA305/08/0139 Institutional research plan: CEZ:AV0Z50110509 Keywords : endothelial dysfunction * NADP(H) oxidase * reactive oxygen species Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.988, year: 2009

  2. Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice.

    Science.gov (United States)

    Liu, Ting Ting; Zeng, Yi; Tang, Kun; Chen, XueMeng; Zhang, Wei; Xu, Xiao Le

    2017-07-01

    Dihydromyricetin, the most abundant flavonoid in Ampelopsis grossedentata, exerts numerous pharmacological activities, including anti-inflammatory, antioxidant, hepatoprotective, and lipid regulatory activities; however, its protective effect against atherosclerosis remains poorly understood. The aim of the present study was to evaluate the effects of dihydromyricetin on high fat diet (HFD)-induced atherosclerosis using LDL receptor deficient (LDLr -/- ) mice. Blood samples were collected for determination of serum lipid profiles, oxidized LDL (ox-LDL) and pro-inflammatory cytokines. Histology, hepatic lipid content, quantification of atherosclerosis, assessment of oxidative stress and inflammation were performed on liver and aorta samples by molecular biology methods. The effects of dihydromyricetin on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) dysfunction and foam cell formation were further studied. (1) Dihydromyricetin ameliorated hyperlipidemia, reduced serum ox-LDL, IL-6 and TNF-α levels in HFD-fed LDLr -/- mice. Moreover, (2) dihydromyricetin suppressed hepatic lipid accumulation and increased protein expressions of PPARα, LXRα and ABCA1. (3) It inhibited atherosclerotic lesion formation and favoured features of plaque stability. (4) Dihydromyricetin prevented hepatic and aortic inflammation as evidenced by the reduced IL-6 and TNF-α mRNA expression; (5) it prevented hepatic and aortic oxidative stress by normalizing activities of antioxidant enzymes in the liver and suppressing reactive oxygen species generation and NOX2 protein expression in both liver and aorta; (6) it inhibited oxLDL-induced injury, monocytes adhesion and oxidative stress in HUVECs and (7) inhibited macrophage foam cell formation and enhanced cholesterol efflux. These findings suggest that dihydromyricetin could reduce atherosclerosis via its pleiotropic effects, including improvement of endothelial dysfunction, inhibition of macrophage foam cell formation

  3. Quercetin and omega 3 ameliorate oxidative stress induced by aluminium chloride in the brain.

    Science.gov (United States)

    Ali, Haytham Abdallah; Afifi, Mohamed; Abdelazim, Aaser Mohamed; Mosleh, Yahia Youssef

    2014-08-01

    Exposure to high levels of aluminum (Al) leads to neurodegeneration, which may be mediated through over-generation of free radicals. So, in the present study, we investigated the ability of both quercetin and omega 3 to ameliorate adverse effects of Al on brain antioxidants by monitoring the main brain antioxidant enzymes on molecular and cellular levels. The obtained results indicated that Al induced oxidative stress through induction of free radical production and inhibition of activity and expression of the antioxidant enzymes catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx); and at the same time induced superoxide dismutase (SOD) activity and gene expression. Both quercetin (QE) and omega 3 have the ability to overcome Al-induced oxidative stress, manifested by the significant reduction in free radical concentration and induction of the activity and gene expression of the brain antioxidant enzymes.

  4. Hypolipidemic and Antioxidant Activity of Camel Milk on Poloxamer ...

    African Journals Online (AJOL)

    The aim of this study is to investigate the ameliorative and antioxidant effect of camel milk on poloxamer 407 (P407) induced hyperlipidemia in albino rats. Methods: Thirty male wistar rats were subdivided into six groups (Group 1-6) with each containing five animals (n=5). Group 1 served as normal control, while Groups 2-6 ...

  5. Modulatory Role of Antioxidant Vitamins C and E on Erythrocyte ...

    African Journals Online (AJOL)

    Vitamin C and E supplements were administered to sodium nitrate-treated rats in order to examine the possible ameliorative effects of these antioxidants on erythrocyte osmotic fragility. Seventy adult Wistar rats were randomly divided into seven groups (n=10) and administered drugs or distilled water orally using a metallic ...

  6. Deltamethrin Induced Alteration of Biochemical Parameters in Channa punctata, Bloch and its Amelioration by Quercetin.

    Science.gov (United States)

    Bhattacharjee, Parmita; Das, Suchismita

    2017-06-01

    We tested the impacts of pyrethroid pesticide deltamethrin and its amelioration by a flavonoid, quercetin, using tissue macromolecules (protein, amino acid, carbohydrate and glycogen) and antioxidant enzymes (superoxide dismutase, catalase and peroxidase) as biomarkers, on fish, Channa punctata, gill and liver. Our study proved that quercetin supplement alone, in the absence of pesticide, might be detrimental to fish health, in terms of depletion of major tissue macromolecules, but, such supplement may be beneficial to fish with pesticide associated oxidative stress. Multivariate analyses predicted that the antioxidant enzymes and lipid peroxidation were closely associated biomarkers; whereas tissue macromolecules formed a different cluster. Hence, oxidative stress biomarkers in fish can be considered a valuable tool in assessment of deltamethrin stress and its amelioration by quercetin. The work can pave the way for further research in establishing quercetin as a probable curative agent.

  7. Levetiracetam ameliorates ovarian function in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Akman, Levent; Erbas, Oytun; Akdemir, Ali; Yavasoglu, Altug; Taskiran, Dilek; Kazandi, Mert

    2015-01-01

    Diabetes mellitus can adversely affect gonadal function. In the present study, we aimed to investigate the protective effects and mechanism of action of levetiracetam (LEV) on the ovaries in a streptozotocin (STZ)-induced diabetes model in rats. Twenty-one adult female rats were assigned to three groups as control, diabetes group treated with 1 mL/kg/d saline (STZ + SP) and diabetes group treated with 600 mg/kg/d LEV (STZ + LEV). Following 4 weeks treatment, blood samples were collected for biochemical analysis and ovariectomy was performed for histopathological examination. Plasma anti-Mullerian hormone (AMH), glutathione and total anti-oxidant capacity values were significantly lower whereas lipid peroxides and transforming growth factor-β (TGF-β) values were significantly higher in STZ + SP group compared to control. LEV treatment successfully decreased lipid peroxidation and TGF-β levels, and also increased anti-oxidant parameters and AMH levels in diabetic rats. Saline-treated rats significantly displayed ovarian degeneration and decreased counts of follicles. However, treatment of diabetic rats with LEV effectively prevented the degenerative changes and follicle loss. Also, LEV suppressed ovarian nuclear factor-kappa B (NF-kB) immunoexpression in diabetic rats. Taken together, we propose that LEV can ameliorate the adverse effects of diabetes on ovarian function via decreasing NF-kB expression and oxidative stress and increasing anti-oxidant status in rats.

  8. Black ginseng extract ameliorates hypercholesterolemia in rats.

    Science.gov (United States)

    Saba, Evelyn; Jeon, Bo Ra; Jeong, Da-Hye; Lee, Kija; Goo, Youn-Kyoung; Kim, Seung-Hyung; Sung, Chang-Keun; Roh, Seong-Soo; Kim, Sung Dae; Kim, Hyun-Kyoung; Rhee, Man-Hee

    2016-04-01

    Ginseng (Panax ginseng Meyer) is a well-characterized medicinal herb listed in the classic oriental herbal dictionary as "Shin-nong-bon-cho-kyung." Ginseng has diverse pharmacologic and therapeutic properties. Black ginseng (BG, Ginseng Radix nigra) is produced by repeatedly steaming fresh ginseng nine times. Studies of BG have shown that prolonged heat treatment enhances the antioxidant activity with increased radical scavenging activity. Several recent studies have showed the effects of BG on increased lipid profiles in mice. In this study report the effects of water and ethanol extracts of BG on hypercholesterolemia in rats. To our knowledge, this is the first time such an effect has been reported. Experiments were conducted on male Sprague Dawley rats fed with a high-cholesterol diet supplemented with the water and ethanol extracts of BG (200 mg/kg). Their blood cholesterol levels, serum white blood cell levels, and cholesterol-metabolizing marker genes messenger RNA (mRNA) expression were determined. Liver and adipose tissues were histologically analyzed. We found that BG extracts efficiently reduced the total serum cholesterol levels, low-density lipoprotein (LDL) levels with increased food efficiency ratio and increased number of neutrophil cells. It also attenuated the key genes responsible for lipogenesis, that is, acetyl-coenzyme A (CoA) acetyltransferase 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and sterol regulatory element-binding protein 2, at the mRNA level inside liver cells. Furthermore, the BG extract also reduced the accumulation of fat in adipose tissues, and inhibited the neutral fat content in liver cells stained with hematoxylin and eosin and oil red O. Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  9. Quercetin Treatment Ameliorates Systemic Oxidative Stress in Cirrhotic Rats

    Science.gov (United States)

    Vieira, Emanuelle Kerber; Bona, Silvia; Di Naso, Fábio Cangeri; Porawski, Marilene; Tieppo, Juliana; Marroni, Norma Possa

    2011-01-01

    Our aim was to investigate whether the antioxidant quercetin protects against liver injury and ameliorates the systemic oxidative stress in rats with common bile duct ligation. Secondary biliary cirrhosis was induced through 28 days of bile duct obstruction. Animals received quercetin (Q) after 14 days of obstruction. Groups of control (CO) and cirrhotic (CBDL) animals received a daily 50 mg/kg body weight i.p. injection of quercetin (CO + Q; CBDL + Q) or vehicle (CO; CBDL). Quercetin corrected the reduction in superoxide dismutase (SOD), catalase CAT, and glutathione peroxidase GPx activities and prevented the increase of thiobarbituric acid reactive substances (TBARS), aminotransferases, and alkaline phosphatase in cirrhotic animals. Quercetin administration also corrected the reduced total nitrate concentration in the liver and prevented liver fibrosis and necrosis. These effects suggest that quercetin might be a useful agent to preserve liver function and prevent systemic oxidative stress. PMID:21991520

  10. Antioxidative defense

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2011-01-01

    Full Text Available Free radicals occur constantly during metabolism and take part in numerous physiological processes, such as: intra-cellular and inter-cellular signalization, gene expression, removal of damaged or senescent cells, and control of the tone of blood vessels. However, there is an increased quantity of free radicals in situations of so-called oxidative stress, when they cause serious damage to cellular membranes (peroxidation of their lipids, damage of membrane proteins, and similar, to interior cellular protein molecules, as well as DNA molecules and carbohydrates. This is precisely why the organism has developed numerous mechanisms for removing free radicals and/or preventing their production. Some of these are enzyme-related and include superoxide-dismutase, catalase, glutathione-peroxidase, and others. Other, non-enzyme mechanisms, imply antioxidative activities of vitamins E and C, provitamin A, coenzyme Q, reduced glutation, and others. Since free radicals can leave the cell that has produced them and become dispersed throughout the body, in addition to antioxidative defense that functions within cellular structures, antioxidant extra-cellular defense has also been developed. This is comprised by: transferrin, lactoferrin, haptoglobin, hemopexin, ceruloplasmin, albumins, extra-cellular isoform SOD, extracellular glutathione-peroxidase, glucose, bilirubin, urates, and many other molecules.

  11. Black ginseng extract ameliorates hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Evelyn Saba

    2016-04-01

    Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  12. Antioxidants: Protecting Healthy Cells

    Science.gov (United States)

    ... and Nutrients Antioxidants - Protecting Healthy Cells Print Email Antioxidants - Protecting Healthy Cells Reviewed by Taylor Wolfram, MS, ... to cardiovascular disease and certain types of cancers. Antioxidants — such as vitamins C and E and carotenoids, ...

  13. Antioxidants and antioxidant capacity of human milk

    OpenAIRE

    Živković, Jelena; Sunarić, Slavica; Trutić, Nataša; Denić, Marko; Kocić, Gordana; Jovanović, Tatjana

    2015-01-01

    Milk contains plenty of enzymatic and non-enzymatic antioxidant components that probably account for the vital antioxidant protection of the infants at early stages of life against the development of complications induced by oxygen free radicals. Indigenous milk enzymes play a key role in regulating lactogenesis, including active involution of mammary gland. Moreover, they are essential constituents of antioxidation and the innate immune system of milk. Among antioxidant enzymes, superoxide d...

  14. Fucoidan Extracts Ameliorate Acute Colitis.

    Directory of Open Access Journals (Sweden)

    Qi Ying Lean

    Full Text Available Inflammatory bowel diseases (IBD, such as ulcerative colitis and Crohn's disease, are an important cause of morbidity and impact significantly on quality of life. Overall, current treatments do not sustain a long-term clinical remission and are associated with adverse effects, which highlight the need for new treatment options. Fucoidans are complex sulphated, fucose-rich polysaccharides, found in edible brown algae and are described as having multiple bioactivities including potent anti-inflammatory effects. Therefore, the therapeutic potential of two different fucoidan preparations, fucoidan-polyphenol complex (Maritech Synergy and depyrogenated fucoidan (DPF was evaluated in the dextran sulphate sodium (DSS mouse model of acute colitis. Mice were treated once daily over 7 days with fucoidans via oral (Synergy or DPF or intraperitoneal administration (DPF. Signs and severity of colitis were monitored daily before colons and spleens were collected for macroscopic evaluation, cytokine measurements and histology. Orally administered Synergy and DPF, but not intraperitoneal DPF treatment, significantly ameliorated symptoms of colitis based on retention of body weight, as well as reduced diarrhoea and faecal blood loss, compared to the untreated colitis group. Colon and spleen weight in mice treated with oral fucoidan was also significantly lower, indicating reduced inflammation and oedema. Histological examination of untreated colitis mice confirmed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and oedema, while all aspects of this pathology were alleviated by oral fucoidan. Importantly, in this model, the macroscopic changes induced by oral fucoidan correlated significantly with substantially decreased production of at least 15 pro-inflammatory cytokines by the colon tissue. Overall, oral fucoidan preparations significantly reduce the inflammatory pathology associated with DSS-induced colitis and could

  15. Role of Oxidative Stress in the Pathogenesis of Pancreatitis: Effect of Antioxidant Therapy

    OpenAIRE

    Robles, Lourdes; Vaziri, Nosratola D; Ichii, Hirohito

    2013-01-01

    Oxidative stress plays an important role in the pathogenesis of acute pancreatitis. The exact pathogenesis of pancreatitis remains unknown but several mechanisms related to oxidative and inflammatory stress are implicated. It is reasonable to surmise that antioxidants would play a protective role in ameliorating the deleterious effects of pancreatitis. We have a wealth of data from animal models that reveal a positive correlation between antioxidant drugs and improved outcomes in experimental...

  16. Ameliorative effect of tamarind leaf on fluoride-induced metabolic alterations.

    Science.gov (United States)

    Vasant, Rupal A; Narasimhacharya, A V R L

    2012-11-01

    Fluoride is a serious health hazard across several nations, and chronic intake of fluoride deranges the carbohydrate, lipid and antioxidant metabolism in general. As there are limited remedial measures to prevent fluorosis, we investigated the role of tamarind leaf as a food supplement in restoration of carbohydrate, lipid and antioxidant metabolism in fluoride-exposed albino rats. Albino rats were exposed to fluoride (100 ppm sodium fluoride) through drinking water and fed diet supplemented with tamarind leaf powder (2.5, 5 and 10 g %) for 4 weeks. Carbohydrate, lipid and antioxidant profiles were investigated in both controls and fluoride-exposed animals. While 4-week exposure to fluoride elevated plasma glucose and lipid profiles, simulating diabetic and hyperlipidaemic conditions, the antioxidant defence mechanisms of fluoride-exposed rats were compromised, with elevation and decline in lipid peroxidation and high-density lipoprotein (HDL)-cholesterol, respectively. When the diet was supplemented with tender tamarind leaves (used in southern India as a replacement for tamarind or other sour food ingredients), significant improvements in carbohydrate and lipid profiles occurred as evidenced by decreased plasma glucose and lipid levels, lipid peroxidation, increased hepatic glycogen content, hexokinase activity and cholesterol excretion, with simultaneous improvement in antioxidant profiles of both hepatic and renal tissues. These findings are significant in view of the need for cost-effective approaches to tackle fluorosis as an environmental hazard and use of food supplements as ameliorative measures.

  17. Silymarin and Nigella sativa extract ameliorate paracetamol induced oxidative stress and renal dysfunction in male mice

    Directory of Open Access Journals (Sweden)

    Reham Zakaria Hamza

    2015-06-01

    Full Text Available Objective: To evaluate the ameliorative role of silymarin or/and Nigella sativa (N. sativa water extract against N-acetyl-p-aminophenol (APAP-induced renal function deterioration in male mice at the biochemical levels. Methods: The mice were divided into seven groups (10/group. The first group was served as control. The second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa water extract alone, respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa water extract, respectively. The seventh group was treated with a combination of both ameliorative compounds (silymarin and N. sativa water extract with APAP and all animals were treated for a period of 30 days. Results: Exposure to APAP at the treated dose for mice led to an alteration of kidney function parameters, increase in the level of serum urea and creatinine. Also, paracetamol administration induced oxidative stress in kidney homogenates by increasing malondialdhyde level and decreasing superoxide dismutase and catalase activities and this stress was ameliorated by administration of either silymarin or N. sativa water extract. Conclusions: Administration of silymarin or/and N. sativa water extract to APAP-treated mice alleviate the toxicity of APAP, and this appeared clearly by biochemical improvement of kidney function parameters and antioxidant parameters. But, the alleviation is more pronounced with the both antioxidants. Thus, the pronounce effect of silymarin and N. sativa water extract is most effective in reducing the toxicity induced by APAP and improving the kidney function parameters and antioxidant status of kidney of male mice.

  18. Mitochondrial reactive oxygen species perturb AKT/cyclin D1 cell cycle signaling via oxidative inactivation of PP2A in lowdose irradiated human fibroblasts.

    Science.gov (United States)

    Shimura, Tsutomu; Sasatani, Megumi; Kamiya, Kenji; Kawai, Hidehiko; Inaba, Yohei; Kunugita, Naoki

    2016-01-19

    Here we investigated the cellular response of normal human fibroblasts to repeated exposure to low-dose radiation. In contrast to acute single radiation, low-dose fractionated radiation (FR) with 0.01 Gy/fraction or 0.05 Gy/fraction for 31 days increased in mitochondrial mass, decreased cellular levels of the antioxidant glutathione and caused persistent accumulation of mitochondrial reactive oxygen species (ROS). Excess ROS promoted oxidative inactivation of protein phosphatase PP2A which in turn led to disruption of normal negative feed-back control of AKT/cyclin D1 signaling in cells treated with long-term FR. The resulting abnormal nuclear accumulation of cyclin D1 causes growth retardation, cellular senescence and genome instability in low-dose irradiated cells. Thus, loss of redox control and subsequently elevated levels of ROS perturb signal transduction as a result of oxidative stress. Our study highlights a specific role of mitochondrial ROS in perturbation of AKT/cyclin D1 cell cycle signaling after low-dose long-term FR. The antioxidants N-acetyl-L-cysteine, TEMPO and mitochondrial-targeted antioxidant Mito-TEMPO provided protection against the harmful cell cycle perturbations induced by low-dose long-term FR.

  19. Contribution of reactive oxygen species to the anticancer activity of aminoalkanol derivatives of xanthone.

    Science.gov (United States)

    Sypniewski, Daniel; Szkaradek, Natalia; Loch, Tomasz; Waszkielewicz, Anna M; Gunia-Krzyżak, Agnieszka; Matczyńska, Daria; Sołtysik, Dagna; Marona, Henryk; Bednarek, Ilona

    2017-11-08

    Reactive oxygen species (ROS) are critically involved in the action of anticancer agents. In this study, we investigated the role of ROS in the anticancer mechanism of new aminoalkanol derivatives of xanthone. Most xanthones used in the study displayed significant pro-oxidant effects similar to those of gambogic acid, one of the most active anticancer xanthones. The pro-oxidant activity of our xanthones was shown both directly (by determination of ROS induction, effects on the levels of intracellular antioxidants, and expression of antioxidant enzymes) and indirectly by demonstrating that the overexpression of manganese superoxide dismutase decreases ROS-mediated cell senescence. We also observed that mitochondrial dysfunction and cellular apoptosis enhancement correlated with xanthone-induced oxidative stress. Finally, we showed that the use of the antioxidant N-acetyl-L-cysteine partly reversed these effects of aminoalkanol xanthones. Our results demonstrated that novel aminoalkanol xanthones mediated their anticancer activity primarily through ROS elevation and enhanced oxidative stress, which led to mitochondrial cell death stimulation; this mechanism was similar to the activity of gambogic acid.

  20. Divergent effects of resveratrol, a polyphenolic phytostilbene, on free radical levels and type of cell death induced by the histone deacetylase inhibitors butyrate and trichostatin A.

    Science.gov (United States)

    Galfi, Peter; Jakus, Judit; Molnar, Tamas; Neogrady, Susan; Csordas, Adam

    2005-02-01

    We investigated the effects of the polyphenolic phytostilbene resveratrol on the steady-state free radical (FR) concentration and mode of cell death induced by the histone deacetylase inhibitors butyrate and trichostatin A. (i) There was no correlation between cell death induction by butyrate or trichostatin A (TSA) and FR levels. (ii) Treatment with resveratrol or N-acetyl-l-cystein (NAC) of cells, in which the FR concentration was high, resulted in an almost complete reduction of FR levels. (iii) When, however, the cellular FR concentration was marginal, resveratrol caused a minor, and NAC a marked increase of FRs as well as of the extent of cell death. Thus, resveratrol and NAC acted as antioxidants only when the cellular FR levels were high, and acted as pro-oxidants when facing a low FR concentration. (iv) Since resveratrol and the antioxidant NAC exhibited analogous effects, it is concluded that the observed actions of resveratrol are due to polyphenolic redox reactions and not related to the stilbene moiety of the molecule. (v) The results indicate that the redox status of a given cell type plays an important role in determining whether resveratrol and other antioxidants promote cell death or protect cells from it.

  1. Reactive Oxygen Species Are Required for Human Mesenchymal Stem Cells to Initiate Proliferation after the Quiescence Exit

    Directory of Open Access Journals (Sweden)

    O. G. Lyublinskaya

    2015-01-01

    Full Text Available The present study focuses on the involvement of reactive oxygen species (ROS in the process of mesenchymal stem cells “waking up” and entering the cell cycle after the quiescence. Using human endometrial mesenchymal stem cells (eMSCs, we showed that intracellular basal ROS level is positively correlated with the proliferative status of the cell cultures. Our experiments with the eMSCs synchronized in the G0 phase of the cell cycle revealed a transient increase in the ROS level upon the quiescence exit after stimulation of the cell proliferation. This increase was registered before the eMSC entry to the S-phase of the cell cycle, and elimination of this increase by antioxidants (N-acetyl-L-cysteine, Tempol, and Resveratrol blocked G1–S-phase transition. Similarly, a cell cycle arrest which resulted from the antioxidant treatment was observed in the experiments with synchronized human mesenchymal stem cells derived from the adipose tissue. Thus, we showed that physiologically relevant level of ROS is required for the initiation of human mesenchymal stem cell proliferation and that low levels of ROS due to the antioxidant treatment can block the stem cell self-renewal.

  2. Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage.

    Science.gov (United States)

    González-Ponce, Herson Antonio; Martínez-Saldaña, María Consolación; Rincón-Sánchez, Ana Rosa; Sumaya-Martínez, María Teresa; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han; Jaramillo-Juárez, Fernando

    2016-10-04

    Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-L-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800mg/kg/day, orally) were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally). Rat hepatocyte cultures were exposed to 20mmol/LAPAP, and necrosis was assessed by LDH leakage. Opuntia robusta had significantly higher levels of antioxidants than Opuntia streptacantha. Both extracts significantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts significantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF.

  3. Selenium ameliorates carbimazole induced hepatotoxicity and oxidative stress in Albino rats

    Directory of Open Access Journals (Sweden)

    Saber Abdel-Rahman Sakr

    2015-02-01

    Full Text Available Objective: To evaluate the effect of the antithyroid drug, carbimazole on liver of albino rats and the possible ameliorative role of selenium. Methods: Four groups of rats were used (n=10, Group 1 served as normal control, Group 2 was orally given sodium selenite (10 μg/kg body weight daily for 8 weeks, Group 3 was orally given carbimazole at a dose level of 1.35 mg/kg body weight, Group 4 was orally administered carbimazole and sodium selenite daily for 8 weeks. Rats in control and treated groups were sacrificed by cervical decapitation after 8 weeks of treatment, their livers were removed and stained with H&E for histological examinations. Alanine aminotransferase and aspartate aminotransferase were determined in the sera. Malondialdehyde and the antioxidant enzymes, catalase and superoxide dismutase were measured in the liver. Results: Cytoplasmic vacuolation of the hepatocytes, necrosis, leucocytic infiltrations, blood vessels congestion and fatty degeneration were observed in liver of carbimazole-treated animals. Carbimazole caused marked elevation in serum alanine aminotransferase and aspartate aminotransferase. It also caused an increase in malondialdehyde and depletion of the activity of the antioxidant enzymes, catalase and superoxide dismutase in the liver. Treating animals with carbimazole and selenium led to an improvement in both the histological and biochemical alterations induced by carbimazole. Moreover, selenium reduced the level of malondialdehyde and increased the activity of antioxidant enzymes, superoxide dismutase and catalase. Conclusions: It is concluded that the ameliorative effect of selenium against the hepatotoxicity of carbimazole is attributed to its antioxidant properties.

  4. Biologically Synthesized Gold Nanoparticles Ameliorate Cold and Heat Stress-Induced Oxidative Stress in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Xi-Feng Zhang

    2016-06-01

    Full Text Available Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical, and biological methods have been adopted for their synthesis. Synthetic antioxidants are dangerous to human health. Thus, the search for effective, nontoxic natural compounds with effective antioxidative properties is essential. Although AuNPs have been studied for use in various biological applications, exploration of AuNPs as antioxidants capable of inhibiting oxidative stress induced by heat and cold stress is still warranted. Therefore, one goal of our study was to produce biocompatible AuNPs using biological methods that are simple, nontoxic, biocompatible, and environmentally friendly. Next, we aimed to assess the antioxidative effect of AuNPs against oxidative stress induced by cold and heat in Escherichia coli, which is a suitable model for stress responses involving AuNPs. The response of aerobically grown E. coli cells to cold and heat stress was found to be similar to the oxidative stress response. Upon exposure to cold and heat stress, the viability and metabolic activity of E. coli was significantly reduced compared to the control. In addition, levels of reactive oxygen species (ROS and malondialdehyde (MDA and leakage of proteins and sugars were significantly elevated, and the levels of lactate dehydrogenase activity (LDH and adenosine triphosphate (ATP significantly lowered compared to in the control. Concomitantly, AuNPs ameliorated cold and heat-induced oxidative stress responses by increasing the expression of antioxidants, including glutathione (GSH, glutathione S-transferase (GST, super oxide dismutase (SOD, and catalase (CAT. These consistent physiology and biochemical data suggest that AuNPs can ameliorate cold and

  5. Antioxidant-Induced Stress

    Directory of Open Access Journals (Sweden)

    Robert D. Kross

    2012-02-01

    Full Text Available Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these “drugs”. The normal balance between antioxidants and free radicals in the body is offset when either of these forces prevails. The available evidence on the harmful effects of antioxidants is analyzed in this review. In summary, a hypothesis is presented that “antioxidant-induced stress” results when antioxidants overwhelm the body’s free radicals.

  6. 27 CFR 24.178 - Amelioration.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Amelioration. 24.178 Section 24.178 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT..., during and after fermentation. The fixed acid level of the juice is determined prior to fermentation and...

  7. Ameliorative effects of selenium and zinc

    African Journals Online (AJOL)

    Methidathion-induced hematological, biochemical and hepatohistological alterations in rat: Ameliorative effects of selenium and zinc. ... In contrast, reduced glutathione level (GSH), and the activities of catalase (CAT), superoxide dismutase (SOD), and the glutathione peroxidase (GPx) content of hepatic tissue decreased ...

  8. Ameliorative effect of Lentinus squarrosulus mycomeat against ...

    African Journals Online (AJOL)

    Ameliorative effect of Lentinus squarrosulus mycomeat against Pseudomonas aeruginosa infection using albino rat as animal model. ... The increasing awareness of inherent therapeutic and prophylactic benefits of some higher fungi and their products has been the recent trend for improving a healthy vigour. Mycomeat is a ...

  9. Amelioration of radiation nephropathy by acetylsalicylic acid

    NARCIS (Netherlands)

    Verheij, M.; Stewart, F. A.; Oussoren, Y.; Weening, J. J.; Dewit, L.

    1995-01-01

    This investigation was carried out to assess the amelioration by two antithrombotic drugs of radiation nephropathy in mice. Mouse kidneys were given split-dose irradiation to total doses between 17 and 22 Gy. A first group of animals was given acetylsalicylic acid (ASA) in drinking water, a second

  10. Cannabidiol treatment ameliorates ischemia/reperfusion renal injury in rats.

    Science.gov (United States)

    Fouad, Amr A; Al-Mulhim, Abdulruhman S; Jresat, Iyad

    2012-09-17

    To investigate the protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, against renal ischemia/reperfusion injury in rats. Bilateral renal ischemia was induced for 30 min followed by reperfusion for 24h. Cannabidiol (5mg/kg, i.v.) was given 1h before and 12h following the procedure. Ischemia/reperfusion caused significant elevations of serum creatinine and renal malondialdehyde and nitric oxide levels, associated with a significant decrease in renal reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters induced by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced kidney damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in ischemic/reperfused kidney tissue. Cannabidiol, via its antioxidant and anti-inflammatory properties, may represent a potential therapeutic option to protect against ischemia/reperfusion renal injury. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. The Ameliorative Effects of L-2-Oxothiazolidine-4-Carboxylate on Acetaminophen-Induced Hepatotoxicity in Mice

    Directory of Open Access Journals (Sweden)

    Jun Ho Shin

    2013-03-01

    Full Text Available The aim of the study was to investigate the ameliorative effects and the mechanism of action of L-2-oxothiazolidine-4-carboxylate (OTC on acetaminophen (APAP-induced hepatotoxicity in mice. Mice were randomly divided into six groups: normal control group, APAP only treated group, APAP + 25 mg/kg OTC, APAP + 50 mg/kg OTC, APAP + 100 mg/kg OTC, and APAP + 100 mg/kg N-acetylcysteine (NAC as a reference control group. OTC treatment significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels in a dose dependent manner. OTC treatment was markedly increased glutathione (GSH production and glutathione peroxidase (GSH-px activity in a dose dependent manner. The contents of malondialdehyde and 4-hydroxynonenal in liver tissues were significantly decreased by administration of OTC and the inhibitory effect of OTC was similar to that of NAC. Moreover, OTC treatment on APAP-induced hepatotoxicity significantly reduced the formation of nitrotyrosin and terminal deoxynucleotidyl transferase dUTP nick end labeling positive areas of liver tissues in a dose dependent manner. Furthermore, the activity of caspase-3 in liver tissues was reduced by administration of OTC in a dose dependent manner. The ameliorative effects of OTC on APAP-induced liver damage in mice was similar to that of NAC. These results suggest that OTC has ameliorative effects on APAP-induced hepatotoxicity in mice through anti-oxidative stress and anti-apoptotic processes.

  12. Administration of Ketamine Causes Autophagy and Apoptosis in the Rat Fetal Hippocampus and in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Xinran Li

    2018-02-01

    Full Text Available Drug abuse during pregnancy is a serious problem. Like alcohol, anticonvulsants, sedatives, and anesthetics, such as ketamine, can pass through the placental barrier and affect the growing fetus. However, the mechanism by which ketamine causes damage to fetal rats is not well understood. Therefore, in this study, we anesthetized pregnant rats with ketamine and evaluated the Total Antioxidant Capacity (T-AOC, Reactive Oxygen Species (ROS, and Malondialdehyde (MDA. Moreover, we determined changes in the levels of Cleaved-Caspase-3 (C-Caspase-3, Beclin-1, B-cell lymphoma-2 (Bcl-2, Bcl-2 Associated X Protein (Bax, Autophagy-related gene 4 (Atg4, Atg5, p62 (SQSTM1, and marker of autophagy Light Chain 3 (LC3. In addition, we cultured PC12 cells in vitro to determine the relationship between ROS, autophagy, and apoptosis following ketamine treatment. The results showed that ketamine induced changes in autophagy- and apoptosis-related proteins, reduced T-AOC, and generated excessive levels of ROS and MDA. In vitro experiments showed similar results, indicating that apoptosis levels can be inhibited by 3-MA. We also found that autophagy and apoptosis can be inhibited by N-acetyl-L-cysteine (Nac. Thus, anesthesia with ketamine in pregnant rats may increase the rate of autophagy and apoptosis in the fetal hippocampus and the mechanism may be through inhibition of antioxidant activity and ROS accumulation.

  13. Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

    International Nuclear Information System (INIS)

    Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

    2009-01-01

    Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

  14. Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells

    Science.gov (United States)

    Costello, James C.; Liesa, Marc; Morones-Ramirez, J Ruben; Slomovic, Shimyn; Molina, Anthony; Shirihai, Orian S.; Collins, James J.

    2013-01-01

    Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics—quinolones, aminoglycosides, and β-lactams—cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic–induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-L-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people. PMID:23825301

  15. Pro-oxidant effect of melatonin in tumour leucocytes: relation with its cytotoxic and pro-apoptotic effects.

    Science.gov (United States)

    Bejarano, Ignacio; Espino, Javier; Barriga, Carmen; Reiter, Russel J; Pariente, José A; Rodríguez, Ana B

    2011-01-01

    Melatonin has many effects on a wide range of physiological functions and is involved in a number of pathological events including oncostatic and neoplastic processes. The tissue protective actions of melatonin are attributed to its well-known antioxidant activity though melatonin might also exert pro-oxidant effects, particularly in tumour cells. This study evaluated the pro-oxidant effects of melatonin in tumour cell lines of human haematopoietic origin. Melatonin treatment is able to stimulate production of intracellular reactive oxygen species (ROS), as revealed by the increase in rhodamine-123 fluorescence, which was associated with significant cytotoxicity and activation of caspase activities. Furthermore, pre-treatment of cells with well-known antioxidants, such as N-acetyl-L-cysteine (NAC), trolox, PEG-catalase and reduced glutathione (GSH), reversed the effects of melatonin on both intracellular ROS production, as on the cytotoxicity and caspase activation. This pro-oxidant action of melatonin may assist in limiting tumour cell growth. © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.

  16. N-acetyl-l-cystine (NAC) protects against H9N2 swine influenza virus-induced acute lung injury.

    Science.gov (United States)

    Zhang, Rui-Hua; Li, Chun-Hong; Wang, Cun-Lian; Xu, Ming-Ju; Xu, Tong; Wei, Dong; Liu, Bao-Jian; Wang, Guo-Hua; Tian, Shu-Fei

    2014-09-01

    The antioxidant N-acetyl-l-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on H9N2 swine influenza virus-induced acute lung injury (ALI) were investigated in mice. BALB/c mice were inoculated intranasally with 10(7) 50% tissue culture infective doses (TCID(50)) of A/swine/HeBei/012/2008/(H9N2) viruses with or without NAC treatments to induce ALI model. The result showed that pulmonary inflammation, pulmonary edema, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6, IL-1β and CXCL-10 in BALF were attenuated by NAC. Moreover, our data showed that NAC significantly inhibited the levels of TLR4 protein and TLR4 mRNA in the lungs. Pharmacological inhibitors of TLR4 (E5564) exerted similar effects like those determined for NAC in H9N2 swine influenza virus-infected mice. These results suggest that antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. In Vitro and In Vivo Properties of Ellagic Acid in Malaria Treatment▿

    Science.gov (United States)

    Soh, Patrice Njomnang; Witkowski, Benoît; Olagnier, David; Nicolau, Marie-Laure; Garcia-Alvarez, Maria-Concepcion; Berry, Antoine; Benoit-Vical, Françoise

    2009-01-01

    Malaria is one of the most significant causes of infectious disease in the world. The search for new antimalarial chemotherapies has become increasingly urgent due to the parasites’ resistance to current drugs. Ellagic acid is a polyphenol found in various plant products. In this study, antimalarial properties of ellagic acid were explored. The results obtained have shown high activity in vitro against all Plasmodium falciparum strains whatever their levels of chloroquine and mefloquine resistance (50% inhibitory concentrations ranging from 105 to 330 nM). Ellagic acid was also active in vivo against Plamodium vinckei petteri in suppressive, curative, and prophylactic murine tests, without any toxicity (50% effective dose by the intraperitoneal route inferior to 1 mg/kg/day). The study of the point of action of its antimalarial activity in the erythrocytic cycle of Plasmodium falciparum demonstrated that it occurred at the mature trophozoite and young schizont stages. Moreover, ellagic acid has been shown to potentiate the activity of current antimalarial drugs such as chloroquine, mefloquine, artesunate, and atovaquone. This study also proved the antioxidant activity of ellagic acid and, in contrast, the inhibitory effect of the antioxidant compound N-acetyl-l-cysteine on its antimalarial efficacy. The possible mechanisms of action of ellagic acid on P. falciparum are discussed in light of the results. Ellagic acid has in vivo activity against plasmodia, but modification of the compound could lead to improved pharmacological properties, principally for the oral route. PMID:19015354

  18. Ganoderma atrum polysaccharide ameliorates ROS generation and apoptosis in spleen and thymus of immunosuppressed mice.

    Science.gov (United States)

    Li, Wen-Juan; Li, Lu; Zhen, Weng-Ya; Wang, Le-Feng; Pan, Meng; Lv, Jia-Qian; Wang, Fan; Yao, Yu-Fei; Nie, Shao-Ping; Xie, Ming-Yong

    2017-01-01

    Ganoderma atrum polysaccharide (PSG-1) is a bioactive compound with antioxidant and immunomodulatory activities. The aim of this study was to determine the effect of PSG-1 on reactive oxygen species (ROS) generation and apoptosis in spleen and thymus of cyclophosphamide (CTX)-induced immunosuppressed mice. The results showed that PSG-1 protected mice against CTX-mediated immunosuppression, as evidenced by enhancing the ratios of thymus and spleen weights to body weight, promoting T cell and B cell survival, and increasing levels of TNF-α and IL-2. Apoptosis, ROS generation and lipid peroxidation in the immune organs of the immunosuppressed animals were ameliorated by PSG-1. The immune benefits of PSG-1 were associated with the enhancement of the activities of glutathione peroxidase, superoxide dismutase and catalase in the immune organs, implying that antioxidant activities of PSG-1 may play an important role in PSG-1-evoked immune protection. Taken together, these findings have demonstrated that PSG-1 may ameliorate CTX-induced immunosuppression through reducing apoptosis and oxidative damage in immunological system. Copyright © 2016. Published by Elsevier Ltd.

  19. Phytoestrogen -zearalanol ameliorates memory impairment and neuronal DNA oxidation in ovariectomized mice

    Directory of Open Access Journals (Sweden)

    Yilong Dong

    2013-09-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the effect of a novel phytoestrogen, α-Zearalanol, on Alzheimer's disease-related memory impairment and neuronal oxidation in ovariectomized mice. METHODS: Female C57/BL6 mice were ovariectomized or received sham operations and treatment with equivalent doses of 17β-estradiol or α-Zearalanol for 8 weeks. Their spatial learning and memory were analyzed using the Morris water maze test. The antioxidant enzyme activities and reactive oxygen species generation, neuronal DNA oxidation, and MutT homolog 1 expression in the hippocampus were measured. RESULTS: Treatment with 17β-estradiol or α-Zearalanol significantly improved spatial learning and memory performance in ovariectomized mice. In addition, 17β-estradiol and α-Zearalanol attenuated the decrease in antioxidant enzyme activities and increased reactive oxygen species production in ovariectomized mice. The findings indicated a significant elevation in hippocampi neuronal DNA oxidation and reduction in MutT homolog 1 expression in estrogen-deficient mice, but supplementation with 17β-estradiol or α-Zearalanol efficaciously ameliorated this situation. CONCLUSION: These results demonstrate that α-Zearalanol is potentially beneficial for improving memory impairments and neuronal oxidation damage in a manner similar to that of 17β-estradiol. Therefore, the compound may be a potential therapeutic agent that can ameliorate neurodegenerative disorders related to estrogen deficiency.

  20. Treatment with dimethyl fumarate ameliorates liver ischemia/reperfusion injury.

    Science.gov (United States)

    Takasu, Chie; Vaziri, Nosratola D; Li, Shiri; Robles, Lourdes; Vo, Kelly; Takasu, Mizuki; Pham, Christine; Farzaneh, Seyed H; Shimada, Mitsuo; Stamos, Michael J; Ichii, Hirohito

    2017-07-07

    To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). Rats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined. Histological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. DMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.

  1. Antioxidant Strategies in the Management of Diabetic Neuropathy

    Directory of Open Access Journals (Sweden)

    Ayodeji Babatunde Oyenihi

    2015-01-01

    Full Text Available Chronic hyperglycaemia (an abnormally high glucose concentration in the blood resulting from defects in insulin secretion/action, or both, is the major hallmark of diabetes in which it is known to be involved in the progression of the condition to different complications that include diabetic neuropathy. Diabetic neuropathy (diabetes-induced nerve damage is the most common diabetic complication and can be devastating because it can lead to disability. There is an increasing body of evidence associating diabetic neuropathy with oxidative stress. Oxidative stress results from the production of oxygen free radicals in the body in excess of its ability to eliminate them by antioxidant activity. Antioxidants have different mechanisms and sites of actions by which they exert their biochemical effects and ameliorate nerve dysfunction in diabetes by acting directly against oxidative damage. This review will examine different strategies for managing diabetic neuropathy which rely on exogenous antioxidants.

  2. Fine chalk dust induces inflammatory response via p38 and ERK MAPK pathway in rat lung.

    Science.gov (United States)

    Zhang, Yuexia; Yang, Zhenhua; Chen, Yunzhu; Li, Ruijin; Geng, Hong; Dong, Wenjuan; Cai, Zongwei; Dong, Chuan

    2018-01-01

    Chalk teaching is widely used in the world due to low cost, especially in some developing countries. During teaching with chalks, a large amount of fine chalk dust is produced. Although exposure to chalk dust is associated with respiratory diseases, the mechanism underlying the correlation between chalk dust exposure and adverse effects has not fully been elucidated. In this study, inflammation and its signal pathway in rat lungs exposed to fine chalk dust were examined through histopathology analyses; pro-inflammatory gene transcription; and protein levels measured by HE staining, RT-PCR, and western blot analysis. The results demonstrated that fine chalk dust increased neutrophils and up-regulated inflammatory gene mRNA levels (TNF-α, IL-6, TGF-β1, iNOS, and ICAM-1), and oxidative stress marker (HO-1) level, leading to the increase of inflammatory cell infiltration and inflammatory injury on the lungs. These inflammation responses were mediated, at least in part, via p38 and extracellular regulated proteinase (ERK) mitogen-activated protein kinase (MAPK) signaling mechanisms. In contrast, N-acetyl-L-cysteine (NAC) supplement significantly ameliorated these changes in inflammatory responses. Our results support the hypothesis that fine chalk dust can damage rat lungs and the NAC supplement may attenuate fine chalk dust-associated lung inflammation.

  3. Antioxidant cosmeto-textiles: skin assessment.

    Science.gov (United States)

    Alonso, Cristina; Martí, Meritxell; Martínez, Vanessa; Rubio, Laia; Parra, José L; Coderch, Luisa

    2013-05-01

    penetrated through the skin layers when cosmeto-textiles were used compared to direct topical application of the antioxidant solution. The cosmeto-textiles investigated can act as a reservoir system capable of progressively deliver the active substance to the skin layers. From the skin penetration profiles and the antioxidant efficacy assessment of resveratrol, it is possible to ameliorate the inherent antioxidant capacity of skin. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Possible ameliorative effects of kolaviron against reproductive toxicity in sub-lethally whole body gamma-irradiated rats.

    Science.gov (United States)

    Adaramoye, Oluwatosin A; Adedara, Isaac A; Farombi, E Olatunde

    2012-05-01

    Ionizing radiation is one of the environmental factors that may contribute to reproductive dysfunction by a mechanism involving oxidative stress. We investigated the possible ameliorative effects of kolaviron (KV) (a biflavonoid from the seeds of Garcinia kola) on sperm characteristics, testicular lipid peroxidation (LPO) and antioxidant status after a whole body γ-irradiation in Wistar rats. Vitamin C (VC) served as standard antioxidant in this study. The study consists of four groups of 6 rats each. Group I received corn oil, whereas group II received a single dose of γ-radiation (5 Gy). The animals in groups III and IV were pretreated with KV (250 mg/kg) and VC (250 mg/kg) by oral gavage five times in a week, respectively, for 6 weeks prior to and 8 weeks after exposure to γ-radiation. Gamma-irradiation resulted in a significant (pin body weight and relative testes weight. Also, γ-irradiation significantly (pin the serum and testes. Irradiated rats showed testicular degeneration with concomitant decrease in sperm motility and viability. Although sperm abnormalities significantly increased, it has no effect on the epididymal sperm count. KV and VC significantly (prats. Furthermore, supplementation of KV and VC ameliorated radiation-induced toxicity by increasing the activities of antioxidant enzymes, decreased LPO and abrogated testicular degeneration. Taken together, γ-irradiation caused reproductive dysfunction by depleting the antioxidant defence system in the rats, while administration of KV or VC ameliorated the radiation-induced testicular toxicity. Copyright © 2010 Elsevier GmbH. All rights reserved.

  5. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    International Nuclear Information System (INIS)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy; Pillai, Ayyappan Harikrishna; Harikumar, Sankaran Kutty; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-01-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  6. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  7. Antioxidants Protect against Arsenic Induced Mitochondrial Cardio-Toxicity

    Directory of Open Access Journals (Sweden)

    Clare Pace

    2017-12-01

    Full Text Available Arsenic is a potent cardiovascular toxicant associated with numerous biomarkers of cardiovascular diseases in exposed human populations. Arsenic is also a carcinogen, yet arsenic trioxide is used as a therapeutic agent in the treatment of acute promyelotic leukemia (APL. The therapeutic use of arsenic is limited due to its severe cardiovascular side effects. Many of the toxic effects of arsenic are mediated by mitochondrial dysfunction and related to arsenic’s effect on oxidative stress. Therefore, we investigated the effectiveness of antioxidants against arsenic induced cardiovascular dysfunction. A growing body of evidence suggests that antioxidant phytonutrients may ameliorate the toxic effects of arsenic on mitochondria by scavenging free radicals. This review identifies 21 antioxidants that can effectively reverse mitochondrial dysfunction and oxidative stress in cardiovascular cells and tissues. In addition, we propose that antioxidants have the potential to improve the cardiovascular health of millions of people chronically exposed to elevated arsenic concentrations through contaminated water supplies or used to treat certain types of leukemias. Importantly, we identify conceptual gaps in research and development of new mito-protective antioxidants and suggest avenues for future research to improve bioavailability of antioxidants and distribution to target tissues in order reduce arsenic-induced cardiovascular toxicity in a real-world context.

  8. Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Hajime Otani

    2013-01-01

    Full Text Available Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span.

  9. Antioxidants in liver health

    Science.gov (United States)

    Casas-Grajales, Sael; Muriel, Pablo

    2015-01-01

    Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. PMID:26261734

  10. Inhibition of invasion and induction of apoptosis by curcumin in H-ras-transformed MCF10A human breast epithelial cells.

    Science.gov (United States)

    Kim, M S; Kang, H J; Moon, A

    2001-08-01

    Curcumin, a dietary pigment in turmeric, posseses anti-carcinogenic and anti-metastatic properties. The present study was conducted to study in vitro chemopreventive effects of curcumin in transformed breast cells. Here, we show that curcumin inhibits H-ras-induced invasive phenotype in MCF10A human breast epithelial cells (H-ras MCF10A) and downregulates matrix metalloproteinase (MMP)-2 dose-dependently. Curcumin exerted cytotoxic effect on H-ras MCF10A cells in a concentration-dependent manner. Curcumin-induced cell death was mainly due to apoptosis in which a prominent downregulation of Bcl-2 and upregulation of Bax were involved. We also suggest a possible involvement of caspase-3 in curcumin-induced apoptosis. Curcumin treatment resulted in the production of reactive oxygen species (ROS) in H-ras MCF10A cells. Apoptotic event by curcumin was significantly inhibited by pretreatment of an antioxidant N-acetyl-L-cysteine (NAC), suggesting redox signaling as a mechanism responsible for curcumin-induced apoptosis in H-ras MCF10A cells. Taken together, our results demonstrate that curcumin inhibits invasion and induces apoptosis, proving the chemopreventive potential of curcumin.

  11. Corosolic Acid Induces Non-Apoptotic Cell Death through Generation of Lipid Reactive Oxygen Species Production in Human Renal Carcinoma Caki Cells

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    Seon Min Woo

    2018-04-01

    Full Text Available Corosolic acid is one of the pentacyclic triterpenoids isolated from Lagerstroemia speciose and has been reported to exhibit anti-cancer and anti-proliferative activities in various cancer cells. In the present study, we investigated the molecular mechanisms of corosolic acid in cancer cell death. Corosolic acid induces a decrease of cell viability and an increase of cell cytotoxicity in human renal carcinoma Caki cells. Corosolic acid-induced cell death is not inhibited by apoptosis inhibitor (z-VAD-fmk, a pan-caspase inhibitor, necroptosis inhibitor (necrostatin-1, or ferroptosis inhibitors (ferrostatin-1 and deferoxamine (DFO. Furthermore, corosolic acid significantly induces reactive oxygen species (ROS levels, but antioxidants (N-acetyl-l-cysteine (NAC and trolox do not inhibit corosolic acid-induced cell death. Interestingly, corosolic acid induces lipid oxidation, and α-tocopherol markedly prevents corosolic acid-induced lipid peroxidation and cell death. Anti-chemotherapeutic effects of α-tocopherol are dependent on inhibition of lipid oxidation rather than inhibition of ROS production. In addition, corosolic acid induces non-apoptotic cell death in other renal cancer (ACHN and A498, breast cancer (MDA-MB231, and hepatocellular carcinoma (SK-Hep1 and Huh7 cells, and α-tocopherol markedly inhibits corosolic acid-induced cell death. Therefore, our results suggest that corosolic acid induces non-apoptotic cell death in cancer cells through the increase of lipid peroxidation.

  12. OGG1 Involvement in High Glucose-Mediated Enhancement of Bupivacaine-Induced Oxidative DNA Damage in SH-SY5Y Cells

    Science.gov (United States)

    Liu, Zhong-Jie; Zhao, Wei; Zhang, Qing-Guo; Li, Le; Lai, Lu-Ying; Jiang, Shan; Xu, Shi-Yuan

    2015-01-01

    Hyperglycemia can inhibit expression of the 8-oxoG-DNA glycosylase (OGG1) which is one of the key repair enzymes for DNA oxidative damage. The effect of hyperglycemia on OGG1 expression in response to local anesthetics-induced DNA damage is unknown. This study was designed to determine whether high glucose inhibits OGG1 expression and aggravates bupivacaine-induced DNA damage via reactive oxygen species (ROS). SH-SY5Y cells were cultured with or without 50 mM glucose for 8 days before they were treated with 1.5 mM bupivacaine for 24 h. OGG1 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. ROS was estimated using the redox-sensitive fluorescent dye DCFH-DA. DNA damage was investigated with immunostaining for 8-oxodG and comet assays. OGG1 expression was inhibited in cells exposed to high glucose with concomitant increase in ROS production and more severe DNA damage as compared to control culture conditions, and these changes were further exacerbated by bupivacaine. Treatment with the antioxidant N-acetyl-L-cysteine (NAC) prevented high glucose and bupivacaine mediated increase in ROS production and restored functional expression of OGG1, which lead to attenuated high glucose-mediated exacerbation of bupivacaine neurotoxicity. Our findings indicate that subjects with diabetes may experience more detrimental effects following bupivacaine use. PMID:26161242

  13. Phloretin induces cell cycle arrest and apoptosis of human glioblastoma cells through the generation of reactive oxygen species.

    Science.gov (United States)

    Liu, Yuanyuan; Fan, Chenghe; Pu, Lv; Wei, Cui; Jin, Haiqiang; Teng, Yuming; Zhao, Mingming; Yu, Albert Cheung Hoi; Jiang, Feng; Shu, Junlong; Li, Fan; Peng, Qing; Kong, Jian; Pan, Bing; Zheng, Lemin; Huang, Yining

    2016-06-01

    Phloretin, a flavonoid present in various plants, has been reported to exert anticarcinogenic effects. However, the mechanism of its chemo-preventive effect on human glioblastoma cells is not fully understood. This study aimed to investigate the molecular mechanism of phloretin and its associated chemo-preventive effect in human glioblastoma cells. The results indicate that phloretin inhibited cell proliferation by inducing cell cycle arrest at the G0-G1 phase and induced apoptosis of human glioblastoma cells. Phloretin-induced cell cycle arrest was associated with increased expression of p27 and decreased expression of cdk2, cdk4, cdk6, cyclinD and cyclinE. Moreover, the PI3K/AKT/mTOR signaling cascades were suppressed by phloretin in a dose-dependent manner. In addition, phloretin triggered the mitochondrial apoptosis pathway and generated reactive oxygen species (ROS). This was accompanied by the up-regulation of Bax, Bak and c-PARP and the down-regulation of Bcl-2. The antioxidant agents N-acetyl-L-cysteine and glutathione weakened the effect of phloretin on glioblastoma cells. In conclusion, these results demonstrate that phloretin exerts potent chemo-preventive activity in human glioblastoma cells through the generation of ROS.

  14. Calf Spleen Extractive Injection (CSEI, a small peptides enriched extraction, induces human hepatocellular carcinoma cell apoptosis via ROS/MAPKs dependent mitochondrial pathway

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    Dongxu Jia

    2016-10-01

    Full Text Available Calf Spleen Extractive Injection (CSEI, a small peptides enriched extraction, performs immunomodulatory activity on cancer patients suffering from radiotherapy or chemotherapy. The present study aims to investigate the anti-hepatocellular carcinoma effects of CSEI in cells and tumor-xenografted mouse models. In HepG2 and SMMC-7721 cells, CSEI reduced cell viability, enhanced apoptosis rate, caused reactive oxygen species (ROS accumulation, inhibited migration ability, and induced caspases cascade and mitochondrial membrane potential dissipation. CSEI significantly inhibited HepG2-xenografted tumor growth in nude mice. In cell and animal experiments, CSEI increased the activations of pro-apoptotic proteins including caspase 8, caspase 9 and caspase 3; meanwhile, it suppressed the expressions of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2 and anti-oxidation proteins, such as nuclear factor-erythroid 2 related factor 2 (Nrf2 and catalase (CAT. The enhanced phosphorylation of P38 and c-JunN-terminalkinase (JNK, and decreased phosphorylation of extra cellular signal-regulated protein kinase (ERKs were observed in CSEI-treated cells and tumor tissues. CSEI-induced cell viability reduction was significantly attenuated by N-Acetyl-l-cysteine (a ROS inhibitor pretreatment. All data demonstrated that the upregulated oxidative stress status and the altered mitogen-activated protein kinases (MAPKs phosphorylation contributed to CSEI-driven mitochondrial dysfunction. Taken together, CSEI exactly induced apoptosis in human hepatocellular carcinoma cells via ROS/MAPKs dependent mitochondrial pathway.

  15. Asperlin induces G2/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells

    International Nuclear Information System (INIS)

    He, Long; Nan, Mei-Hua; Oh, Hyun Cheol; Kim, Young Ho; Jang, Jae Hyuk; Erikson, Raymond Leo; Ahn, Jong Seog; Kim, Bo Yeon

    2011-01-01

    Highlights: → A new anti-cancer effect of an antibiotics, asperlin, is exploited. → Asperlin induced human cervical cancer cell apoptosis through ROS generation. → Asperlin activated DNA-damage related ATM protein and cell cycle associated proteins. → Asperlin could be developed as a new anti-cancer therapeutics. -- Abstract: We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.

  16. Asperlin induces G₂/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells.

    Science.gov (United States)

    He, Long; Nan, Mei-Hua; Oh, Hyun Cheol; Kim, Young Ho; Jang, Jae Hyuk; Erikson, Raymond Leo; Ahn, Jong Seog; Kim, Bo Yeon

    2011-06-10

    We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions

    Science.gov (United States)

    Pidoux, Guillaume; Gerbaud, Pascale; Guibourdenche, Jean; Thérond, Patrice; Ferreira, Fatima; Simasotchi, Christelle; Evain-Brion, Danièle; Gil, Sophie

    2015-01-01

    The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST), which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT). Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2). Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac), an antioxidant. PMID:26186596

  18. Role of Oxidative Stress in the Induction of Metallothionein-2A and Heme Oxygenase-1 Gene Expression by the Antineoplastic Agent Gallium Nitrate in Human Lymphoma Cells

    Science.gov (United States)

    Yang, Meiying; Chitambar, Christopher R.

    2008-01-01

    The mechanisms of action of gallium nitrate, an antineoplastic drug, are only partly understood. Using a DNA microarray to examine genes induced by gallium nitrate in CCRF-CEM cells, we found that gallium increased metallothionein-2A (MT2A) and heme oxygenase-1 (HO-1) gene expression and altered the levels of other stress-related genes. MT2A and HO-1 were increased after 6 and 16 h of incubation with gallium nitrate. An increase in oxidative stress, evidenced by a decrease in cellular GSH and GSH/GSSG ratio, and an increase in dichlorodihydrofluoroscein (DCF) fluorescence, was seen after 1 – 4 h incubation of cells with gallium nitrate. DCF fluorescence was blocked by the mitochondria-targeted antioxidant mitoquinone. N-acetyl-L-cysteine blocked gallium-induced MT2A and HO-1 expression and increased gallium’s cytotoxicity. Studies with a zinc-specific fluoroprobe suggested that gallium produced an expansion of an intracellular labile zinc pool, suggesting an action of gallium on zinc homeostasis. Gallium nitrate increased the phosphorylation of p38 mitogen-activated protein kinase and activated Nrf-2, a regulator of HO-1 gene transcription. Gallium-induced Nrf-2 activation and HO-1 expression were diminished by a p38 MAP kinase inhibitor. We conclude that gallium nitrate induces cellular oxidative stress as an early event which then triggers the expression of HO-1 and MT2A through different pathways. PMID:18586083

  19. A novel andrographolide derivative AL-1 exerts its cytotoxicity on K562 cells through a ROS-dependent mechanism.

    Science.gov (United States)

    Zhu, Yong-Yang; Yu, Guangchuang; Zhang, Ye; Xu, Zheng; Wang, Yu-Qiang; Yan, Guang-Rong; He, Qing-Yu

    2013-01-01

    Andrographolide-lipoic acid conjugate (AL-1) is a new in-house synthesized chemical entity, which was derived by covalently linking andrographolide with lipoic acid. However, its anti-cancer effect and cytotoxic mechanism remains unknown. In this study, we found that AL-1 could significantly inhibit cell viability of human leukemia K562 cells by inducing G2/M arrest and apoptosis in a dose-dependent manner. Thirty-one AL-1-regulated protein alterations were identified by proteomics analysis. Gene ontology and ingenuity pathway analysis revealed that a cluster of proteins of oxidative redox state and apoptotic cell death-related proteins, such as PRDX2, PRDX3, PRDX6, TXNRD1, and GLRX3, were regulated by AL-1. Functional studies confirmed that AL-1 induced apoptosis of K562 cells through a ROS-dependent mechanism, and anti-oxidant, N-acetyl-L-cysteine, could completely block AL-1-induced cytotoxicity, implicating that ROS generation played a vital role in AL-1 cytotoxicity. Accumulated ROS resulted in oxidative DNA damage and subsequent G2/M arrest and mitochondrial-mediated apoptosis. The current work reveals that a novel andrographolide derivative AL-1 exerts its anticancer cytotoxicity through a ROS-dependent DNA damage and mitochondrial-mediated apoptosis mechanism. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. N-3 Polyunsaturated Fatty Acids Decrease the Protein Expression of Soluble Epoxide Hydrolase via Oxidative Stress-Induced P38 Kinase in Rat Endothelial Cells.

    Science.gov (United States)

    Okada, Takashi; Morino, Katsutaro; Nakagawa, Fumiyuki; Tawa, Masashi; Kondo, Keiko; Sekine, Osamu; Imamura, Takeshi; Okamura, Tomio; Ugi, Satoshi; Maegawa, Hiroshi

    2017-06-24

    N -3 polyunsaturated fatty acids (PUFAs) improve endothelial function. The arachidonic acid-derived metabolites (epoxyeicosatrienoic acids (EETs)) are part of the endothelial hyperpolarization factor and are vasodilators independent of nitric oxide. However, little is known regarding the regulation of EET concentration by docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in blood vessels. Sprague-Dawley rats were fed either a control or fish oil diet for 3 weeks. Compared with the control, the fish oil diet improved acetylcholine-induced vasodilation and reduced the protein expression of soluble epoxide hydrolase (sEH), a key EET metabolic enzyme, in aortic strips. Both DHA and EPA suppressed sEH protein expression in rat aorta endothelial cells (RAECs). Furthermore, the concentration of 4-hydroxy hexenal (4-HHE), a lipid peroxidation product of n -3 PUFAs, increased in n -3 PUFA-treated RAECs. In addition, 4-HHE treatment suppressed sEH expression in RAECs, suggesting that 4-HHE (derived from n -3 PUFAs) is involved in this phenomenon. The suppression of sEH was attenuated by the p38 kinase inhibitor (SB203580) and by treatment with the antioxidant N-acetyl-L-cysteine. In conclusion, sEH expression decreased after n -3 PUFAs treatment, potentially through oxidative stress and p38 kinase. Mild oxidative stress induced by n -3 PUFAs may contribute to their cardio-protective effect.

  1. 2-Deoxy-D-glucose treatment of endothelial cells induces autophagy by reactive oxygen species-mediated activation of the AMP-activated protein kinase.

    Directory of Open Access Journals (Sweden)

    Qilong Wang

    2011-02-01

    Full Text Available Autophagy is a cellular self-digestion process activated in response to stresses such as energy deprivation and oxidative stress. However, the mechanisms by which energy deprivation and oxidative stress trigger autophagy remain undefined. Here, we report that activation of AMP-activated protein kinase (AMPK by mitochondria-derived reactive oxygen species (ROS is required for autophagy in cultured endothelial cells. AMPK activity, ROS levels, and the markers of autophagy were monitored in confluent bovine aortic endothelial cells (BAEC treated with the glycolysis blocker 2-deoxy-D-glucose (2-DG. Treatment of BAEC with 2-DG (5 mM for 24 hours or with low concentrations of H(2O(2 (100 µM induced autophagy, including increased conversion of microtubule-associated protein light chain 3 (LC3-I to LC3-II, accumulation of GFP-tagged LC3 positive intracellular vacuoles, and increased fusion of autophagosomes with lysosomes. 2-DG-treatment also induced AMPK phosphorylation, which was blocked by either co-administration of two potent anti-oxidants (Tempol and N-Acetyl-L-cysteine or overexpression of superoxide dismutase 1 or catalase in BAEC. Further, 2-DG-induced autophagy in BAEC was blocked by overexpressing catalase or siRNA-mediated knockdown of AMPK. Finally, pretreatment of BAEC with 2-DG increased endothelial cell viability after exposure to hypoxic stress. Thus, AMPK is required for ROS-triggered autophagy in endothelial cells, which increases endothelial cell survival in response to cell stress.

  2. Cas Ilgly Induces Apoptosis in Glioma C6 Cells In Vitro and In Vivo through Caspase-Dependent and Caspase-Independent Mechanisms

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    Cristina Trejo-Solís

    2005-06-01

    Full Text Available In this work, we investigated the effects of Casiopeina Il-gly (Cas ILgly—a new copper compound exhibiting antineoplastic activity—on glioma C6 cells under both in vitro and in vivo conditions, as an approach to identify potential therapeutic agents against malignant glioma. The exposure of C6 cells to Cas Ilgly significantly inhibited cell proliferation, increased reactive oxygen species (ROS formation, and induced apoptosis in a dose-dependent manner. In cultured C6 cells, Cas Ilgly caused mitochondrio-nuclear translocation of apoptosis induction factor (AIF and endonuclease G at all concentrations tested; in contrast, fragmentation of nucleosomal DNA, cytochrome c release, and caspase-3 activation were observed at high concentrations. Administration of N-acetyl-l-cystein, an antioxidant, resulted in significant inhibition of AIF translocation, nucleosomal DNA fragmentation, and caspase-3 activation induced by Cas Ilgly. These results suggest that caspase-dependent and caspase-independent pathways both participate in apoptotic events elicited by Cas Ilgly. ROS formation induced by Cas Ilgly might also be involved in the mitochondrio-nuclear translocation of AIF and apoptosis. In addition, treatment of glioma C6-positive rats with Cas Ilgly reduced tumor volume and mitotic and cell proliferation indexes, and increased apoptotic index. Our findings support the use of Cas Ilgly for the treatment of malignant gliomas.

  3. Cannabidiol-induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase-8

    International Nuclear Information System (INIS)

    Wu, H.-Y.; Chu, R.-M.; Wang, C.-C.; Lee, C.-Y.; Lin, S.-H.; Jan, T.-R.

    2008-01-01

    We recently reported that cannabidiol (CBD) exhibited a generalized suppressive effect on T-cell functional activities in splenocytes directly exposed to CBD in vitro or isolated from CBD-administered mice. To investigate the potential mechanisms of CBD effects on T cells, we characterized the pro-apoptotic effect of CBD on primary lymphocytes. The apoptosis of splenocytes was markedly enhanced following CBD exposure in a time- and concentration-dependent manner, as evidenced by nuclear hypodiploidity and DNA strand breaks. Exposure of splenocytes to CBD elicited an early production of reactive oxygen species (ROS) with the peak response at 1 h post CBD treatment. In parallel with the ROS production, a gradual diminishment in the cellular glutathione (GSH) content was detected in CBD-treated splenocytes. Both CBD-mediated ROS production and GSH diminishment were remarkably attenuated by the presence of N-acetyl-L-cysteine (NAC), a thiol antioxidant. In addition, CBD treatment significantly stimulated the activation of caspase-8, which was abrogated in the presence of NAC or GSH. Pretreatment of splenocytes with a cell-permeable inhibitor for caspase-8 significantly attenuated, in a concentration-dependent manner, CBD-mediated apoptosis, but not ROS production. Collectively, the present study demonstrated that the apoptotic effect of CBD in primary lymphocytes is closely associated with oxidative stress-dependent activation of caspase-8

  4. Cannabidiol induced a contrasting pro-apoptotic effect between freshly isolated and precultured human monocytes

    International Nuclear Information System (INIS)

    Wu, Hsin-Ying; Chang, An-Chi; Wang, Chia-Chi; Kuo, Fu-Hua; Lee, Chi-Ya; Liu, Der-Zen; Jan, Tong-Rong

    2010-01-01

    It has been documented that cannabidiol (CBD) induced apoptosis in a variety of transformed cells, including lymphocytic and monocytic leukemias. In contrast, a differential sensitivity between normal lymphocytes and monocytes to CBD-mediated apoptosis has been reported. The present study investigated the pro-apoptotic effect of CBD on human peripheral monocytes that were either freshly isolated or precultured for 72 h. CBD markedly enhanced apoptosis of freshly isolated monocytes in a time- and concentration-dependent manner, whereas precultured monocytes were insensitive. By comparison, both cells were sensitive to doxorubicin-induced apoptosis. CBD significantly diminished the cellular thiols and glutathione in freshly isolated monocytes. The apoptosis induced by CBD was abrogated in the presence of N-acetyl- L -cysteine, a precursor of glutathione. In addition, precultured monocytes contained a significantly greater level of glutathione and heme oxygenase-1 (HO-1) compared to the freshly isolated cells. The HO-1 competitive inhibitor zinc protoporphyrin partially but significantly restored the sensitivity of precultured monocytes to CBD-mediated apoptosis. Collectively, our results demonstrated a contrasting pro-apoptotic effect of CBD between precultured and freshly isolated monocytes, which was closely associated with the cellular level of glutathione and the antioxidative capability of the cells.

  5. TNF-α promotes extracellular vesicle release in mouse astrocytes through glutaminase.

    Science.gov (United States)

    Wang, Kaizhe; Ye, Ling; Lu, Hongfang; Chen, Huili; Zhang, Yanyan; Huang, Yunlong; Zheng, Jialin C

    2017-04-20

    Extracellular vesicles (EVs) are membrane-contained vesicles shed from cells. EVs contain proteins, lipids, and nucleotides, all of which play important roles in intercellular communication. The release of EVs is known to increase during neuroinflammation. Glutaminase, a mitochondrial enzyme that converts glutamine to glutamate, has been implicated in the biogenesis of EVs. We have previously demonstrated that TNF-α promotes glutaminase expression in neurons. However, the expression and the functionality of glutaminase in astrocytes during neuroinflammation remain unknown. We posit that TNF-α can promote the release of EVs in astrocytes through upregulation of glutaminase expression. Release of EVs, which was demonstrated by electron microscopy, nanoparticle tracking analysis (NTA), and Western Blot, increased in mouse astrocytes when treated with TNF-α. Furthermore, TNF-α treatment significantly upregulated protein levels of glutaminase and increased the production of glutamate, suggesting that glutaminase activity is increased after TNF-α treatment. Interestingly, pretreatment with a glutaminase inhibitor blocked TNF-α-mediated generation of reactive oxygen species in astrocytes, which indicates that glutaminase activity contributes to stress in astrocytes during neuroinflammation. TNF-α-mediated increased release of EVs can be blocked by either the glutaminase inhibitor, antioxidant N-acetyl-L-cysteine, or genetic knockout of glutaminase, suggesting that glutaminase plays an important role in astrocyte EV release during neuroinflammation. These findings suggest that glutaminase is an important metabolic factor controlling EV release from astrocytes during neuroinflammation.

  6. Pre-Transplantation Blockade of TNF-α-Mediated Oxygen Species Accumulation Protects Hematopoietic Stem Cells.

    Science.gov (United States)

    Ishida, Takashi; Suzuki, Sachie; Lai, Chen-Yi; Yamazaki, Satoshi; Kakuta, Shigeru; Iwakura, Yoichiro; Nojima, Masanori; Takeuchi, Yasuo; Higashihara, Masaaki; Nakauchi, Hiromitsu; Otsu, Makoto

    2017-04-01

    Hematopoietic stem cell (HSC) transplantation (HSCT) for malignancy requires toxic pre-conditioning to maximize anti-tumor effects and donor-HSC engraftment. While this induces bone marrow (BM)-localized inflammation, how this BM environmental change affects transplanted HSCs in vivo remains largely unknown. We here report that, depending on interval between irradiation and HSCT, residence within lethally irradiated recipient BM compromises donor-HSC reconstitution ability. Both in vivo and in vitro we demonstrate that, among inflammatory cytokines, TNF-α plays a role in HSC damage: TNF-α stimulation leads to accumulation of reactive oxygen species (ROS) in highly purified hematopoietic stem/progenitor cells (HSCs/HSPCs). Transplantation of flow-cytometry-sorted murine HSCs reveals damaging effects of accumulated ROS on HSCs. Short-term incubation either with an specific inhibitor of tumor necrosis factor receptor 1 signaling or an antioxidant N-acetyl-L-cysteine (NAC) prevents TNF-α-mediated ROS accumulation in HSCs. Importantly, pre-transplantation exposure to NAC successfully demonstrats protective effects in inflammatory BM on graft-HSCs, exhibiting better reconstitution capability than that of nonprotected control grafts. We thus suggest that in vivo protection of graft-HSCs from BM inflammation is a feasible and attractive approach, which may lead to improved hematopoietic reconstitution kinetics in transplantation with myeloablative conditioning that inevitably causes inflammation in recipient BM. Stem Cells 2017;35:989-1002. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  7. Apoptosis signal-regulating kinase 1 mediates denbinobin-induced apoptosis in human lung adenocarcinoma cells

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    Pan Shiow-Lin

    2009-05-01

    Full Text Available Abstract In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1 in denbinobin-induced apoptosis in human lung adenocarcinoma (A549 cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN, two antioxidants (N-acetyl-L-cysteine (NAC and glutathione (GSH, a c-Jun N-terminal kinase (JNK inhibitor (SP600125, and an activator protein-1 (AP-1 inhibitor (curcumin. Treatment of A549 cells with denbinobin caused increases in ASK1 activity and reactive oxygen species (ROS production, and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH, and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS production to cause JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results in A549 cell apoptosis.

  8. Ameliorative Effects of Herbal Combinations in Hyperlipidemia

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    Nishant P. Visavadiya

    2011-01-01

    Full Text Available The roots of Glycyrrhiza glabra, Withania somnifera, Asparagus racemosus, and Chlorophytum borivilianum and seeds of Sesamum indicum are ayurvedic medicinal plants used in India to treat several ailments. Our previous studies indicated that these plants possess hypolipidemic and antioxidant potential. The present study was aimed at investigating the composite effects of these plants on hypercholesterolemic rats. Three different combinations (5 gm%, given for four weeks used in this study effectively reduced plasma and hepatic lipid profiles and increased fecal excretion of cholesterol, neutral sterol, and bile acid along with increasing the hepatic HMG-CoA reductase activity and bile acid content in hypercholesterolemic rats. Further, all three combinations also improved the hepatic antioxidant status (catalase, SOD, and ascorbic acid levels and plasma total antioxidant capacity with reduced hepatic lipid peroxidation. Overall, combination I had the maximum effect on hypercholesterolemic rats followed by combinations II and III due to varying concentrations of the different classes of phytocomponents.

  9. Ameliorative effects of herbal combinations in hyperlipidemia.

    Science.gov (United States)

    Visavadiya, Nishant P; Narasimhacharya, A V R L

    2011-01-01

    The roots of Glycyrrhiza glabra, Withania somnifera, Asparagus racemosus, and Chlorophytum borivilianum and seeds of Sesamum indicum are ayurvedic medicinal plants used in India to treat several ailments. Our previous studies indicated that these plants possess hypolipidemic and antioxidant potential. The present study was aimed at investigating the composite effects of these plants on hypercholesterolemic rats. Three different combinations (5 gm%, given for four weeks) used in this study effectively reduced plasma and hepatic lipid profiles and increased fecal excretion of cholesterol, neutral sterol, and bile acid along with increasing the hepatic HMG-CoA reductase activity and bile acid content in hypercholesterolemic rats. Further, all three combinations also improved the hepatic antioxidant status (catalase, SOD, and ascorbic acid levels) and plasma total antioxidant capacity with reduced hepatic lipid peroxidation. Overall, combination I had the maximum effect on hypercholesterolemic rats followed by combinations II and III due to varying concentrations of the different classes of phytocomponents.

  10. Amelioration of testosterone induced benign prostatic hyperplasia by Prunus species.

    Science.gov (United States)

    Jena, Ashish Kumar; Vasisht, Karan; Sharma, Neetika; Kaur, Ramdeep; Dhingra, Mamta Sachdeva; Karan, Maninder

    2016-08-22

    Benign prostatic hyperplasia (BPH) is a common urological disorder of men. The ethnomedicinal use of an African plant Prunus africana (Hook.f.) Kalkman (Pygeum) in treating men's problems made it a popular remedy all over the globe for the treatment of BPH and related disorders. However, rampant collections made from the wild in Africa have pushed the plant to Appendix II of CITES demanding conservation of the species. In the present study, the aim was to unearth the protective effect of bark of different species of Prunus against BPH. The five selected Indian plants of family Rosaceae viz. Prunus amygdalus Stokes, Prunus armeniaca L., Prunus cerasoides Buch.-Ham. ex D. Don, Prunus domestica L. and Prunus persica (L.) Batsch were evaluated against P. africana (Hook.f.) Kalkman for a suitable comparison of efficacy as antiBPH agents. The antiBPH activity was evaluated in testosterone (2mg/kg/day, s.c, 21 days) induced BPH in Wistar rats. The parameters studied were body weights; histopathological examination, immunohistochemistry (PCNA) and biochemical estimations of the prostate; supported by prostatic index, testicular index, creatinine, testosterone levels; antioxidant and anti-inflammatory evaluation. The study also included chemical profiling using three markers (β-sitosterol, docosyl ferulate and ursolic acid) and estimation of β-sitosterol content through GC. The Prunus species showed the presence of all the three markers in their TLC fingerprint profile and maximum amount of β-sitosterol by GC was observed in P. domestica. Interestingly, all the species exhibited significant amelioration in testosterone induced parameters with P. domestica showing the most encouraging effect as indicated from histopathological examination, immunohistochemistry and biochemical studies. The Prunus species further showed remarkable anti-inflammatory and antioxidant activity signifying their role in interfering with various possible factors involved in BPH. These findings are

  11. Extract of Moringa oleifera leaves ameliorates streptozotocin-induced Diabetes mellitus in adult rats.

    Science.gov (United States)

    Yassa, Hanan Dawood; Tohamy, Adel Fathy

    2014-06-01

    Medicinal plants attract growing interest in the therapeutic management of Diabetes mellitus. Moringa oleifera is a remarkably nutritious vegetable with several antioxidant properties. The present study assessed the possible antioxidant and antidiabetic effects of an aqueous extract of M. oleifera leaves in treating streptozotocin-induced diabetic albino rats. The antidiabetic effects of aqueous extract of M. oleifera leaves were assessed histomorphometrically, ultrastructurally and biochemically. Fasting plasma glucose (FPG) was monitored and morphometric measurements of β-cells of islets of Langerhans (modified Gomori's stain) and collagen fibers (Mallory's trichrome stain) were performed. The antioxidant effects of M. oleifera leaves were determined by measuring the reduced glutathione and lipid peroxidation product, malondialdehyde, in pancreatic tissue. M. oleifera treatment significantly ameliorated the altered FPG (from 380% to 145%), reduced glutathione (from 22% to 73%) and malondialdehyde (from 385% to 186%) compared to control levels. The histopathological damage of islet cells was also markedly reversed. Morphometrically, M. oleifera significantly increased the areas of positive purple modified Gomori stained β-cells (from 60% to 91%) and decreased the area percentage of collagen fibers (from 199% to 120%) compared to control values. Experimental findings clearly indicate the potential benefits of using the aqueous extract of M. oleifera leaves as a potent antidiabetic treatment. Copyright © 2014 Elsevier GmbH. All rights reserved.

  12. Ameliorative Influence of Green Tea Extract on Copper Nanoparticle-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Ibrahim, Marwa A; Khalaf, A A; Galal, Mona K; Ogaly, Hanan A; H M Hassan, Azza

    2015-12-01

    The potential toxicity of copper nanoparticles (CNPs) to the human health and environment remains a critical issue. In the present study, we investigated the protective influence of an aqueous extract of green tea leaves (GTE) against CNPs-induced (20-30 nm) hepatotoxicity. Four different groups of rats were used: group I was the control, group II received CNPs (40 mg/kg BW), group III received CNPs plus GTE, and group IV received GTE alone. We highlighted the hepatoprotective effect of GTE against CNPs toxicity through monitoring the alteration of liver enzyme activity, antioxidant defense mechanism, histopathological alterations, and DNA damage evaluation. The rats that were given CNPs only had a highly significant elevation in liver enzymes, alteration in oxidant-antioxidant balance, and severe pathological changes. In addition, we detected a significant elevation of DNA fragmentation percentage, marked DNA laddering, and significance over expression of both caspase-3 and Bax proteins. The findings for group III clarify the efficacy of GTE as a hepatoprotectant on CNPs through improving the liver enzyme activity, antioxidant status, as well as suppressing DNA fragmentation and the expression of the caspase-3 and Bax proteins. In conclusion, GTE was proved to be a potential hepatoprotective additive as it significantly ameliorates the hepatotoxicity and apoptosis induced by CNPs.

  13. Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

    Directory of Open Access Journals (Sweden)

    Joo Wan Kim

    2015-01-01

    Full Text Available The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF on sciatic neurectomy- (NTX- induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation.

  14. Ameliorative Influence of Green Tea Extract on Copper Nanoparticle-Induced Hepatotoxicity in Rats

    Science.gov (United States)

    Ibrahim, Marwa A.; Khalaf, A. A.; Galal, Mona K.; Ogaly, Hanan A.; H. M. Hassan, Azza

    2015-09-01

    The potential toxicity of copper nanoparticles (CNPs) to the human health and environment remains a critical issue. In the present study, we investigated the protective influence of an aqueous extract of green tea leaves (GTE) against CNPs-induced (20-30 nm) hepatotoxicity. Four different groups of rats were used: group I was the control, group II received CNPs (40 mg/kg BW), group III received CNPs plus GTE, and group IV received GTE alone. We highlighted the hepatoprotective effect of GTE against CNPs toxicity through monitoring the alteration of liver enzyme activity, antioxidant defense mechanism, histopathological alterations, and DNA damage evaluation. The rats that were given CNPs only had a highly significant elevation in liver enzymes, alteration in oxidant-antioxidant balance, and severe pathological changes. In addition, we detected a significant elevation of DNA fragmentation percentage, marked DNA laddering, and significance over expression of both caspase-3 and Bax proteins. The findings for group III clarify the efficacy of GTE as a hepatoprotectant on CNPs through improving the liver enzyme activity, antioxidant status, as well as suppressing DNA fragmentation and the expression of the caspase-3 and Bax proteins. In conclusion, GTE was proved to be a potential hepatoprotective additive as it significantly ameliorates the hepatotoxicity and apoptosis induced by CNPs.

  15. Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

    Science.gov (United States)

    Kim, Joo Wan; Ku, Sae-Kwang; Kim, Ki Young; Kim, Sung Goo; Han, Min Ho; Kim, Gi-Young; Hwang, Hye Jin; Kim, Byung Woo; Kim, Cheol Min

    2015-01-01

    The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation. PMID:26064425

  16. Amelioration of nitrobenzene-induced nephrotoxicity by the ethanol extract of the herb Euphorbia hirta.

    Science.gov (United States)

    Suganya, Subramanian; Sophia, Dominic; Raj, Chinthamony Arul; Rathi, Muthaiyan Ahalliya; Thirumoorthi, Lakshmanan; Meenakshi, Periyasamy; Kumar, Dugganaboyana Guru; Gopalakrishnan, Velliyur Kanniyapan

    2011-07-01

    Euphorbia hirta (L.) (Euphorbiaceae) is a very popular herb amongst practitioners of traditional medicine and used in the treatment of female disorders, respiratory ailments, tumors, jaundice, digestive problems, wounds, etc. We aimed to evaluate the protective effect of E. hirta against nitrobenzene-induced nephrotoxicity in albino rats. The nephroprotective activity of the ethanol extract of E. hirta (400 mg/kg body weight) was studied in nitrobenzene-induced albino rats (1000 mg/kg body weight). The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and the levels of reduced glutathione (GSH), total thiols and vitamin C in the kidney tissues were determined. Histopathologic investigation was performed in the kidney tissue samples. Nitrobenzene administration significantly (P hirta significantly normalized the antioxidant levels. The nephroprotective activity was also supported by histopathologic studies of kidney tissue. The results indicate that the ethanol extract of E. hirta ameliorates renal dysfunction and could be used as an effective protector against nitrobenzene-induced nephrotoxicity, primarily through its antioxidant capacity.

  17. Activity-dependent neuroprotective protein (ADNP)-derived peptide (NAP) ameliorates hypobaric hypoxia induced oxidative stress in rat brain.

    Science.gov (United States)

    Sharma, Narendra K; Sethy, Niroj K; Meena, Ram Niwas; Ilavazhagan, Govindsamy; Das, Mainak; Bhargava, Kalpana

    2011-06-01

    Hypobaric hypoxia is a socio-economic problem affecting cognitive, memory and behavior functions. Severe oxidative stress caused by hypobaric hypoxia adversely affects brain areas like cortex, hippocampus, basal ganglia, and cerebellum. In the present study, we have investigated the antioxidant and memory protection efficacy of the synthetic NAP peptide (NAPVSIPQ) during long-term chronic hypobaric hypoxia (7, 14, 21 and 28 days, 25,000ft) in rats. Intranasal supplementation of NAP peptide (2μg/Kg body weight) improved antioxidant status of brain evaluated by biochemical assays for free radical estimation, lipid peroxidation, GSH and GSSG level. Analysis of expression levels of SOD revealed that NAP significantly activated antioxidant genes as compared to hypoxia exposed rats. We have also observed a significant increased expression of Nrf2, the master regulator of antioxidant defense system and its downstream targets such as HO-1, GST and SOD1 by NAP supplementation, suggesting activation of Nrf2-mediated antioxidant defense response. In corroboration, our results also demonstrate that NAP supplementation improved the memory function assessed with radial arm maze. These cumulative results suggest the therapeutic potential of NAP peptide for ameliorating hypobaric hypoxia-induced oxidative stress. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Antioxidants of Edible Mushrooms.

    Science.gov (United States)

    Kozarski, Maja; Klaus, Anita; Jakovljevic, Dragica; Todorovic, Nina; Vunduk, Jovana; Petrović, Predrag; Niksic, Miomir; Vrvic, Miroslav M; van Griensven, Leo

    2015-10-27

    Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants can effectively improve defense mechanisms, but because of their adverse toxic effects under certain conditions, preference is given to natural compounds. Consequently, the requirements for natural, alternative sources of antioxidant foods identified in edible mushrooms, as well as the mechanistic action involved in their antioxidant properties, have increased rapidly. Chemical composition and antioxidant potential of mushrooms have been intensively studied. Edible mushrooms might be used directly in enhancement of antioxidant defenses through dietary supplementation to reduce the level of oxidative stress. Wild or cultivated, they have been related to significant antioxidant properties due to their bioactive compounds, such as polyphenols, polysaccharides, vitamins, carotenoids and minerals. Antioxidant and health benefits, observed in edible mushrooms, seem an additional reason for their traditional use as a popular delicacy food. This review discusses the consumption of edible mushrooms as a powerful instrument in maintaining health, longevity and life quality.

  19. Antioxidants of Edible Mushrooms

    Directory of Open Access Journals (Sweden)

    Maja Kozarski

    2015-10-01

    Full Text Available Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants can effectively improve defense mechanisms, but because of their adverse toxic effects under certain conditions, preference is given to natural compounds. Consequently, the requirements for natural, alternative sources of antioxidant foods identified in edible mushrooms, as well as the mechanistic action involved in their antioxidant properties, have increased rapidly. Chemical composition and antioxidant potential of mushrooms have been intensively studied. Edible mushrooms might be used directly in enhancement of antioxidant defenses through dietary supplementation to reduce the level of oxidative stress. Wild or cultivated, they have been related to significant antioxidant properties due to their bioactive compounds, such as polyphenols, polysaccharides, vitamins, carotenoids and minerals. Antioxidant and health benefits, observed in edible mushrooms, seem an additional reason for their traditional use as a popular delicacy food. This review discusses the consumption of edible mushrooms as a powerful instrument in maintaining health, longevity and life quality.

  20. Tomato pomace powder ameliorated cisplatin-induced ...

    African Journals Online (AJOL)

    Tomato (Lycopersicon esculentum) pomace powder (TPP) may be a preventive agent by virtue of its known antioxidant property. The possible protective role of TPP against cisplatin-induced alteration of the microanatomy of rat brain was investigated. Thirty rats were divided equally into five groups: control, propylene glycol ...

  1. Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity – Exploring the armoury of obscurity

    Directory of Open Access Journals (Sweden)

    Kanchanlata Singh

    2018-02-01

    The effect of supplementation of thirteen different antioxidants and their analogues as a single agent or in combination with chemotherapy has been compiled in this article. The present review encompasses a total of 174 peer-reviewed original articles from 1967 till date comprising 93 clinical trials with a cumulative number of 18,208 patients, 56 animal studies and 35 in vitro studies. Our comprehensive data suggests that antioxidant has superior potential of ameliorating chemotherapeutic induced toxicity. Antioxidant supplementation during chemotherapy also promises higher therapeutic efficiency and increased survival times in patients.

  2. Acetylcholinesterase inhibition ameliorates deficits in motivational drive

    Directory of Open Access Journals (Sweden)

    Martinowich Keri

    2012-03-01

    Full Text Available Abstract Background Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes. Methods We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes. Results CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens. Conclusions Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.

  3. Cacao polyphenols ameliorate autoimmune myocarditis in mice.

    Science.gov (United States)

    Zempo, Hirofumi; Suzuki, Jun-ichi; Watanabe, Ryo; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2016-04-01

    Myocarditis is a clinically severe disease; however, no effective treatment has been established. The aim of this study was to determine whether cacao bean (Theobroma cacao) polyphenols ameliorate autoimmune myocarditis. We used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. Mice with induced EAM were treated with a cacao polyphenol extract (CPE, n=12) or vehicle (n=12). On day 21, hearts were harvested and analyzed. Elevated heart weight to body weight and fibrotic area ratios as well as high cardiac cell infiltration were observed in the vehicle-treated EAM mice. However, these increases were significantly suppressed in the CPE-treated mice. Reverse transcriptase-PCR revealed that mRNA expressions of interleukin (Il)-1β, Il-6, E-selectin, vascular cell adhesion molecule-1 and collagen type 1 were lower in the CPE group compared with the vehicle group. The mRNA expressions of nicotinamide adenine dinucleotide phosphate-oxidase (Nox)2 and Nox4 were increased in the vehicle-treated EAM hearts, although CPE treatment did not significantly suppress the transcription levels. However, compared with vehicle treatment of EAM hearts, CPE treatment significantly suppressed hydrogen peroxide concentrations. Cardiac myeloperoxidase activity, the intensity of dihydroethidium staining and the phosphorylation of nuclear factor-κB p65 were also lower in the CPE group compared with the vehicle group. Our data suggest that CPE ameliorates EAM in mice. CPE is a promising dietary supplement to suppress cardiovascular inflammation and oxidative stress.

  4. Antioxidants of edible mushrooms

    NARCIS (Netherlands)

    Kozarski, Maja; Klaus, Anita; Jakovljevic, Dragica; Todorovic, Nina; Vunduk, Jovana; Petrović, Predrag; Niksic, Miomir; Vrvic, Miroslav M.; Griensven, Van Leo

    2015-01-01

    Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic

  5. Seabuckthorn (Hippophae rhamnoides L.) leaf extract ameliorates the gamma radiation mediated DNA damage and hepatic alterations

    International Nuclear Information System (INIS)

    Khan, Amitava; Manna, Krishnendu; Das, Dipesh Kr; Sinha, Mahuya; Kesh, Swaraj Bandhu; Das, Ujjal; Dey, Sanjit; Chinchubose; Banerji, Asoke; Dey, Rakhi Sharma

    2014-01-01

    In vitro assessment showed that H. rhumnoides (HrLE) extract possessed free radical scavenging activities and can protect gamma (γ) radiation induced supercoiled DNA damage. For in vivo study, Swiss albino mice were administered with HrLE (30 mg/kg body weight) for 15 consecutive days before exposing them to a single dose of 5 Gy of γ radiation. HrLE significantly prevented the radiation induced genomic DNA damage indicated as a significant reduction in the comet parameters. The lipid peroxidation, liver function enzymes, expression of phosphorylated NFkB (p65) and IkBα: Ba increased whereas the endogenous antioxidants diminished upon radiation exposure compared to control. Pretreatment of HrLE extract ameliorated these changes. Based on the present results it can be concluded that H. rhamnoides possess a potential preventive element in planned and accidental nuclear exposures. (author)

  6. Amelioration of bromobenzene hepatotoxicity by Withania somnifera pretreatment: Role of mitochondrial oxidative stress

    Directory of Open Access Journals (Sweden)

    Mahima Vedi

    2014-01-01

    Full Text Available The present study investigated the possible protective role of Withania somnifera (Linn. Dunal (Solanaceae root powder against bromobenzene-induced oxidative damage in rat liver mitochondria. Administration of bromobenzene (10 mmol/kg body weight to rats resulted in increased levels of liver marker enzymes, lipid peroxidation, TNF-α, IL-1β and VEGF. There was also marked depletion in the levels of mitochondrial enzymes and antioxidant activity. Pre-treatment with W. somnifera significantly decreased the levels of liver marker enzymes, TNF-α, IL-1β, VEGF and ameliorated histopathological manifestations in bromobenzene-treated rats. The molecular docking analysis predicted that the pro-inflammatory mediator NF-κB showed significant interaction with selected various active components of W. somnifera (withaferin A, withanolide D and withanolide E. This study demonstrates a good protective effect of W. somnifera against bromobenzene-induced oxidative stress.

  7. Amelioration of bromobenzene hepatotoxicity byWithania somniferapretreatment: Role of mitochondrial oxidative stress.

    Science.gov (United States)

    Vedi, Mahima; Rasool, Mahaboobkhan; Sabina, Evan Prince

    2014-01-01

    The present study investigated the possible protective role of Withania somnifera (Linn.) Dunal (Solanaceae) root powder against bromobenzene-induced oxidative damage in rat liver mitochondria. Administration of bromobenzene (10 mmol/kg body weight) to rats resulted in increased levels of liver marker enzymes, lipid peroxidation, TNF-α, IL-1β and VEGF. There was also marked depletion in the levels of mitochondrial enzymes and antioxidant activity. Pre-treatment with W. somnifera significantly decreased the levels of liver marker enzymes, TNF-α, IL-1β, VEGF and ameliorated histopathological manifestations in bromobenzene-treated rats. The molecular docking analysis predicted that the pro-inflammatory mediator NF-κB showed significant interaction with selected various active components of W. somnifera (withaferin A, withanolide D and withanolide E). This study demonstrates a good protective effect of W. somnifera against bromobenzene-induced oxidative stress.

  8. Food-Derived Antioxidant Polysaccharides and Their Pharmacological Potential in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Haifeng Li

    2017-07-01

    Full Text Available Oxidative stress is known to impair architecture and function of cells, which may lead to various chronic diseases, and therefore therapeutic and nutritional interventions to reduce oxidative damages represent a viable strategy in the amelioration of oxidative stress-related disorders, including neurodegenerative diseases. Over the past decade, a variety of natural polysaccharides from functional and medicinal foods have attracted great interest due to their antioxidant functions such as scavenging free radicals and reducing oxidative damages. Interestingly, these antioxidant polysaccharides are also found to attenuate neuronal damages and alleviate cognitive and motor decline in a range of neurodegenerative models. It has recently been established that the neuroprotective mechanisms of polysaccharides are related to oxidative stress-related pathways, including mitochondrial function, antioxidant defense system and pathogenic protein aggregation. Here, we first summarize the current status of antioxidant function of food-derived polysaccharides and then attempt to appraise their anti-neurodegeneration activities.

  9. The performance of maize crop during acid amelioration with ...

    African Journals Online (AJOL)

    Tanzania Journal of Science ... This study evaluated acid ameliorative potential and their effects on maize growth of four organic residues namely wild spikenard, cordia, cowpea and pigeon peas ... The finding suggests different acid ameliorating potential of residues, pigeon peas and cordia being the most effective.

  10. Mitochondrial dysfunction in H9c2 cells during ischemia and amelioration with Tribulus terrestris L.

    Science.gov (United States)

    Reshma, P L; Sainu, Neethu S; Mathew, Anil K; Raghu, K G

    2016-05-01

    The present study investigates the protective effect of partially characterized Tribulus terrestris L. fruit methanol extract against mitochondrial dysfunction in cell based (H9c2) myocardial ischemia model. To induce ischemia, the cells were maintained in an ischemic buffer (composition in mM -137 NaCl, 12 KCl, 0.5 MgCl2, 0.9 CaCl2, 20 HEPES, 20 2-deoxy-d-glucose, pH-6.2) at 37°C with 0.1% O2, 5% CO2, and 95% N2 in a hypoxia incubator for 1h. Cells were pretreated with various concentrations of T. terrestris L. fruit methanol extract (10 and 25μg/ml) and Cyclosporin A (1μM) for 24h prior to the induction of ischemia. Different parameters like lactate dehydrogenase release, total antioxidant capacity, glutathione content and antioxidant enzymes were investigated. Studies were conducted on mitochondria by analyzing alterations in mitochondrial membrane potential, integrity, and dynamics (fission and fusion proteins - Mfn1, Mfn2, OPA1, Drp1 and Fis1). Various biochemical processes in mitochondria like activity of electron transport chain (ETC) complexes, oxygen consumption and ATP production was measured. Ischemia for 1h caused a significant (p≤0.05) increase in LDH leakage, decrease in antioxidant activity and caused mitochondrial dysfunction. T. terrestris L. fruit methanol extract pretreatment was found effective in safeguarding mitochondria via its antioxidant potential, mediated through various bioactives. HPLC of T. terrestris L. fruit methanol extract revealed the presence of ferulic acid, phloridzin and diosgenin. T. terrestris L. fruit ameliorate ischemic insult in H9c2 cells by safeguarding mitochondrial function. This validates the use of T. terrestris L. against heart disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Use of Coffee Pulp and Minerals for Natural Soil Ameliorant

    Directory of Open Access Journals (Sweden)

    Pujiyanto Pujiyanto

    2007-05-01

    Full Text Available In coffee plantation, solid waste of coffee pulp is usually collected as heap nearby processing facilities for several months prior being used as compost. The practice is leading to the formation of odor and liquid which contaminate the environment. Experiments to evaluate the effect of natural soil ameliorant derived from coffee pulp and minerals were conducted at The Indonesian Coffee and Cocoa Research Institute in Jember, East Java. The experiments were intended to optimize the use of coffee pulp to support farming sustainability and minimize negative impacts of solid waste disposal originated from coffee cherry processing. Prior to applications, coffee pulp was hulled to organic paste. The paste was then mixed with 10% minerals (b/b. Composition of the minerals was 50% zeolite and 50% rock phosphate powder. The ameliorant was characterized for their physical and chemical properties. Agronomic tests were conducted on coffee and cocoa seedling. The experiments were arranged according to Randomized Completely Design with 2 factors, consisted of natural ameliorant and inorganic fertilizer respectively. Natural ameliorant derived from coffee pulp was applied at 6 levels: 0, 30, 60, 90, 120 and 150 g dry ameliorant/seedling of 3 kg soil, equivalent to 0, 1, 2, 3, 4 and 5% (b/b of ameliorant respectively. Inorganic fertilizer was applied at 2 levels: 0 and 2 g fertilizer/application of N-P-K compound fertilizer of 15-15-15 respectively. The inorganic fertilizer was applied 4 times during nursery of coffee and cocoa. The result of the experiment indicated that coffee pulp may be used as natural soil ameliorant. Composition of ameliorant of 90% coffee pulp and 10% of minerals has good physical and chemical characteristics for soil amelioration. The composition has high water holding capacity; cations exchange capacity, organic carbon and phosphorus contents which are favorable to increase soil capacity to support plant growth. Application of

  12. Rutin-Enriched Extract from Coriandrum sativum L. Ameliorates Ionizing Radiation-Induced Hematopoietic Injury.

    Science.gov (United States)

    Han, Xiaodan; Xue, Xiaolei; Zhao, Yu; Li, Yuan; Liu, Weili; Zhang, Junling; Fan, Saijun

    2017-04-29

    Hematopoietic injury is a major cause of mortality in radiation accidents and a primary side effect in patients undergoing radiotherapy. Ionizing radiation (IR)-induced myelosuppression is largely attributed to the injury of hematopoietic stem and progenitor cells (HSPCs). Coriander is a culinary herb with multiple pharmacological effects and has been widely used in traditional medicine. In this study, flavonoids were identified as the main component of coriander extract with rutin being the leading compound (rutin-enriched coriander extract; RE-CE). We evaluated the radioprotective effect of RE-CE against IR-induced HSPCs injury. Results showed that RE-CE treatment markedly improved survival, ameliorated organ injuries and myelosuppression, elevated HSPCs frequency, and promoted differentiation and proliferation of HSPCs in irradiated mice. The protective role of RE-CE in hematopoietic injury is probably attributed to its anti-apoptotic and anti-DNA damage effect in irradiated HSPCs. Moreover, these changes were associated with reduced reactive oxygen species (ROS) and enhanced antioxidant enzymatic activities in irradiated HSPCs. Collectively, these findings demonstrate that RE-CE is able to ameliorate IR-induced hematopoietic injury partly by reducing IR-induced oxidative stress.

  13. Plumbagin, a vitamin K3 analogue ameliorate malaria pathogenesis by inhibiting oxidative stress and inflammation.

    Science.gov (United States)

    Gupta, Amit Chand; Mohanty, Shilpa; Saxena, Archana; Maurya, Anil Kumar; Bawankule, Dnyaneshwar U

    2018-03-22

    Plumbagin, a vitamin K3 analogue is the major active constituent in several plants including root of Plumbago indica Linn. This compound has been shown to exhibit a wide spectrum of pharmacological activities. The present investigation was to evaluate the ameliorative effects of plumbagin (PL) against severe malaria pathogenesis due to involvement of oxidative stress and inflammatory response in Plasmodium berghei infected malaria in mice. Malaria pathogenesis was induced by intra-peritoneal injection of P. berghei infected red blood cells into the Swiss albino mice. PL was administered orally at doses of 3, 10 and 30 mg/kg/day following Peter's 4 day suppression test. Oral administration of PL showed significant reduction of parasitaemia and increase in mean survival time. PL treatment is also attributed to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. Significant inhibition in level of oxidative stress and pro-inflammation related markers were observed in PL treated group. The trend of inhibition in oxidative stress markers level after oral treatment of PL was MPO > LPO > ROS in organ injury in P. berghei infected mice. This study showed that plumbagin is able to ameliorate malaria pathogenesis by augmenting anti-oxidative and anti-inflammatory mechanism apart from its effect on reducing parasitaemia and increasing mean survival time of malaria-induced mice.

  14. Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury.

    Science.gov (United States)

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Ban, Tae Hyun; Jang, In-Ae; Yoon, Hye Eun; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2018-01-11

    Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered to aged mice for 6 months. We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont). We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group. Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H 2 O 2 . Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney.

  15. Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Omotayo O. Erejuwa

    2012-01-01

    Full Text Available Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP in spontaneously hypertensive rats (SHR. It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2 and glutathione S-transferase (GST were significantly downregulated while total antioxidant status (TAS and activities of GST and catalase (CAT were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR.

  16. Phytochemical allylguaiacol exerts a neuroprotective effect on hippocampal cells and ameliorates scopolamine-induced memory impairment in mice.

    Science.gov (United States)

    Lim, Hye-Sun; Kim, Bu-Yeo; Kim, Yu Jin; Jeong, Soo-Jin

    2018-02-26

    Allylguaiacol is a phytochemical occurring in various plants such as cloves, cinnamon, basil, and nutmeg. Pharmacological effects of allylguaiacol include antimicrobial, anti-inflammatory, anticancer, antioxidant, and neuroprotective activity. Although allylguaiacol is considered to have neuroprotective effects, there is no report on its regulatory mechanisms at the molecular level. In the present study, we investigated the mechanisms of allylguaiacol as an antioxidant and neuroprotective agent using hydrogen peroxide (H 2 O 2 )-treated HT22 hippocampal cells. Allylguaiacol increased the scavenging activities of free radicals 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH), and enhanced the expression of antioxidant enzymes manganese superoxide dismutase (MnSOD) and catalase. In addition, allylguaiacol inhibited H 2 O 2 -induced damage of HT22 with increasing production of brain-derived neurotrophic factor (BDNF), phosphorylation of phosphoinositide 3-kinase (PI3K), and cyclic AMP response element-binding protein (CREB). Furthermore, antibody microarray data revealed that phospho-regulation of nuclear factor kappa B (NF-κB) p65 and death domain-associated protein (DAXX) is involved in protection against neuronal cell damage. In a mouse model of short-term memory impairment, allylguaiacol (2.5 or 5mg/kg) significantly ameliorated scopolamine-mediated cognitive impairment in a passive avoidance task. In addition, allylguaiacol significantly increased the expression of TrkA and B in the hippocampus from scopolamine-treated mice. Taken together, our findings suggest that allylguaiacol exerts a neuroprotective effect through the antioxidant activation and protein regulation of NF-κB p65 and DAXX-related signaling. The ameliorating effect of allylguaiacol may be useful for treatment of memory impairment in Alzheimer's and its related diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats.

    Science.gov (United States)

    Meena, Sunita; Rajput, Yudhishthir S; Pandey, Amit K; Sharma, Rajan; Singh, Raghvendar

    2016-08-01

    This study was designed to assess anti-diabetic potential of goat, camel, cow and buffalo milk in streptozotocin (STZ) induced type 1 diabetic albino wistar rats. A total of 48 rats were taken for the study where one group was kept as non-diabetic control group (8 rats) while others (40 rats) were made diabetic by STZ (50 mg/kg of body weight) injection. Among diabetic rats, a control group (8 rats) was kept and referred as diabetic control whereas other four groups (8 rats each) of diabetic rats were fed on 50 ml of goat or camel or cow or buffalo milk for 4 weeks. All the rats (non-diabetic and diabetic) were maintained on standard diet for four weeks. STZ administration resulted in enhancement of glucose, total cholesterol, triglyceride, low density lipoprotein, HbA1c and reduction in high density lipoprotein in plasma and lowering of antioxidative enzymes (catalase, glutathione peroxidase and superoxide dismutase) activities in pancreas, kidney, liver and RBCs, coupled with enhanced levels of TBARS and protein carbonyls in pancreas, kidney, liver and plasma. OGTT carried out at the end of 4 week milk feeding indicated that all milks helped in early maintenance of glucose level. All milks reduced atherogenic index. In camel milk fed diabetic group, insulin concentration enhanced to level noted for non-diabetic control while goat, cow and buffalo milk failed to restore insulin level. HbA1c level was also restored only in camel milk fed diabetic group. The level of antioxidative enzymes (catalase, GPx and SOD) in pancreas enhanced in all milk fed groups. Camel milk and to a reasonable extent goat milk reduced formation of TBARS and PCs in tissues and blood. It can be concluded that camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats. Further, only camel milk completely ameliorated oxidative damage in pancreas and normalised insulin level.

  18. Ameliorative Effect of Honey and Propolis Mixture on Rats Exposed to Gamma Irradiation

    International Nuclear Information System (INIS)

    Hemieda, S.F.; Abd-El Nour, K.N.; Hassan, A.I.; Abdou, M.I.; Khalil, W.A.

    2016-01-01

    This study aims to evaluate the ameliorative effect of honey and propolis mixture treatment on some biochemical and biophysical parameters in rats exposed to oxidative stress of gamma irradiation. Male rats were exposed to a fractionated dose gamma irradiation of total 5 Gy in five successive days. A mixture of dose 250 mg/kg/day honey and 90 mg/kg/day propolis was administrated to rats, ten days before irradiation, five days during irradiation and 14 days post irradiation. Blood samples were collected at 1 st , 7 th and 14 th day post the 5 th day of irradiation. Biochemical parameters such as serum liver enzymes (ALT and AST), serum renal function as (BUN and Creatinine) and serum total antioxidants were estimated. Also biophysical studies including hemoglobin investigations (Hb absorption spectra and dielectric measurements) were investigated.The results demonstrated that the levels of AST, ALT, BUN and creatinine were significantly elevated, while levels of total antioxidants were significantly reduced post irradiation. Moreover the absolute values of permittivity ε', dielectric loss ε'' and ac - conductivity σ ac increased in addition to a pronounced decrease in the absorbance at Sort band after irradiation compared to control group.Treatment of the irradiated group with honey and propolis mixture showed significant amelioration in the levels of the biochemical parameters. Also, the values of ε', ε'' and σ ac were nearly close to those of control group. Finally, the average value of peak height of Sort band was significantly increased compared to irradiated rat.

  19. Antioxidants in Translational Medicine

    Science.gov (United States)

    Schmidt, Harald H.H.W.; Stocker, Roland; Vollbracht, Claudia; Paulsen, Gøran; Riley, Dennis

    2015-01-01

    Abstract Significance: It is generally accepted that reactive oxygen species (ROS) scavenging molecules or antioxidants exert health-promoting effects and thus their consumption as food additives and nutraceuticals has been greatly encouraged. Antioxidants may be beneficial in situations of subclinical deficiency and increased demand or acutely upon high-dose infusion. However, to date, there is little clinical evidence for the long-term benefit of most antioxidants. Alarmingly, recent evidence points even to health risks, in particular for supplements of lipophilic antioxidants. Recent Advances: The biological impact of ROS depends not only on their quantities but also on their chemical nature, (sub)cellular and tissue location, and the rates of their formation and degradation. Moreover, ROS serve important physiological functions; thus, inappropriate removal of ROS may cause paradoxical reductive stress and thereby induce or promote disease. Critical Issues: Any recommendation on antioxidants must be based on solid clinical evidence and patient-relevant outcomes rather than surrogate parameters. Future Directions: Such evidence-based use may include site-directed application, time-limited high dosing, (functional) pharmacological repair of oxidized biomolecules, and triggers of endogenous antioxidant response systems. Ideally, these approaches need guidance by patient stratification through predictive biomarkers and possibly imaging modalities. Antioxid. Redox Signal. 23, 1130–1143. PMID:26154592

  20. Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature

    Directory of Open Access Journals (Sweden)

    Abbaszadeh A.

    2017-06-01

    Full Text Available Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/ biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses

  1. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei, E-mail: xmma@bjut.edu.cn; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

    2014-10-01

    Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD{sub 50}) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo

  2. Amelioration of Diabetes and Painful Diabetic Neuropathy by Punica granatum L. Extract and Its Spray Dried Biopolymeric Dispersions.

    Science.gov (United States)

    Raafat, K; Samy, W

    2014-01-01

    Aims. To evaluate the effect of Punica granatum (Pg) rind extract and its spray dried biopolymeric dispersions with casein (F1) or chitosan (F2) against Diabetes mellitus (DM) and diabetic neuropathy (DN). Methods. We measured the acute (6 h) and subacute (8 days) effect of various doses of Pg, F1, and F2 and the active compounds on alloxan-induced DM mouse model. We evaluated DN utilizing latency tests for longer period of time (8 weeks). In addition, the in vivo antioxidant activity was assessed utilizing serum catalase level. Results. The results proved that the highest dose levels of Pg extract, F1, F2 exerted remarkable hypoglycemic activity with 48, 52, and 40% drop in the mice glucose levels after 6 hours, respectively. The tested compounds also improved peripheral nerve function as observed from the latency tests. Bioguided fractionation suggested that gallic acid (GA) was Pg main active ingredient responsible for its actions. Conclusion. Pg extract, F1, F2, and GA could be considered as a new therapeutic potential for the amelioration of diabetic neuropathic pain and the observed in vivo antioxidant potential may be involved in its antinociceptive effect. It is highly significant to pay attention to Pg and GA for amelioration and control of DM and its complications.

  3. Amelioration of Diabetes and Painful Diabetic Neuropathy by Punica granatum L. Extract and Its Spray Dried Biopolymeric Dispersions

    Directory of Open Access Journals (Sweden)

    K. Raafat

    2014-01-01

    Full Text Available Aims. To evaluate the effect of Punica granatum (Pg rind extract and its spray dried biopolymeric dispersions with casein (F1 or chitosan (F2 against Diabetes mellitus (DM and diabetic neuropathy (DN. Methods. We measured the acute (6 h and subacute (8 days effect of various doses of Pg, F1, and F2 and the active compounds on alloxan-induced DM mouse model. We evaluated DN utilizing latency tests for longer period of time (8 weeks. In addition, the in vivo antioxidant activity was assessed utilizing serum catalase level. Results. The results proved that the highest dose levels of Pg extract, F1, F2 exerted remarkable hypoglycemic activity with 48, 52, and 40% drop in the mice glucose levels after 6 hours, respectively. The tested compounds also improved peripheral nerve function as observed from the latency tests. Bioguided fractionation suggested that gallic acid (GA was Pg main active ingredient responsible for its actions. Conclusion. Pg extract, F1, F2, and GA could be considered as a new therapeutic potential for the amelioration of diabetic neuropathic pain and the observed in vivo antioxidant potential may be involved in its antinociceptive effect. It is highly significant to pay attention to Pg and GA for amelioration and control of DM and its complications.

  4. Amelioration of Diabetes and Painful Diabetic Neuropathy by Punica granatum L. Extract and Its Spray Dried Biopolymeric Dispersions

    Science.gov (United States)

    Raafat, K.; Samy, W.

    2014-01-01

    Aims. To evaluate the effect of Punica granatum (Pg) rind extract and its spray dried biopolymeric dispersions with casein (F1) or chitosan (F2) against Diabetes mellitus (DM) and diabetic neuropathy (DN). Methods. We measured the acute (6 h) and subacute (8 days) effect of various doses of Pg, F1, and F2 and the active compounds on alloxan-induced DM mouse model. We evaluated DN utilizing latency tests for longer period of time (8 weeks). In addition, the in vivo antioxidant activity was assessed utilizing serum catalase level. Results. The results proved that the highest dose levels of Pg extract, F1, F2 exerted remarkable hypoglycemic activity with 48, 52, and 40% drop in the mice glucose levels after 6 hours, respectively. The tested compounds also improved peripheral nerve function as observed from the latency tests. Bioguided fractionation suggested that gallic acid (GA) was Pg main active ingredient responsible for its actions. Conclusion. Pg extract, F1, F2, and GA could be considered as a new therapeutic potential for the amelioration of diabetic neuropathic pain and the observed in vivo antioxidant potential may be involved in its antinociceptive effect. It is highly significant to pay attention to Pg and GA for amelioration and control of DM and its complications. PMID:24982685

  5. Antioxidative properties of flavonoids

    NARCIS (Netherlands)

    Bowedes, T.C.F.; Luttikhold, J.; Stijn, van M.F.M.; Visser, M.; Norren, van K.; Vermeulen, M.A.R.; Leeuwen, P.A.M.

    2011-01-01

    Evidence accumulates that a family of plant compounds, known as flavonoids, can prevent or slow down the progression of cardiovascular diseases, cancer, inflammatory and neurodegenerative diseases. Flavonoids are considered beneficial, this is often attributed to their powerful antioxidant

  6. Atmospheric oxidation and antioxidants

    CERN Document Server

    Meurant, Gerard

    1993-01-01

    Volume I reviews current understanding of autoxidation, largely on the basis of the reactions of oxygen with characterised chemicals. From this flows the modern mechanism of antioxidant actions and their application in stabilisation technology.

  7. Plasma antioxidants from chocolate

    OpenAIRE

    Serafini, M.; Bugianesi, R.; Maiani, G.; Valtuena, S.; De Santis, S.; Crozier, A.

    2003-01-01

    There is some speculation that dietary flavonoids from chocolate, in particular (-)epicatechin, may promote cardiovascular health as a result of direct antioxidant effects or through antithrombotic mechanisms. Here we show that consumption of plain, dark chocolate results in an increase in both the total antioxidant capacity and the (-)epicatechin content of blood plasma, but that these effects are markedly reduced when the chocolate is consumed with milk or if milk is incorporated as milk ch...

  8. Antioxidant supplements and mortality

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Nikolova, Dimitrinka; Gluud, Christian

    2014-01-01

    Oxidative damage to cells and tissues is considered involved in the aging process and in the development of chronic diseases in humans, including cancer and cardiovascular diseases, the leading causes of death in high-income countries. This has stimulated interest in the preventive potential of a...... of antioxidant supplements. Today, more than one half of adults in high-income countries ingest antioxidant supplements hoping to improve their health, oppose unhealthy behaviors, and counteract the ravages of aging....

  9. Antioxidant properties of flavonoids

    Directory of Open Access Journals (Sweden)

    Sofna D.S. Banjarnahor

    2015-01-01

    Full Text Available Flavonoids represent a remarkable group of plant secondary metabolites and have long been used as traditional medicines with scientifically proven pharmacological benefits. They serve vast-ranging medicinal activities that may lead drug discovery with novel and potential therapeutic evidence. Latest research magnifies primarily functional activity of flavonoids as antioxidant against oxidative stress. This review enlightens the prospective role of flavonoids as antioxidant.

  10. Antioxidants in Translational Medicine.

    Science.gov (United States)

    Schmidt, Harald H H W; Stocker, Roland; Vollbracht, Claudia; Paulsen, Gøran; Riley, Dennis; Daiber, Andreas; Cuadrado, Antonio

    2015-11-10

    It is generally accepted that reactive oxygen species (ROS) scavenging molecules or antioxidants exert health-promoting effects and thus their consumption as food additives and nutraceuticals has been greatly encouraged. Antioxidants may be beneficial in situations of subclinical deficiency and increased demand or acutely upon high-dose infusion. However, to date, there is little clinical evidence for the long-term benefit of most antioxidants. Alarmingly, recent evidence points even to health risks, in particular for supplements of lipophilic antioxidants. The biological impact of ROS depends not only on their quantities but also on their chemical nature, (sub)cellular and tissue location, and the rates of their formation and degradation. Moreover, ROS serve important physiological functions; thus, inappropriate removal of ROS may cause paradoxical reductive stress and thereby induce or promote disease. Any recommendation on antioxidants must be based on solid clinical evidence and patient-relevant outcomes rather than surrogate parameters. Such evidence-based use may include site-directed application, time-limited high dosing, (functional) pharmacological repair of oxidized biomolecules, and triggers of endogenous antioxidant response systems. Ideally, these approaches need guidance by patient stratification through predictive biomarkers and possibly imaging modalities.

  11. Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination.

    Science.gov (United States)

    Ono, Taisuke; Takada, Shingo; Kinugawa, Shintaro; Tsutsui, Hiroyuki

    2015-09-01

    What is the central question of this study? We sought to examine whether curcumin could ameliorate skeletal muscle atrophy in diabetic mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. What is the main finding and its importance? We found that curcumin ameliorated skeletal muscle atrophy in streptozotocin-induced diabetic mice by inhibiting protein ubiquitination without affecting protein synthesis. This favourable effect of curcumin was possibly due to the inhibition of inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 diabetes mellitus. Skeletal muscle atrophy develops in patients with diabetes mellitus (DM), especially in type 1 DM, which is associated with chronic inflammation. Curcumin, the active ingredient of turmeric, has various biological actions, including anti-inflammatory and antioxidant properties. We hypothesized that curcumin could ameliorate skeletal muscle atrophy in mice with streptozotocin-induced type 1 DM. C57BL/6 J mice were injected with streptozotocin (200 mg kg(-1) i.p.; DM group) or vehicle (control group). Each group of mice was randomly subdivided into two groups of 10 mice each and fed a diet with or without curcumin (1500 mg kg(-1) day(-1)) for 2 weeks. There were significant decreases in body weight, skeletal muscle weight and cellular cross-sectional area of the skeletal muscle in DM mice compared with control mice, and these changes were significantly attenuated in DM+Curcumin mice without affecting plasma glucose and insulin concentrations. Ubiquitination of protein was increased in skeletal muscle from DM mice and decreased in DM+Curcumin mice. Gene expressions of muscle-specific ubiquitin E3 ligase atrogin-1/MAFbx and MuRF1 were increased in DM and inhibited in DM+Curcumin mice. Moreover, nuclear factor-κB activation, concentrations of the inflammatory cytokines tumour necrosis factor-α and interleukin-1β and oxidative

  12. Sesamin Ameliorates Advanced Glycation End Products-Induced Pancreatic β-Cell Dysfunction and Apoptosis

    Directory of Open Access Journals (Sweden)

    Xiang Kong

    2015-06-01

    Full Text Available Advanced glycation end products (AGEs, the direct modulators of β-cells, have been shown to cause insulin-producing β-cell dysfunction and apoptosis through increase of intracellular reactive oxygen species (ROS production. Sesamin has been demonstrated to possess antioxidative activity. This study was designed to investigate whether sesamin protects against AGEs-evoked β-cell damage via its antioxidant property. The effects of sesamin were examined in C57BL/6J mice and MIN6 cell line. In in vivo studies, mice were intraperitoneally injected with AGEs (120 mg/kg and orally treated with sesamin (160 mg/kg for four weeks. Intraperitoneal glucose tolerance and insulin releasing tests were performed. Insulin content, ROS generation and β-cell apoptosis in pancreatic islets were also measured. In in vitro studies, MIN6 cells were pretreated with sesamin (50 or 100 μM and then exposed to AGEs (200 mg/L for 24 h. Insulin secretion, β-cell death, ROS production as well as expression and activity of NADPH oxidase were determined. Sesamin treatment obviously ameliorated AGE-induced β-cell dysfunction and apoptosis both in vivo and in vitro. These effects were associated with decreased ROS production, down-regulated expression of p67phox and p22phox, and reduced NADPH oxidase activity. These results suggest that sesamin protects β-cells from damage caused by AGEs through suppressing NADPH oxidase-mediated oxidative stress.

  13. Using of Coffee and Cardamom Mixture to Ameliorate Oxidative Stress Induced in irradiated Rats

    International Nuclear Information System (INIS)

    Hamza, R.G.; Osman, N.N.

    2013-01-01

    Human exposure to ionizing radiation induced overproduction of free radicals leading to oxidative stress. This study aimed to evaluate the possibility of using of coffee and cardamom mixture; as natural antioxidant compounds ; to ameliorate oxidative stress in rats induced by exposure to ionizing radiation. Phenolic contents in coffee and essential oils in cardamom were identified by using HPLC chromatography and GC/MS analysis. Four groups of adult male rats were used; the control group (A), the second group (B) received orally the mixture extract of coffee and cardamom (60 mg/100g body weight) for 8 weeks, the third group (C) irradiated (6 Gy) and the fourth group (D) received orally the mixture extract for 8 weeks and exposed to radiation at the 4th week. The results revealed that the administration of mixture extract of coffee and cardamom to rats significantly reduced the damage effect induced by irradiation via the adjustment of the antioxidant status, decreasing of malondialdehyde content and the subsequent amending of different biochemical parameters as well as some hormones. Accordingly, it is possible to indicate that coffee-cardamom reduced the radiation exposure induced oxidative stress.

  14. Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats.

    Science.gov (United States)

    Tahan, Veysel; Atug, Ozlen; Akin, Hakan; Eren, Fatih; Tahan, Gulgun; Tarcin, Ozlem; Uzun, Hafize; Ozdogan, Osman; Tarcin, Orhan; Imeryuz, Nese; Ozguner, Fehmi; Celikel, Cigdem; Avsar, Erol; Tozun, Nurdan

    2009-05-01

    Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti-inflammatory and anti-apoptotic agent. We aimed to evaluate the effects of melatonin on methionine- and choline-deficient diet (MCDD)-induced NASH in rats. Thirty-two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair-fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.'s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti-inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.

  15. Role of Antioxidants in Horse Serum-mediated Vasculitis in Swine: Potential Relevance to Early Treatment in Mitigation of Coronary Arteritis in Kawasaki Disease

    Directory of Open Access Journals (Sweden)

    Saji Philip

    2017-08-01

    Conclusion: Serum sickness is a prototype of immune complex vasculitis, and the severity can be ameliorated with antioxidants. A trial of therapeutic dosages of vitamins A, E, and C in acute phase of Kawasaki disease, may be effective in mitigation of coronary artery lesion in addition to intravenous immunoglobulin and aspirin.

  16. Food Processing Antioxidants.

    Science.gov (United States)

    Hidalgo, F J; Zamora, R

    Food processing has been carried out since ancient times as a way to preserve and improve food nutritional and organoleptic properties. Although it has some undesirable consequences, such as the losses of some nutrients and the potential formation of toxic compounds, a wide range of benefits can be enumerated. Among them, the increased total antioxidant capacity of many processed foods has been known for long. This consequence has been related to both the release or increased availability of natural antioxidants and the de novo formation of substances with antioxidant properties as a consequence of the produced reactions. This review analyzes the chemical changes produced in foods during processing with special emphasis on the formation of antioxidants as a consequence of carbonyl-amine reactions produced by both carbohydrate- and lipid-derived reactive carbonyls. It discusses the lastest advances produced in the characterization of carbonyl-amine adducts and their potential action as primary (free radical scavengers), secondary (chelating and other ways to prevent lipid oxidation), and tertiary (carbonyl scavengers as a way to avoid lipid oxidation consequences) antioxidants. Moreover, the possibility of combining amino compounds with different hydrophobicity, such as aminophospholipids and proteins, with a wide array of reactive carbonyls points out to the use of carbonyl-amine reactions as a new way to induce the formation of a great variety of substances with antioxidant properties and very variable hydrophilia/lipophilia. All presented results point out to carbonyl-amine reactions as an effective method to generate efficacious antioxidants that can be used in food technology. © 2017 Elsevier Inc. All rights reserved.

  17. Improvement for Amelioration Inventory Model with Weibull Distribution

    Directory of Open Access Journals (Sweden)

    Han-Wen Tuan

    2017-01-01

    Full Text Available Most inventory models dealt with deteriorated items. On the contrary, just a few papers considered inventory systems under amelioration environment. We study an amelioration inventory model with Weibull distribution. However, there are some questionable results in the amelioration paper. We will first point out those questionable results in the previous paper that did not derive the optimal solution and then provide some improvements. We will provide a rigorous analytical work for different cases dependent on the size of the shape parameter. We present a detailed numerical example for different ranges of the sharp parameter to illustrate that our solution method attains the optimal solution. We developed a new amelioration model and then provided a detailed analyzed procedure to find the optimal solution. Our findings will help researchers develop their new inventory models.

  18. Riboflavin ameliorates cisplatin induced toxicities under photoillumination.

    Directory of Open Access Journals (Sweden)

    Iftekhar Hassan

    Full Text Available BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

  19. Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

    Science.gov (United States)

    Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

    2017-02-01

    Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

  20. Antioxidant and Antioxidant capacity of raw and processed Nigerian ...

    African Journals Online (AJOL)

    Lechner,2010;. Zhang et al., 2013) and hepatoprotective effects. (Rabeh, 2015). This study was carried out to investigate the antioxidant and antioxidant capacity of raw and processed Nigerian red Beetroots for its potential as a functional food.

  1. Changes in the oxidative stress/anti-oxidant system after exposure to sulfur mustard and antioxidant strategies in the therapy, a review.

    Science.gov (United States)

    Pohanka, Miroslav; Martinkova, Pavla; Brtnicky, Martin; Kynicky, Jindrich

    2017-07-01

    Sulfur mustard, in a chemical name bis(2-chloroethyl) sulfide, is a chemical warfare agent. It is cytotoxic and blister forming once spread over the skin. Though exact molecular mechanism of sulfur mustard toxic action remains unknown, inflammation and oxidative stress development are considered as the most relevant pathological consequences. Applications of either low-molecular weight antioxidants or cofactors for enzymatic antioxidants are considered as suitable ways how to ameliorate the poisoning. In this article, survey of literature on countermeasures against sulfur mustard poisoning are given and evidence of oxidative stress role during sulfur mustard poisoning and availability of antioxidants for the therapy are discussed.

  2. Timing of antioxidant supplementation is critical in improving anorexia in an experimental model of cancer.

    Science.gov (United States)

    Molfino, Alessio; De Luca, Simona; Muscaritoli, Maurizio; Citro, Gennaro; Fazi, Lucia; Mari, Alessia; Ramaccini, Cesarina; Rossi Fanelli, Filippo; Laviano, Alessandro

    2013-08-01

    Increased oxidative stress may contribute to cancer anorexia, which could be ameliorated by antioxidant supplementation. methylcholanthrene (MCA) sarcoma-bearing Fisher rats were studied. After tumour inoculation, rats were randomly assigned to standard diet (CTR group, n = 6), or to an antioxidant-enriched diet (AOX group, n = 8). Eight more rats (STD-AOX group) switched from standard to antioxidant diet when anorexia developed. At the end of the study, food intake (FI, g/d), body weight and tumour weight (g) were recorded, and plasma samples were obtained. On day 16, anorexia has appeared only in CTR and STD-AOX animals. At the end of the study, FI in AOX animals was still higher than in the other groups (p = 0.08). No differences in body and tumour weights were observed among groups. However, hydrogen peroxide and interleukin-1β levels were significantly reduced only in AOX rats. Data obtained suggest that early antioxidant supplementation improves cancer anorexia, ameliorates oxidative stress and reduces inflammation.

  3. Antioxidants and vascular health.

    Science.gov (United States)

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  4. Oral thymoquinone administration ameliorates: the effect of cisplatin on brush border membrane enzymes, energy metabolism, and redox status in rat kidney.

    Science.gov (United States)

    Farooqui, Zeba; Shahid, Faaiza; Abidi, Subuhi; Parwez, Iqbal; Khan, Farah

    2017-12-01

    Therapeutic use of cisplatin (CP), an effective anticancer drug, is limited by dose dependent nephrotoxicity. Thymoquinone (TQ), the major Nigella sativa seed oil constituent has been shown to prevent progression of various renal disorders. The present study investigates the protective effect of TQ on CP-induced nephrotoxicity. Rats were divided into six groups viz. control, CP, CPTQ 1 , CPTQ 2 , CPTQ 3 , and TQ alone group. Animals in CP and TQ combination groups were administered TQ (0.5, 1.5, and 3 mg/kg bwt, orally) with single intraperitoneal dose of CP (6 mg/kg bwt). The effect of TQ administration was determined on CP-induced alterations in various serum/urine parameters and on the enzymes of brush border membrane enzyme (BBM), carbohydrate metabolism, and antioxidant defense system in renal cortex and medulla. Oral administration of TQ in all the three doses prior to and following a single dose CP treatment caused significant recovery of serum creatinine and blood urea nitrogen levels; however, maximum recovery was seen in CPTQ 2 group. TQ administration averted CP-induced decline in BBM activities, both in the cortical and medullary homogenates and in isolated BBM vesicles. TQ administration also ameliorated CP-induced impairments in renal metabolic and antioxidant status. Histopathological studies supported these biochemical findings. TQ ameliorates CP-induced oxidative damage owing to its intrinsic antioxidant properties.

  5. Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage

    NARCIS (Netherlands)

    Gonzalez Ponce, Herson Antonio; Consolacion Martinez-Saldana, Maria; Rosa Rincon-Sanchez, Ana; Teresa Sumaya-Martinez, Maria; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han; Jaramillo-Juarez, Fernando

    2016-01-01

    Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-L-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients

  6. Regulatory mechanisms of viral hepatitis B and C

    Indian Academy of Sciences (India)

    Unknown

    hepatitis C virus; IFN, interferon; IRES, internal ribosome entry site; NAC, N-acetyl L-cysteine; NLS, nuclear localization signal;. NS5A, nonstructural protein 5A; PDTC, pyrrolidine dithiocarbamate; PKR, double stranded RNA-dependent protein kinase; ROS, reactive oxygen species; RR, ruthenium red; UPR, unfolded protein ...

  7. Antioxidants for female subfertility.

    Science.gov (United States)

    Showell, Marian G; Mackenzie-Proctor, Rebecca; Jordan, Vanessa; Hart, Roger J

    2017-07-28

    A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility. To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women. We searched the following databases (from their inception to September 2016) with no language or date restriction: Cochrane Gynaecology and Fertility Group (CGFG) specialised register, the Cochrane Central Register of Studies (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of appropriate studies and searched for ongoing trials in the clinical trials registers. We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility. Two review authors independently selected eligible studies, extracted the data and assessed the risk of bias of the included studies. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events. We pooled studies using a fixed-effect model, and calculated odds ratios (ORs) with 95% confidence intervals (CIs) for the dichotomous

  8. Physical performance and antioxidant effects in triathletes

    Directory of Open Access Journals (Sweden)

    M Dékány

    2008-06-01

    Full Text Available Exercise results in an increased production of reactive oxygen species. Two major classes of endogenous protective mechanisms work together to ameliorate the harmful effects of oxidants in the cell: (1 components of the enzymatic scavenging system such as superoxide dismutase, glutathione-peroxidase and catalase and (2 nonenzymatic antioxidants. The purpose of this study was to identify any relationship between duration and intensity of prolonged physical exercise and markers of oxidative stress with the primary antioxidant system. Eleven triathletes performed a field test, which consisted of 1.9 km swimming, 60 km cycling and 21 km running. Venous and arterialized blood enzymatic activities of SOD, CAT, GPX, and creatine kinase and concentrations of glucose, lactate, malondialdehyde and bilirubin were determined. Athletes were divided into two groups: the more efficient group (A, and the less efficient group (B, according to their duration of the field test. The activity of GPX was significantly higher in Group A than Group B, irrespective of the duration of the exercise, but bilirubin concentration was lower. For Group B, SOD activity increased during running while CAT activity decreased after cycling and after running. Upon completion of the test, CK activity was elevated in both groups. The free radical scavenging system appears to be directly related to individiual physiological efficiency with prolonged submaximal physical exercise. According to our estimation of the individual training status and the adequate adaptation level, it is important to take into consideration the markers of free radical production and the activities of the scavenging compounds. Abbreviations: SOD - superoxide dismutase, GPX - glutathione peroxidase, CAT - catalase, MDA - malondialdehyde, CK - creatine kinase.

  9. PHYTOCHEMICAL ANALYSIS, ANTIOXIDANT AND ...

    African Journals Online (AJOL)

    2012-12-31

    EC50 in μg/ml) and total antioxidant activity (mg GAE/g DW) power Phoenyx dactylifera leaves extract and anthentic standards (BHT in IC50, BHA and chlorogenic acid in EC50 μg/ml). Plant species and standards. DPPH test.

  10. Antioxidants: real medicines?

    African Journals Online (AJOL)

    Repro

    While endogenous metabolic pathways utilise oxidative processes largely for our benefit, various pathological .... quenchers of these oxidants have been discovered and characterised. Endogenous antioxidants may be ... ly recognised, what is much less well known is the fact that vitamin. E is a family of 8 vitamins: 4 toco-.

  11. Antioxidant effects of carotenoids

    NARCIS (Netherlands)

    Bast, A.; Haenen, G.R.M.M.; Berg, R. van den; Berg, H. van den

    1998-01-01

    Surprisingly, neither the precise pharmacological effect nor the toxicological profile is usually established for food components. Carotenoids are no exception in this regard. Only limited insight into the pharmacology and toxicology of carotenoids exists. It is known that the antioxidant action of

  12. Arbuscular mycorrhizal symbiosis modulates antioxidant response in salt-stressed Trigonella foenum-graecum plants.

    Science.gov (United States)

    Evelin, Heikham; Kapoor, Rupam

    2014-04-01

    An experiment was conducted to evaluate the influence of Glomus intraradices colonization on the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), peroxidase (PX), ascorbate peroxidase (APX), and glutathione reductase (GR)] and the accumulation of nonenzymatic antioxidants (ascorbic acid, α-tocopherol, glutathione, and carotenoids) in roots and leaves of fenugreek plants subjected to varying degrees of salinity (0, 50, 100, and 200 mM NaCl) at two time intervals (1 and 14 days after saline treatment, DAT). The antioxidative capacity was correlated with oxidative damage in the same tissue. Under salt stress, lipid peroxidation and H2O2 concentration increased with increasing severity and duration of salt stress (DoS). However, the extent of oxidative damage in mycorrhizal plants was less compared to nonmycorrhizal plants. The study reveals that mycorrhiza-mediated attenuation of oxidative stress in fenugreek plants is due to enhanced activity of antioxidant enzymes and higher concentrations of antioxidant molecules. However, the significant effect of G. intraradices colonization on individual antioxidant molecules and enzymes varied with plant tissue, salinity level, and DoS. The significant effect of G. intraradices colonization on antioxidative enzymes was more evident at 1DAT in both leaves and roots, while the concentrations of antioxidant molecules were significantly influenced at 14DAT. It is proposed that AM symbiosis can improve antioxidative defense systems of plants through higher SOD activity in M plants, facilitating rapid dismutation of O2 (-) to H2O2, and subsequent prevention of H2O2 build-up by higher activities of CAT, APX, and PX. The potential of G. intraradices to ameliorate oxidative stress generated in fenugreek plants by salinity was more evident at higher intensities of salt stress.

  13. GARLIC AMELIORATES THE HEPATOTOXIC EFFECT INDUCED BY THIOACETAMIDE IN FEMALE RATS

    International Nuclear Information System (INIS)

    OSMAN, H.F.; TAHA, M.S.

    2008-01-01

    The purpose of this study was to investigate the pretreatment effect of garlic on hepatotoxicity and oxidative stress induced by thioacetamide (TAA) in female albino rats.Sixty female adult albino rats were assigned equally into four groups; control group: animals without treatment, group ?: rats given daily oral dose of 250 mg/ kg garlic for 28 days, group ??: rats injected intraperitonealy by thioacetamide 20 mg ? kg for two weeks and group III: rats given 250 mg / kg garlic orally for 28 day followed by intrapertoneal injection of 20 mg / kg thioacetamide for two weeks. Liver enzymes were evaluated by measurements of AST, ALT and alkaline phosphatase and also trace elements (Cu and Zn) were estimated. Superoxide dismutase, glutathione peroxidase, malondialdehyde and thyroid hormones (T3 and T4) were assessed. Also, histological studies on liver and stomach were carried out. The results indicated that treatment with garlic significantly decreased liver enzymes (AST, ALT and ALP). Cu showed high significant increase in groups treated with garlic and also garlic + TAA, while Zn was increased significantly in TAA group. Superoxide dismutase (SOD) was increased significantly in group I while TAA decreased it significantly. Glutathione peroxidase was decreased significantly in group II while its level in group IV reached near the control value. Similarly, malondialdehyde was decreased significantly in garlic group and garlic ameliorated the thioacetamide effect in garlic + TAA group. The treatment with TAA led to significant increase in T3 and significant decrease in T4 hormones. Garlic ameliorated T3 level to reach the control level. Histologically, pre-treatment with garlic induced a prophylactic activity against the thioacetamide in liver and stomach tissues.According to the obtained results, it could be conclude that garlic treatment may act as antioxidant or pro-oxidant in TAA treated animals besides decreasing the TAA toxic effects on liver enzymes, liver and

  14. Whole cell Deinococcus radiodurans ameliorates salt stress in Indian mustard through pyrroloquinoline quinone

    International Nuclear Information System (INIS)

    Srivastava, A.K.; Jadhav, P.; Suprasanna, P.; Rajpurohit, Y.S.; Misra, H.S.

    2015-01-01

    Salinity stress is considered as one of the major abiotic stresses limiting crop productivity. A variety of symbiotic and non-symbiotic bacteria are currently being used worldwide with the aim to boost built-in defense system in plants. Deinococcus radiodurans is a highly desiccation and radiation tolerant bacterium which synthesizes PQQ (pyrroloquinoline quinone) that has been shown to have a versatile role in crop productivity and as a general stress response regulator in bacteria and mammals. PQQ also acts as scavenger of reactive oxygen species and hence, can module redox signaling, one of the major regulator of stress tolerance in plants. In view of this, present research was conducted to evaluate the potential of whole cell D. radiodurans for ameliorating salt stress in plants. The soil colonization with wild-type cells led to partial amelioration of salt stress. The PQQ mutant showed an intermediate phenotype between wild-type seedlings and those grown on non-colonized soils which confirmed that the effects are largely associated with PQQ. The differential phenotype was also correlated with ROS level and ABA accumulation. The flame photometry data showed that there was no significant reduction in water soluble Na + level in control plant and those treated with either wild-type or PQQ mutant. Further, the elevated levels of antioxidant enzymes and reduced ascorbate in the plants treated with bacterial cells indicated its positive role in oxidative stress management. Although, the exact molecular basis to these effects is yet to be understood, present findings support the use of whole cell D. radiodurans for managing the growth and productivity of Indian mustard in salt affected fields. (author)

  15. Nigella sativa oil Ameliorates ionizing Radiation induced cellular injury in Male Albino Rats

    International Nuclear Information System (INIS)

    Mohamed, E.T.; El-Kady, A.A.

    2013-01-01

    Nigella sativa (NS), commonly known as black seed, is a plant spices in which thymoquinone is the main active ingredient isolated from the black seeds. The seeds of Nigella sativa are used in herbal medicine all over the world for the treatment and prevention of a number of diseases. The aim of this study was focused on investigating the possible protective effect of NS against gamma radiation induced nephrotoxicity and inflammatory changes in male albino rats. Twenty four albino rats were divided into four equal groups as follows: control group, irradiated group (animals subjected to whole body gamma irradiation at a dose of 6 Gy), treated group (rats treated with 0.2 ml/kg, i.p., NS oil for 4 weeks), and treated irradiated group (animals treated with 0.2 mL/kg, i.p., NS oil for 4 weeks then exposed to whole body gamma irradiation at a dose of 6 Gy). The obtained results revealed that the administration of Nigella sativa oil to irradiated rats significantly ameliorated the changes induced in kidney antioxidant system; catalase and glutathione peroxidase activities as well as reduced glutathione concentration. Also, NS oil restored the kidney function indices (urea and creatinine) near normal level when compared with their equivalent values in irradiated rats. In addition, the changes in serum tumor necrosis factor alpha (TNF-α), Interleukin-1β (IL-1β) and Interleukin-6 (IL-6) activities were markedly improved compared to the corresponding values of irradiated group. The histopathological results showed distinctive pattern of ischemic renal injury in irradiated group, while in treated- irradiated group the renal tissues showed relatively well-preserved architecture with or without focal degeneration. In conclusion, NS acts in the kidney as a potent scavenger of free radicals to prevent or ameliorates the toxic effects of gamma irradiation as shown in the biochemical and histopathological study and also NS oil might provide substantial protection against

  16. MAPK/JNK1 activation protects cells against cadmium-induced autophagic cell death via differential regulation of catalase and heme oxygenase-1 in oral cancer cells.

    Science.gov (United States)

    So, Keum-Young; Kim, Sang-Hun; Jung, Ki-Tae; Lee, Hyun-Young; Oh, Seon-Hee

    2017-10-01

    Antioxidant enzymes are related to oral diseases. We investigated the roles of heme oxygenase-1 (HO-1) and catalase in cadmium (Cd)-induced oxidative stress and the underlying molecular mechanism in oral cancer cells. Exposing YD8 cells to Cd reduced the expression levels of catalase and superoxide dismutase 1/2 and induced the expression of HO-1 as well as autophagy and apoptosis, which were reversed by N-acetyl-l-cysteine (NAC). Cd-exposed YD10B cells exhibited milder effects than YD8 cells, indicating that Cd sensitivity is associated with antioxidant enzymes and autophagy. Autophagy inhibition via pharmacologic and genetic modulations enhanced Cd-induced HO-1 expression, caspase-3 cleavage, and the production of reactive oxygen species (ROS). Ho-1 knockdown increased autophagy and apoptosis. Hemin treatment partially suppressed Cd-induced ROS production and apoptosis, but enhanced autophagy and CHOP expression, indicating that autophagy induction is associated with cellular stress. Catalase inhibition by pharmacological and genetic modulations increased Cd-induced ROS production, autophagy, and apoptosis, but suppressed HO-1, indicating that catalase is required for HO-1 induction. p38 inhibition upregulated Cd-induced phospho-JNK and catalase, but suppressed HO-1, autophagy, apoptosis. JNK suppression exhibited contrary results, enhancing the expression of phospho-p38. Co-suppression of p38 and JNK1 failed to upregulate catalase and procaspase-3, which were upregulated by JNK1 overexpression. Overall, the balance between the responses of p38 and JNK activation to Cd appears to have an important role in maintaining cellular homeostasis via the regulation of antioxidant enzymes and autophagy induction. In addition, the upregulation of catalase by JNK1 activation can play a critical role in cell protection against Cd-induced oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-01-01

    Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections.Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops.The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

  18. Bis-butanediol-mercapturic acid (bis-BDMA) as a urinary biomarker of metabolic activation of butadiene to its ultimate carcinogenic species

    Science.gov (United States)

    Tretyakova, Natalia Y.

    2014-01-01

    Human carcinogen 1,3-butadiene (BD) undergoes metabolic activation to 3,4-epoxy-1-butene (EB), hydroxymethylvinyl ketone (HMVK), 3,4-epoxy-1,2-butanediol (EBD) and 1,2,3,4-diepoxybutane (DEB). Among these, DEB is by far the most genotoxic metabolite and is considered the ultimate carcinogenic species of BD. We have shown previously that BD-exposed laboratory mice form 8- to 10-fold more DEB–DNA adducts than rats exposed at the same conditions, which may be responsible for the enhanced sensitivity of mice to BD-mediated cancer. In the present study, we have identified 1,4-bis-(N-acetyl-l-cystein-S-yl)butane-2,3-diol (bis-BDMA) as a novel DEB-specific urinary biomarker. Isotope dilution high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was employed to quantify bis-BDMA and three other BD-mercapturic acids, 2-(N-acetyl-l-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-l-cystein-S-yl)-2-hydroxy-but-3-ene (MHBMA, from EB), 4-(N-acetyl-l-cystein-S-yl)-1,2-dihydroxybutane (DHBMA, from HMVK) and 4-(N-acetyl-l-cystein-S-yl)-1,2,3-trihydroxybutane (THBMA, from EBD), in urine of confirmed smokers, occupationally exposed workers and BD-exposed laboratory rats. Bis-BDMA was formed in a dose-dependent manner in urine of rats exposed to 0–200 p.p.m. BD by inhalation, although it was a minor metabolite (1%) as compared with DHBMA (47%) and THBMA (37%). In humans, DHBMA was the most abundant BD-mercapturic acid excreted (93%), followed by THBMA (5%) and MHBMA (2%), whereas no bis-BDMA was detected. These results reveal significant differences in metabolism of BD between rats and humans. PMID:24531806

  19. "Lycopene: A Promising Antioxidant"

    Directory of Open Access Journals (Sweden)

    Anshumalee Nisheeth

    2007-01-01

    Full Text Available Lycopene is a red colored fat soluble carotenoid, which gives tomatoes and several other fruits their deep red colour. It has shown potential role in prevention and cure of various systemic and oral diseases including malignancies due to its antioxidant and other cancer preventing properties. Lycopene with its 11 conjugated and 2 non conjugated double bonds is the most efficient singIet oxygen quencher and is considered most potent antioxidant among carotenoids. It has shown to be efficient in the management of oral cancer and precancer like leukoplakia and has shown the potential in the management of other oral mucosal lesions thought to arise due to free radical onslaught such as oral lichen planes.

  20. Antioxidants in dermatology*

    Science.gov (United States)

    Addor, Flavia Alvim Sant'anna

    2017-01-01

    The skin cells continuously produce, through cellular respiration, metabolic processes or under external aggressions, highly reactive molecules oxidation products, generally called free radicals. These molecules are immediately neutralized by enzymatic and non-enzymatic systems in a physiological and dynamic balance. In situations where this balance is broken, various cellular structures, such as the cell membrane, nuclear or mitochondrial DNA may suffer structural modifications, triggering or worsening skin diseases. several substances with alleged antioxidant effects has been offered for topical or oral use, but little is known about their safety, possible associations and especially their mechanism of action. The management of topical and oral antioxidants can help dermatologist to intervene in the oxidative processes safely and effectively, since they know the mechanisms, limitations and potential risks of using these molecules as well as the potential benefits of available associations. PMID:29186248

  1. Rutin and quercetin show greater efficacy than nifedipin in ameliorating hemodynamic, redox, and metabolite imbalances in sodium chloride-induced hypertensive rats.

    Science.gov (United States)

    Olaleye, M T; Crown, O O; Akinmoladun, A C; Akindahunsi, A A

    2014-06-01

    Rutin and quercetin were investigated for their effects on blood pressure and antioxidant defense system of rats fed with 8% sodium chloride-supplemented diet (high salt diet) for 6 weeks. Animals fed with high salt diet demonstrated an increase in systolic, diastolic, pulse, and mean arterial blood pressures (p high salt diet but not post-treated. The high salt diet also led to significant increase in serum glucose, urea, creatinine, triglycerides, low-density-lipoprotein, and total cholesterol concentrations. Treatment with rutin and quercetin ameliorated the effects of high salt diet on these biochemical indices. The reference standard, nifedipin was less effective than rutin and quercetin. The results of this study highlight the risk of high salt consumption on cardiovascular health and the potent antioxidant and antihypertensive property of rutin and quercetin. © The Author(s) 2014.

  2. Andrographolide Ameliorates Beta-Naphthoflavone-Induced CYP1A Enzyme Activity and Lipid Peroxidation in Hamsters with Acute Opisthorchiasis.

    Science.gov (United States)

    Udomsuk, Latiporn; Chatuphonprasert, Waranya; Jarukamjorn, Kanokwan; Sithithaworn, Paiboon

    2016-01-01

    Opisthorchis viverrini (OV) infection generates oxidative stress/free radicals and is considered as a primary cause ofcholangiocarcinoma since it primarily triggers sclerosing cholangitis. In this study, the impacts of andrographolide on acute opisthorchaisis in β-naphthoflavone (BNF)-exposed hamsters were investigated. Ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities and Thiobarbituric acid reaction substances (TBARS) assay of andrographolide in acute opisthorchiasis in the BNF-exposed hamsters were assessed. The results showed that andrographolide ameliorated the hepatic CYP1A1 and CYP1A2 activities by decreases of the specific enzymatic reactions of EROD and MROD, respectively, in the BNF-exposed hamsters. Moreover, andrographolide lowered the formation of malondialdehyde in the livers and brains of the hamsters. These observations revealed the promising chemo-protective and antioxidant activities of andrographolide via suppression of the specific EROD and MROD reactions and lipid peroxidation against acute opisthorchiasis in the BNF-exposed hamsters.

  3. Thymoquinone ameliorates lead-induced suppression of the ...

    African Journals Online (AJOL)

    Objective: Alteration of the antioxidant status in the kidneys may be related to lead (Pb) intoxication. The present study aimed to investigate the possible beneficial effect of thymoquinone (TQ), the major active ingredient of the volatile oil of Nigella sativa seeds, on Pb-induced renal antioxidant defense system impairment.

  4. Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse

    Science.gov (United States)

    Kumari, Mrinalini; Singh, Poonam

    2015-01-01

    Objective: The present study was undertaken to evaluate the protective effects of the fruit extract of Tribulus terrestris (TT) on the metronidazole (MTZ)-induced alterations in spermatogenesis, sperm count, testicular functions, and oxidative stress. Materials and Methods: Thirty adult Swiss strain mice were divided into six groups. Animals of Groups I and II served as untreated and vehicle-treated controls, while that of Groups III and IV were administered with MTZ (500 mg/kg BW/day) and TT (200 mg/kg BW/day) alone for 28 days, respectively. Low (100 mg/kg BW/day) and high (200 mg/kg BW/day) doses of TT along with MTZ (500 mg/kg BW/day) were administered for 28 days in the mice of Groups V and VI, respectively. Twenty four hours after the last treatment, all the animals were euthanized to study the histological changes in the testis and sperm count in the epididymis. Testicular functional markers, lipid peroxidation (LPO) and the activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were also assessed in the mice of all the groups. Results: Metronidazole caused marked alterations in the testicular weight, spermatogenesis, activities of antioxidant enzymes, lactate dehydrogenase, alkaline phosphatase, and the level of LPO. The epididymal sperm count also declined significantly in MTZ-treated group. These changes were partially restored following co-administration of 500 mg/kg BW/day of MTZ and 100 mg/kg BW/day of TT. However, in the mice co-administered with 500 mg/kg BW/day of MTZ and 200 mg/kg BW/day of TT, the changes reverted back completely, similar to that of the controls. Conclusion: The fruit extract of TT ameliorates the MTZ-induced alterations in the testis. PMID:26069369

  5. Physiological integration ameliorates negative effects of drought stress in the clonal herb Fragaria orientalis.

    Directory of Open Access Journals (Sweden)

    Yunchun Zhang

    Full Text Available Clonal growth allows plants to spread horizontally and to establish ramets in sites of contrasting resource status. If ramets remain physiologically integrated, clones in heterogeneous environments can act as cooperative systems--effects of stress on one ramet can be ameliorated by another connected ramet inhabiting benign conditions. But little is known about the effects of patch contrast on physiological integration of clonal plants and no study has addressed its effects on physiological traits like osmolytes, reactive oxygen intermediates and antioxidant enzymes. We examined the effect of physiological integration on survival, growth and stress indicators such as osmolytes, reactive oxygen intermediates (ROIs and antioxidant enzymes in a clonal plant, Fragaria orientalis, growing in homogenous and heterogeneous environments differing in patch contrast of water availability (1 homogeneous (no contrast group; 2 low contrast group; 3 high contrast group. Drought stress markedly reduced the survival and growth of the severed ramets of F. orientalis, especially in high contrast treatments. Support from a ramet growing in benign patch considerably reduced drought stress and enhanced growth of ramets in dry patches. The larger the contrast between water availability, the larger the amount of support the depending ramet received from the supporting one. This support strongly affected the growth of the supporting ramet, but not to an extent to cause increase in stress indicators. We also found indication of costs related to maintenance of physiological connection between ramets. Thus, the net benefit of physiological integration depends on the environment and integration between ramets of F. orientalis could be advantageous only in heterogeneous conditions with a high contrast.

  6. Ameliorative Effect of Arctium lappa Against Cadmium Genotoxicity and Histopathology in Kidney of Wistar Rat.

    Science.gov (United States)

    Suliman Al-Gebaly, Asma

    2017-01-01

    Cadmium (Cd) is a non-essential metal whose dispersion in the environment has increased recently, Cd may enhance cell oxidative stress that leads to DNA damage and apoptotic cell death. The study aimed to evaluate the antioxidative capability of Burdock root 'Arctium lappa' on cadmium-induced oxidative stress and histopathology of the kidney of Wistar rats. Cadmium was applied in a form of cadmium chloride to three groups (15 mg Cd kg-1) for five weeks with two groups pre-treated with 'Arctium lappa' administration, 100 and 200 mg kg-1 b.wt. Data were analyzed using one way analysis of variance (ANOVA) followed by Least Significant Difference (LSD) test to determine the difference among means using the JMP version 12. Results revealed that cadmium induced a significant disorganization (pArctium lappa kg-1 b.wt., showed a slightly less hypercellularity of glomerulus and reduction in the cell tail (59 μm). Furthermore, histological sections of kidney of rats pre-treated with 200 mg Arctium lappa kg-1 b.wt., showed high improvement of renal tubules and glomerulus with a prominent urinary space beside tail length of cells was recorded as 39 μm which was lower in comparison to other groups. Moreover, cadmium induced cellular destruction of the kidney was resumed with the pre-treatment of the secondary metabolites as an antioxidant compounds that produced from plant extracts. Arctium lappa leaf extract was efficient at both applied doses while 200 mg Arctium lappa kg-1 b.wt., had the most ameliorative effect.

  7. Ameliorative effects of rutin against metabolic, biochemical and hormonal disturbances in polycystic ovary syndrome in rats.

    Science.gov (United States)

    Jahan, Sarwat; Munir, Faryal; Razak, Suhail; Mehboob, Anam; Ain, Qurat Ul; Ullah, Hizb; Afsar, Tayyaba; Shaheen, Ghazala; Almajwal, Ali

    2016-12-07

    Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. The study was commenced to assess the favorable effects of Rutin against metabolic, biochemical, histological, and androgenic aspects of polycystic ovary syndrome in rats. Female Sprague-Dawley rats were administered letrozole (1 mg/kg) per orally (p.o) for a period of 21 days for the induction of PCOS, followed by dose of rutin (100 mg/kg and 150 mg/kg, p.o) for 15 days using 0.5% w/v CMC as vehicle. Metformin was also given as a standard control to one of the rat groups. Serum estradiol, progesterone, testosterone, serum lipid parameters, CRP and glucose levels were evaluated. Furthermore, antioxidant activity was tested using superoxide dismutase, catalase, glutathione per-oxidase and reactive-oxygen species level. Rutin flavonoid had a dose-dependent effect on androgenic levels depicting more recovery in the rutin-I treated group, while rutin-II treated groups showed better antioxidant and lipid profiles as compared with PCOS groups. A decrease in the value of C reactive protein (CRP) and a restoration in the proportion of estrous phase smears were observed in the rutin treated groups. Histopathological examination of ovary revealed a significant decrease in the number of cystic follicles in post treated groups. The effects observed with rutin were moderately similar to that with standard metformin, a widely used treatment drug for PCOS. The study provides evidence for the potential ameliorative effects of rutin against clinical and biochemical features of PCOS.

  8. Aronia melanocarpa Extract Ameliorates Hepatic Lipid Metabolism through PPARγ2 Downregulation.

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    Chung-Hwa Park

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a hepatic manifestation of metabolic syndrome. Studies have demonstrated that anthocyanin-rich foods may improve hyperlipidemia and ameliorate hepatic steatosis. Here, effects of Aronia melanocarpa (AM, known to be rich of anthocyanins, on hepatic lipid metabolism and adipogenic genes were determined. AM was treated to C57BL/6N mice fed with high fat diet (HFD or to FL83B cells treated with free fatty acid (FFA. Changes in levels of lipids, enzymes and hormones were observed, and expressions of adipogenic genes involved in hepatic lipid metabolism were detected by PCR, Western blotting and luciferase assay. In mice, AM significantly reduced the body and liver weight, lipid accumulation in the liver, and levels of biochemical markers such as fatty acid synthase, hepatic triglyceride and leptin. Serum transaminases, indicators for hepatocyte injury, were also suppressed, while superoxide dismutase activity and liver antioxidant capacity were significantly increased. In FL83B cells, AM significantly reduced FFA-induced lipid droplet accumulation. Protein synthesis of an adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 (PPARγ2 was inhibited in vivo. Furthermore, transcriptional activity of PPARγ2 was down-regulated in vitro, and mRNA expression of PPARγ2 and its downstream target genes, adipocyte protein 2 and lipoprotein lipase were down-regulated by AM both in vitro and in vivo. These results show beneficial effects of AM against hepatic lipid accumulation through the inhibition of PPARγ2 expression along with improvements in body weight, liver functions, lipid profiles and antioxidant capacity suggesting the potential therapeutic efficacy of AM on NAFLD.

  9. Amelioration of carbon tetrachloride-induced hepatic injury by emulsified Antrodia extract

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    Wei-Chih Chang

    2018-03-01

    Full Text Available Objective(s: Antrodia cinnamomea (AC is found with anti-inflammatory and immunomodulatory biological activities. In this study, we investigated the anti-hepatitis effect of the emulsified AC extract from RO water or supercritical fluid CO2 with ethanol co-solvent extract methods of AC preparations. Materials and Methods: Five groups of eight to ten weeks male rats with a count of ten for each group were studied to evaluate the protection of two kinds of AC extract from hepatic injury. Acute liver injury of rats was induced by injecting 40% carbon tetrachloride (CCl4 1 mg/kg intraperitoneally. Positive and negative control groups rats were perfused with CCl4 or isotonic saline, respectively. Experimental groups received oral administration once/day of AC preparations before CCl4 treatment: water AC extract (WAE group, or emulsified AC extract from supercritical fluid extraction (EAE group for 5 days, and sacrificed on the 6th day and the blood and liver samples were collected under chloral hydrate anesthesia. The anti-inflammatory, antioxidant markers, and relevant signaling pathways were measured (AST, ALT, ROS, IL-1, IL-6, NO, and COX-2, MAPKs, and caspase-3. Results: EAE at 50 mg/kg significantly decreased the serum AST, ALT, IL-1, IL-6, NO, and ROS levels. Both extracts reduced the activation of p-ERK in the liver samples, but EAE inhibited COX-2 and caspase-3 protein expression better than WAE. The EAE ameliorated CCl4-induced hepatic injury significantly; as compared with WAE and the positive control. Conclusion: The hepatoprotection of EAE could be attributed to the antioxidant and anti-inflammatory effects of Antrodia.

  10. Phoenix dactylifera seeds ameliorate early diabetic complications in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Abdelaziz, Dalia H A; Ali, Sahar A; Mostafa, Mahmoud M A

    2015-06-01

    In Arabic folk medicine, the seeds of Phoenix dactylifera L. (Arecaceae) have been used to manage diabetes for many years. Few studies have reported the antidiabetic effect of P. dactylifera seeds; however, their effect on diabetic complications is still unexplored. The present study investigates the protective effect of P. dactylifera seeds against diabetic complications in rats. The aqueous suspension of P. dactylifera seeds (aqPDS) (1 g/kg/d) was orally administered to streptozotocin-induced diabetic rats for 4 weeks. The serum biochemical parameters were assessed spectrophotometrically. Furthermore, oxidative stress was examined in both liver and kidney tissues by assessment of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), reduced glutathione, superoxide dismutase (SOD), glutathione S-transferase, and catalase. Oral administration of aqPDS significantly ameliorated the elevated levels of glucose (248 ± 42 versus 508 ± 60 mg/dl), urea (32 ± 3.3 versus 48.3 ± 5.6 mg/dl), creatinine (2.2 ± 0.35 versus 3.8 ± 0.37 mg/dl), ALT (29.6 ± 3.9 versus 46.4 ± 5.9 IU/l), and AST (73.3 ± 13 versus 127.8 ± 18.7 IU/l) compared with the untreated diabetic rats. In addition to significant augmentation in the activities of antioxidant enzymes, there was reduction in TBARS and NO levels and improvement of histopathological architecture of the liver and kidney of diabetic rats. The aqPDS showed potential protective effects against early diabetic complications of both liver and kidney. This effect may be explained by the antioxidant and free radical scavenging capabilities of P. dactylifera seeds.

  11. Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse.

    Science.gov (United States)

    Kumari, Mrinalini; Singh, Poonam

    2015-01-01

    The present study was undertaken to evaluate the protective effects of the fruit extract of Tribulus terrestris (TT) on the metronidazole (MTZ)-induced alterations in spermatogenesis, sperm count, testicular functions, and oxidative stress. Thirty adult Swiss strain mice were divided into six groups. Animals of Groups I and II served as untreated and vehicle-treated controls, while that of Groups III and IV were administered with MTZ (500 mg/kg BW/day) and TT (200 mg/kg BW/day) alone for 28 days, respectively. Low (100 mg/kg BW/day) and high (200 mg/kg BW/day) doses of TT along with MTZ (500 mg/kg BW/day) were administered for 28 days in the mice of Groups V and VI, respectively. Twenty four hours after the last treatment, all the animals were euthanized to study the histological changes in the testis and sperm count in the epididymis. Testicular functional markers, lipid peroxidation (LPO) and the activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were also assessed in the mice of all the groups. Metronidazole caused marked alterations in the testicular weight, spermatogenesis, activities of antioxidant enzymes, lactate dehydrogenase, alkaline phosphatase, and the level of LPO. The epididymal sperm count also declined significantly in MTZ-treated group. These changes were partially restored following co-administration of 500 mg/kg BW/day of MTZ and 100 mg/kg BW/day of TT. However, in the mice co-administered with 500 mg/kg BW/day of MTZ and 200 mg/kg BW/day of TT, the changes reverted back completely, similar to that of the controls. The fruit extract of TT ameliorates the MTZ-induced alterations in the testis.

  12. Study of ameliorating effects of ethanolic extract of Centella asiatica on learning and memory deficit in animal models.

    Science.gov (United States)

    Doknark, Saowalak; Mingmalairak, Salin; Vattanajun, Anusara; Tantisira, Boonyong; Tantisira, Mayuree H

    2014-02-01

    The present study investigated the effect of Centella asiatica ethanolic extract (CE) on learning and memoly imnpairment induced by either transient bilateral common carotid arteries occlusion (T2 VO) or an intraperitoneal injection of scopolamine in mice. CE (100, 300, 1000 or 1500 mg/kg, p.o.) were administered to learning and memory impaired mice once daily for 8 consecutive days. Learning and memory performance were evaluated by Morris water maze (MWM) and step-down passive avoidance (PA) test. Changes in malondialdehyde (MDA) levels in the brain were determined by lipid peroxidation assay. T2 VO mice exhibited learning and memory impairment in the MWM and PA tests. Treatment with CE ameliorated the learning and memory impairment of T2VO mice. Furthermore, CE significantly reduced MDA level in the brain of T2VO mice. On the other hand, administration of CE did not attenuate learning and memory impairment induced by scopolamine in mice. The present study demonstrated ameliorating effect of CE on learning and memory impairment in T2VO mice. Furthermore, it is likely that the positive effect of CE observed could be, at least partly, accounted by its antioxidative property. Thus, CE might be beneficial for memory impairment in which oxidative stress is an underlying cause.

  13. Melatonin supplementation plus exercise behavior ameliorate insulin resistance, hypertension and fatigue in a rat model of type 2 diabetes mellitus.

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    Rahman, Md Mahbubur; Kwon, Han-Sol; Kim, Myung-Jin; Go, Hyeon-Kyu; Oak, Min-Ho; Kim, Do-Hyung

    2017-08-01

    The objective was to investigate the effects of melatonin and exercise on insulin resistance (IR), hypertension and fatigue syndrome in a rat model of type 2 diabetes mellitus (T2DM). Rats were divided into 5 groups namely normal control (NC), T2DM control group (DC), diabetes plus exercise (DE), diabetes plus oral melatonin supplement (DM) and diabetes plus melatonin and exercise (DME) groups. Melatonin was administered orally 5mg/kg twice daily and 40min swimming/day 5days/week were regimented after diabetes induction. Blood pressure, fasting blood glucose, insulin, IR, serum leptin, lipid profiles, inflammatory cytokines, lipid peroxidation increased significantly (Pmelatonin ameliorated markedly hypertension, IR, biochemical alteration induced by diabetes and significantly increased exercise performance (PMelatonin supplementation in combination with exercise behavior may ameliorate IR, hypertension and exercise performance or fatigue possibly by improving antioxidative activities, hyperlipidemia, inflammatory cytokines via up-regulation of GLUT4, PGC-1 α and mitochondrial biogenesis in T2DM rats. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Ginsenoside Re Ameliorates Brain Insulin Resistance and Cognitive Dysfunction in High Fat Diet-Induced C57BL/6 Mice.

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    Kim, Jong Min; Park, Chang Hyeon; Park, Seon Kyeong; Seung, Tae Wan; Kang, Jin Yong; Ha, Jeong Su; Lee, Du Sang; Lee, Uk; Kim, Dae-Ok; Heo, Ho Jin

    2017-04-05

    The ameliorating effects of ginsenoside Re (G Re) on high fat diet (HFD)-induced insulin resistance in C57BL/6 mice were investigated to assess its physiological function. In the results of behavioral tests, G Re improved cognitive dysfunction in diabetic mice using Y-maze, passive avoidance, and Morris water maze tests. G Re also significantly recovered hyperglycemia and fasting blood glucose level. In the results of serum analysis, G Re decreased triglyceride (TG), total cholesterol (TCHO), low-density lipoprotein cholesterol (LDLC), glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) and increased the ratio of high-density lipoprotein cholesterol (HDLC). G Re regulated acetylcholine (ACh), acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), and oxidized glutathione (GSH)/total GSH by regulating the c-Jun N-terminal protein kinase (JNK) pathway. These findings suggest that G Re could be used to improve HFD-induced insulin resistance condition by ameliorating hyperglycemia via protecting the cholinergic and antioxidant systems in the mouse brains.

  15. Ameliorative Effect of Grape Seed Proanthocyanidin Extract on Cadmium-Induced Meiosis Inhibition During Oogenesis in Chicken Embryos.

    Science.gov (United States)

    Hou, Fuyin; Xiao, Min; Li, Jian; Cook, Devin W; Zeng, Weidong; Zhang, Caiqiao; Mi, Yuling

    2016-04-01

    Cadmium (Cd) is an environmental endocrine disruptor that has toxic effects on the female reproductive system. Here the ameliorative effect of grape seed proanthocyanidin extract (GSPE) on Cd-induced meiosis inhibition during oogenesis was explored. As compared with controls, chicken embryos exposed to Cd (3 µg/egg) displayed a changed oocyte morphology, decreased number of meiotic germ cells, and decreased expression of the meiotic marker protein γH2AX. Real time RT-PCR also revealed a significant down-regulation in the mRNA expressions of various meiosis-specific markers (Stra8, Spo11, Scp3, and Dmc1) together with those of Raldh2, a retinoic acid (RA) synthetase, and of the receptors (RARα and RARβ). In addition, exposure to Cd increased the production of H2 O2 and malondialdehyde in the ovaries and caused a corresponding reduction in glutathione and superoxide dismutase. Simultaneous supplementation of GSPE (150 µg/egg) markedly alleviated the aforementioned Cd-induced embryotoxic effects by upregulating meiosis-related proteins and gene expressions and restoring the antioxidative level. Collectively, the findings provided novel insights into the underlying mechanism of Cd-induced meiosis inhibition and indicated that GSPE might potentially ameliorate related reproductive disorders. © 2016 Wiley Periodicals, Inc.

  16. The ameliorative effect of thymol against hydrocortisone-induced hepatic oxidative stress injury in adult male rats.

    Science.gov (United States)

    Aboelwafa, Hanaa R; Yousef, Hany N

    2015-08-01

    The aim of the present study was to investigate whether hydrocortisone induces oxidative stress in hepatocytes and to evaluate the possible ameliorative effect of thymol against such hepatic injury. Twenty-four adult male rats were divided into control, thymol, hydrocortisone, and hydrocortisone+thymol groups. The 4 groups were treated daily for 15 days. Hydrocortisone significantly induced oxidative stress in the liver tissues, marked by increased serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total oxidative capacity (TOC), and tumor necrosis factor-alpha (TNF-α) accompanied by marked decline of serum levels of total protein, albumin, and total antioxidant capacity (TAC). Also, marked elevation in the levels of the thiobarbituric acid reactive substances (TBARS) and TNF-α, beside significant decrease in the level of glutathione (GSH) in hepatic tissues were recorded. These biochemical alterations were accompanied by histopathological changes marked by destruction of the normal hepatic architecture, in addition to ultrastructural alterations represented by degenerative features covering almost all the cytoplasmic organelles of the hepatocytes. Supplementation of hydrocortisone-treated rats with thymol reversed most of the biochemical, histological, and ultrastructural alterations. The results of our study confirm that thymol has strong ameliorative effect against hydrocortisone-induced oxidative stress injury in hepatic tissues.

  17. Convolvulus pluricaulis (Shankhapushpi) ameliorates human microtubule-associated protein tau (hMAPτ) induced neurotoxicity in Alzheimer's disease Drosophila model.

    Science.gov (United States)

    Kizhakke P, Anupama; Olakkaran, Shilpa; Antony, Anet; Tilagul K, Siddanna; Hunasanahally P, Gurushankara

    2017-10-16

    Convolvulus pluricaulis (Shankhapushpi) has long been used as traditional herbal medicine in India as nerve tonic. We studied the neuroprotective effects of C. pluricaulis extract (aqueous) against human microtubule-associated protein tau (hMAPτ) induced neurotoxicity in Alzheimer's disease (AD) Drosophila model. We analysed the lifespan, locomotor activity, τ protein level, reactive oxygen species (ROS), lipid peroxidation (LPO), catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities in 10 th , 20 th and 30 th days old control (wild type), τ control tauopathy Drosophila reared on C. pluricaulis supplemented with regular food or regular standard food. C. pluricaulis significantly offsets hMAPτ induced early death and extends the lifespan and diminishes the level of τ protein in tauopathy Drosophila. C. pluricaulis also enhances the antioxidant enzyme activities and ameliorates the τ-induced oxidative stress and restore the depleted AChE activity in the fly model. This study provides the first evidence that supplementation of C. pluricaulis along with the regular standard food ameliorate the neurotoxic effect of hMAPτ in AD Drosophila model and also reveals that it is a potent neuroprotective agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Purified Betacyanins from Hylocereus undatus Peel Ameliorate Obesity and Insulin Resistance in High-Fat-Diet-Fed Mice.

    Science.gov (United States)

    Song, Haizhao; Chu, Qiang; Xu, Dongdong; Xu, Yang; Zheng, Xiaodong

    2016-01-13

    Natural bioactive compounds in food have been shown to be beneficial in preventing the development of obesity, diabetes, and other metabolic diseases. Increasing evidence indicates that betacyanins possess free-radical-scavenging and antioxidant activities, suggesting their beneficial effects on metabolic disorders. The main objective of this study was to isolate and identify the betaycanins from Hylocereus undatus (white-fleshed pitaya) peel and evaluate their ability to ameliorate obesity, insulin resistance, and hepatic steatosis in high-fat-diet (HFD)-induced obese mice. The purified pitaya peel betacyanins (PPBNs) were identified by liquid chromatography/tandem mass spectrometry (LC/MS/MS), and the male C57BL/6 mice were fed a low-fat diet, HFD, or HFD supplemented with PPBNs for 14 weeks. Our results showed that the white-fleshed pitaya peel contains 14 kinds of betacyanins and dietary PPBNs reduced HFD-induced body weight gain and ameliorated adipose tissue hypertrophy, hepatosteatosis, glucose intolerance, and insulin resistance. Moreover, the hepatic gene expression analysis indicated that PPBN supplementation increased the expression levels of lipid-metabolism-related genes (AdipoR2, Cpt1a, Cpt1b, Acox1, PPARγ, Insig1, and Insig2) and FGF21-related genes (β-Klotho and FGFR1/2) but decreased the expression level of Fads2, Fas, and FGF21, suggesting that the protective effect of PPBNs might be associated with the induced fatty acid oxidation, decreased fatty acid biosynthesis, and alleviated FGF21 resistance.

  19. Reactive oxygen species are involved in regulating α1-adrenoceptor-activated vascular smooth muscle contraction

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    Tsai Ming-Ho

    2010-08-01

    Full Text Available Abstract Background Reactive oxygen species (ROS were shown to mediate aberrant contractility in hypertension, yet the physiological roles of ROS in vascular smooth muscle contraction have remained elusive. This study aimed to examine whether ROS regulate α1-adrenoceptor-activated contraction by altering myosin phosphatase activities. Methods Using endothelium-denuded rat tail artery (RTA strips, effects of anti-oxidants on isometric force, ROS production, phosphorylation of the 20-kDa myosin light chain (MLC20, and myosin phosphatase stimulated by α1-adrenoceptor agonist phenylephrine were examined. Results An antioxidant, N-acetyl-L-cysteine (NAC, and two NADPH oxidase inhibitors, apocynin and VAS2870, dose-dependently inhibited contraction activated by phenylephrine. Phenylephrine stimulated superoxide anion production that was diminished by the pretreatment of apocynin, VAS2870, superoxide scavenger tiron or mitochondria inhibitor rotenone, but not by xanthine oxidase inhibitor allopurinol or cyclooxygenase inhibitor indomethacin. Concurrently, NADPH oxidase activity in RTA homogenates increased within 1 min upon phenylephrine stimulation, sustained for 10 min, and was abolished by the co-treatment with apocynin, but not allopurinol or rotenone. Phenylephrine-induced MLC20 phosphorylation was dose-dependently decreased by apocynin. Furthermore, apocynin inhibited phenylephrine-stimulated RhoA translocation to plasma membrane and phosphorylation of both myosin phosphatase regulatory subunit MYPT1Thr855 and myosin phosphatase inhibitor CPI-17Thr38. Conclusions ROS, probably derived from NADPH oxidase and mitochondria, partially regulate α1-adrenoceptor-activated smooth muscle contraction by altering myosin phosphatase-mediated MLC20 phosphorylation through both RhoA/Rho kinase- and CPI-17-dependent pathways.

  20. Calcium Release Mediated by Redox-Sensitive RyR2 Channels Has a Central Role in Hippocampal Structural Plasticity and Spatial Memory.

    Science.gov (United States)

    More, Jamileth Y; Bruna, Barbara A; Lobos, Pedro E; Galaz, José L; Figueroa, Paula L; Namias, Silvia; Sánchez, Gina L; Barrientos, Genaro C; Valdés, José L; Paula-Lima, Andrea C; Hidalgo, Cecilia; Adasme, Tatiana

    2018-03-01

    Previous studies indicate that hippocampal synaptic plasticity and spatial memory processes entail calcium release from intracellular stores mediated by ryanodine receptor (RyR) channels. In particular, RyR-mediated Ca 2+ release is central for the dendritic spine remodeling induced by brain-derived neurotrophic factor (BDNF), a neurotrophin that stimulates complex signaling pathways leading to memory-associated protein synthesis and structural plasticity. To examine if upregulation of ryanodine receptor type-2 (RyR2) channels and the spine remodeling induced by BDNF entail reactive oxygen species (ROS) generation, and to test if RyR2 downregulation affects BDNF-induced spine remodeling and spatial memory. Downregulation of RyR2 expression (short hairpin RNA [shRNA]) in primary hippocampal neurons, or inhibition of nitric oxide synthase (NOS) or NADPH oxidase, prevented agonist-mediated RyR-mediated Ca 2+ release, whereas BDNF promoted cytoplasmic ROS generation. RyR2 downregulation or inhibitors of N-methyl-d-aspartate (NMDA) receptors, or NOS or of NADPH oxidase type-2 (NOX2) prevented RyR2 upregulation and the spine remodeling induced by BDNF, as did incubation with the antioxidant agent N-acetyl l-cysteine. In addition, intrahippocampal injection of RyR2-directed antisense oligodeoxynucleotides, which caused significant RyR2 downregulation, caused conspicuous defects in a memorized spatial memory task. The present novel results emphasize the key role of redox-sensitive Ca 2+ release mediated by RyR2 channels for hippocampal structural plasticity and spatial memory. Based on these combined results, we propose (i) that BDNF-induced RyR2-mediated Ca 2+ release and ROS generation via NOS/NOX2 are strictly required for the dendritic spine remodeling and the RyR2 upregulation induced by BDNF, and (ii) that RyR2 channel expression is crucial for spatial memory processes. Antioxid. Redox Signal. 00, 000-000.

  1. Antagonistic effect of Pseudomonas graminis CPA-7 against foodborne pathogens in fresh-cut apples under simulated commercial conditions.

    Science.gov (United States)

    Alegre, Isabel; Viñas, Inmaculada; Usall, Josep; Anguera, Marina; Altisent, Rosa; Abadias, Maribel

    2013-04-01

    Recently, we reported that the application of the strain CPA-7 of Pseudomonas graminis, previously isolated from apple, could reduce the population of foodborne pathogens on minimally processed (MP) apples and peaches under laboratory conditions. Therefore, the objective of the present work was to find an antioxidant treatment and a packaging atmosphere condition to improve CPA-7 efficacy in reducing a cocktail of four Salmonella and five Listeria monocytogenes strains on MP apples under simulated commercial processing. The effect of CPA-7 application on apple quality and its survival to simulated gastric stress were also evaluated. Ascorbic acid (2%, w/v) and N-acetyl-l-cysteine (1%, w/v) as antioxidant treatments reduced Salmonella, L. monocytogenes and CPA-7 recovery, meanwhile no reduction was observed with NatureSeal(®) AS1 (NS, 6%, w/v). The antagonistic strain was effective on NS-treated apple wedges stored at 10 °C with or without modified atmosphere packaging (MAP). Then, in a semi-commercial assay, efficacy of CPA-7 inoculated at 10(5) and 10(7) cfu mL(-1) against Salmonella and L. monocytogenes strains on MP apples with NS and MAP and stored at 5 and 10 °C was evaluated. Although high CPA-7 concentrations/populations avoided Salmonella growth at 10 °C and lowered L. monocytogenes population increases were observed at both temperatures, the effect was not instantaneous. No effect on apple quality was detected and CPA-7 did not survived to simulated gastric stress throughout storage. Therefore, CPA-7 could avoid pathogens growth on MP apples during storage when use as part of a hurdle technology in combination with disinfection techniques, low storage temperature and MAP. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Antioxidant Properties of Probiotic Bacteria.

    Science.gov (United States)

    Wang, Yang; Wu, Yanping; Wang, Yuanyuan; Xu, Han; Mei, Xiaoqiang; Yu, Dongyou; Wang, Yibing; Li, Weifen

    2017-05-19

    Oxidative stress defines a condition in which the prooxidant-antioxidant balance in the cell is disturbed, resulting in DNA hydroxylation, protein denaturation, lipid peroxidation, and apoptosis, ultimately compromising cells' viability. Probiotics have been known for many beneficial health effects, and the consumption of probiotics alone or in food shows that strain-specific probiotics can present antioxidant activity and reduce damages caused by oxidation. However, the oxidation-resistant ability of probiotics, especially the underling mechanisms, is not properly understood. In this view, there is interest to figure out the antioxidant property of probiotics and summarize the mode of action of probiotic bacteria in antioxidation. Therefore, in the present paper, the antioxidant mechanisms of probiotics have been reviewed in terms of their ability to improve the antioxidant system and their ability to decrease radical generation. Since in recent years, oxidative stress has been associated with an altered gut microbiota, the effects of probiotics on intestinal flora composition are also elaborated.

  3. Selenium antagonizes cadmium-induced apoptosis in chicken spleen but not involving Nrf2-regulated antioxidant response.

    Science.gov (United States)

    Chen, Menghao; Li, Xiaojing; Fan, Ruifeng; Cao, Changyu; Yao, Haidong; Xu, Shiwen

    2017-11-01

    The nuclear transcription factor NF-E2-related factor 2 (Nrf2) binds to antioxidant response elements (AREs) and is involved in the regulation of genes participated in defending cells against oxidative damage, which have been confirmed in animal models. Selenium (Se), known as an important element in the regulation of antioxidant activity, can antagonize Cadmium (Cd) toxicity in birds. However, the role of Nrf2 in selenium-cadmium interaction has not been reported in birds. To further explore the mechanism of selenium attenuating spleen toxicity induced by cadmium in chickens, cadmium chloride (CdCl 2 , 150mg/kg) and sodium selenite (Na 2 SeO 3 , 2mg/kg) were co-administrated or individually administered in the diet of chickens for 90 days. The results showed that Cd exposure increased the level of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) and decreased the antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione peroxidase (Gpx), total antioxidative capacity (T-AOC), catalase (CAT). Cd exposure increased obviously nuclear accumulation of Nrf2, and the expression of Nrf2 downstream heme oxygenase-1 (HO-1) and NAD(P)H: quinine oxidoreductase 1 (NQO1), reduced the expression of Kelch-like ECH-associated protein (keap1), Gpx-1 and thioredoxin reductase-1 (TrxR1). In addition, Cd induced the increase of bak, caspase9, p53, Cyt c mRNA levels, increased bax/bcl-2 ratio, increased caspase3 mRNA and protein levels. Selenium treatment reduced the accumulation of Cd in the spleen, attenuates Cd-induced Nrf2 nuclear accumulation, enhanced antioxidant enzyme activities, ameliorated Cd-induced oxidative stress and apoptosis in the spleen. In summary, our results demonstrate that Se ameliorated spleen toxicity induced by cadmium by modulating the antioxidant system, independently of Nrf2-regulated antioxidant response pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. The Protective Effect of Antioxidants on Oxidative Stress in Rats Exposed to the 950 MHz Electromagnetic Field

    International Nuclear Information System (INIS)

    Ibrahim, N.K.; Gharib, O.A.

    2010-01-01

    Studies have linked cell phone radiation to health problems such as headaches, high blood pressure, cancer and more. There is a latency period for most diseases and it may take years and more studies before the required weight of evidence is established. But the effects are cumulative and precautions should be taken now before it is too late. The aim of the present study was to investigate if supplementation with antioxidants would protect heart and liver tissues from harmful radiation emitted by cell phone. Thirty two male albino rats were randomly divided into four equal groups: I- Control, II- Antioxidants treated group, III- 950 MHz EMR, IV- 950 MHz EMR + antioxidants. A 950 MHz EMR radiation (217-Hz pulse rate, 2-W maximum peak power, SAR Specific Absorption Rate 1 .6 W/Kg) was applied to groups III and IV 60 min/day, for 30 days using an experimental exposure device. Antioxidants supplement (Vitamins A, E and C + Se) was administered to rats daily, by gavages, during the period of exposure to EMR. Malondialdehyde (MDA) and nitric oxide (NO) were used as markers of oxidative damage. Catalase (CAT), and glutathione peroxidase (GSHPx) activities were studied to evaluate the changes of antioxidant status. Biochemical analysis performed at the end of EMR exposure showed that supplementation with antioxidants has significantly attenuated EMR-induced oxidative stress signified by a decrease in the amount of MDA and an increase the activity of CAT and GSHPx in heart and liver tissues. Amelioration of oxidative damage was substantiated by significant amelioration in the activity of serum enzymes creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate amino-transferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). According to the results obtained in the present study, it could be concluded that antioxidants supplementation may protect from mobile phone-induced oxidative damage in heart and liver tissues

  5. The ameliorative effects of Moringa oleifera leaf extract on ...

    African Journals Online (AJOL)

    ADEYEYE

    2017-03-13

    Mar 13, 2017 ... *Correspondence: Tel.: +2348033858362; E-mail: misibisol@yahoo.com. Abstract. The present study was aimed at evaluating the ameliorating effects of Moringa oleifera extract compared to ... At the end of the exposure, 0.2ml of blood samples obtained from individual rat in each group were suspended in ...

  6. Antibiotics can ameliorate circulatory complications of liver cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn Stæhr; Schaffalitzky de Muckadell, Ove B

    2011-01-01

    . This review focuses on how broad spectrum antibiotics can ameliorate the haemodynamic consequences of bacterial translocation. It is possible that the use of broad spectrum antibiotics in the future may be used to prevent other complications of liver cirrhosis than spontaneous bacterial peritonitis...

  7. Designing urban parks that ameliorate the effects of climate change

    NARCIS (Netherlands)

    Brown, R.D.; Vanos, J.; Kenny, N.; Lenzholzer, S.

    2015-01-01

    Many inhabitants of cities throughout the world suffer from health problems and discomfort that are caused by overheating of urban areas, and there is compelling evidence that these problems will be exacerbated by global climate change. Most cities are not designed to ameliorate these effects

  8. Bacterial mediated amelioration of drought stress in drought tolerant ...

    African Journals Online (AJOL)

    Bacterial mediated amelioration of drought stress in drought tolerant and susceptible cultivars of rice (Oryza sativa L.) YS Gusain, US Singh, AK Sharma. Abstract. In the present study, plant growth promoting rhizobacterial (PGPR) strains Pseudomonas fluorescence strain P2, Pseudomonas jessenii R62, Pseudomonas ...

  9. Cancer ameliorating potential of Phyllanthus amarus: In vivo and in ...

    African Journals Online (AJOL)

    Md. Sultan Ahmad

    2015-06-10

    Jun 10, 2015 ... ORIGINAL ARTICLE. Cancer ameliorating potential of Phyllanthus amarus: In vivo and in vitro studies against. Aflatoxin B1 toxicity. Md. Sultan Ahmad *, Sultana Bano, Shafaat Anwar. Department of Zoology, Shibli National (P.G) College, Azamgarh, U.P. 276001, India. Received 17 April 2015; accepted 14 ...

  10. Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol ...

    African Journals Online (AJOL)

    Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol-Induced Hepatotoxicity In Rats. ... Nigerian Quarterly Journal of Hospital Medicine ... the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure.

  11. Salvianolic Acid B Ameliorates Motor Dysfuntion in Spinal Cord ...

    African Journals Online (AJOL)

    Salvianolic Acid B Ameliorates Motor Dysfuntion in Spinal. Cord Injury Rats. Chong Xun, Shouyu Wang, Guang Chen, Yang Hu, Jiaqi Xie and Decheng Lv*. Department of ... Purpose: To evaluate the effect of salvianolic acid B (Sal B) treatment on the motor function of spinal ... China. All the animals were housed at 25 °C in.

  12. Dose-Dependent Amelioration of Gentamicin-Induced ...

    African Journals Online (AJOL)

    increase in serum urea and creatine while 3ml/kg of the same drug completely prevented the increase in serum urea and creatine in this model. Conclusion: Vitamin B-complex dose-dependently ameliorated gentamicin-induced nephrotoxicity in adult Swiss albino rats when given intramuscularly. This finding may have ...

  13. The Effect of Vitamin E on Ameliorating Primary Dysmenorrhea: A ...

    African Journals Online (AJOL)

    Dysmenorrhea or painful menstruation is one of the most common problems of women. Using systematic review and meta‑analysis, this study aimed to determine the effect of vitamin E on ameliorating the intensity of pain of primary dysmenorrhea. Available databases comprising PubMed, Google Scholar, ISI, Science ...

  14. Ameliorative effects of Cnidoscolus aconitifolius on anaemia and ...

    African Journals Online (AJOL)

    This study was designed to evaluate the ameliorative effect of dietary supplementation of Cnidoscolus aconitifolius leaf on anaemia and changes in erythrocyte osmotic fragility in protein energy malnourished rats. Protein energy malnutrition has been associated with anaemia and changes in osmotic fragility, deformability ...

  15. Ameliorative effects of salt resistance on physiological parameters in ...

    African Journals Online (AJOL)

    Ameliorative effects of salt resistance on physiological parameters in the halophyte Salicornia bigelovii torr. with plant growth-promoting rhizobacteria. Edgar Omar Rueda-Puente, R Prabhaharan, B Murillo-Amador, F Ruiz-Espinoza, M Puente, RD Valdez-Cepeda ...

  16. Ameliorative effect of the hydroethanolic whole plant extract of ...

    African Journals Online (AJOL)

    At the end of the study, biochemical markers of nitrosative and oxidative stress status were determined. Results: DH (12.5, 50 and 100 mg/kg) significantly ameliorated haloperidol-induced catalepsy (bar test), spontaneous motor and working memory deficits (open field and elevated plus maze tests, respectively), ...

  17. Erratum: Unripe Musa paradisiaca Fruit Diet Ameliorates Impaired ...

    African Journals Online (AJOL)

    In the article “Unripe Musa paradisiaca Fruit Diet Ameliorates Impaired Glucose Regulation Caused by Iron-Induced Oxidative Stress” by Ige A.O, Oyekunle A.O, Olaoye M. O and Adewoye E.O which appeared on pages 301-308 of the September 2017 issue, it has been observed that the name of the second author was ...

  18. Using innovation platforms to scale out soil acidity- ameliorating ...

    African Journals Online (AJOL)

    Dr V.Kabambe

    2012-01-10

    Jan 10, 2012 ... ameliorating technologies in Dedza district in central. Malawi. V. H. Kabambe1* ... end of the project support in 2008, the participating farmers were willing to invest in the technology and raised funds for purchase ..... Engineering Commodity Group Project Meeting held at Mzuzu Hotel,. 10-15 August 1996.

  19. Ameliorative effects of Cnidoscolus aconitifolius on anaemia and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-06-03

    Jun 3, 2008 ... Accepted 28 April, 2008. This study was designed to evaluate the ameliorative effect of dietary supplementation of Cnidoscolus aconitifolius leaf on anaemia and changes in erythrocyte osmotic fragility in protein energy malnourished rats. Protein energy malnutrition has been associated with anaemia and ...

  20. The ameliorative effects of Moringa oleifera leaf extract on ...

    African Journals Online (AJOL)

    The present study was aimed at evaluating the ameliorating effects of Moringa oleifera extract compared to captopril and candesartan cilexetil on cardiovascular functions and osmotic fragility of rats exposed to petrol vapour. Twenty five adult male Wistar rats (130g-200g) were randomly grouped to five with five rats in a ...

  1. Potassium Bromate-induced Changes in the Adult Mouse Cerebellum Are Ameliorated by Vanillin.

    Science.gov (United States)

    Ben Saad, Hajer; Driss, Dorra; Jaballi, Imen; Ghozzi, Hanen; Boudawara, Ons; Droguet, Michael; Magné, Christian; Nasri, Monsef; Zeghal, Khaled Mounir; Hakim, Ahmed; Ben Amara, Ibtissem

    2018-02-01

    The current study aimed to elucidate the effect of vanillin on behavioral changes, oxidative stress, and histopathological changes induced by potassium bromate (KBrO3), an environmental pollutant, in the cerebellum of adult mice. The animals were divided into four groups: group 1 served as a control, group 2 received KBrO3, group 3 received KBrO3 and vanillin, and group 4 received only vanillin. We then measured behavioral changes, oxidative stress, and molecular and histological changes in the cerebellum. We observed significant behavioral changes in KBrO3-exposed mice. When investigating redox homeostasis in the cerebellum, we found that mice treated with KBrO3 had increased lipid peroxidation and protein oxidation in the cerebellum. These effects were accompanied by decreased Na+-K+ and Mg2+ ATPase activity and antioxidant enzyme gene expression when compared to the control group. Additionally, there was a significant increase in cytokine gene expression in KBrO3-treated mice. Microscopy revealed that KBrO3 intoxication resulted in numerous degenerative changes in the cerebellum that were substantially ameliorated by vanillin supplementation. Co-administration of vanillin blocked the biochemical and molecular anomalies induced by KBrO3. Our results demonstrate that vanillin is a potential therapeutic agent for oxidative stress associated with neurodegenerative diseases. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  2. Ameliorative effect of the cinnamon oil from Cinnamomum zeylanicum upon early stage diabetic nephropathy.

    Science.gov (United States)

    Mishra, Awanish; Bhatti, Rajbir; Singh, Amarjit; Singh Ishar, Mohan Paul

    2010-03-01

    The current study was designed to evaluate the ameliorative effect of the cinnamon oil upon early stage diabetic nephropathy owing to its antioxidant and antidiabetic effect. Cinnamon oil was extracted by hydro-distillation of the dried inner bark of Cinnamomum zeylanicum Blume. Further characterization of the extracted oil was carried out using IR, (1)H-NMR, and (13)C-NMR techniques. Early stage of diabetic nephropathy was induced by administration of alloxan (150 mg/kg, I. P.). Cinnamon oil was administered at varying doses (5, 10, 20 mg/kg; I. P.) while the level of fasting blood glucose, total cholesterol, high density lipoprotein, urea, thiobarbituric acid reactive substances, reduced glutathione, and catalase were determined. These parameters in cinnamon oil treated groups were compared with those of standard (glipizide; 10 mg/kg) and vehicle treated groups in order to investigate if cinnamon oil confers a significant protection against diabetic nephropathy. Histological studies of the kidney proved the protective effect of cinnamon oil by reducing the glomerular expansion, eradicating hyaline casts, and decreasing the tubular dilatations. Our results indicate that the volatile oil from cinnamon contains more than 98 % cinnamaldehyde and that it confers dose-dependent, significant protection against alloxan-induced renal damage, the maximum decrease in fasting blood glucose having been achieved at the dose of 20 mg/kg. (c) Georg Thieme Verlag KG Stuttgart . New York.

  3. Amelioration of radiation induced oxidative stress using water soluble chitosan produced by Aspergillus niger

    International Nuclear Information System (INIS)

    EL-Sonbaty, S.M.; Swailam, H.M.; Noaman, E.

    2012-01-01

    Chitosan is a natural polysaccharide synthesized by a great number of living organisms and considered as a source of potential bioactive material and has many biological applications which are greatly affected by its solubility in neutral ph. In this study low molecular weight water soluble chitosan was prepared by chemical degradation of chitosan produced by Aspergillus niger using H 2 O 2 . Chitosan chemical structure was detected before and after treatment using FTIR spectrum, and its molecular weight was determined by its viscosity using viscometer. Its antioxidant activity against gamma radiation was evaluated in vivo using rats. Rats were divided into 4 groups; group 1: control, group 2: exposed to acute dose of gamma radiation (6 Gy), group 3: received water soluble chitosan, group 4: received water soluble chitosan then exposed to gamma radiation as group 2. Gamma radiation significantly increased malonaldehyde, decreased glutathione concentration, activity of superoxide dismutase, catalase, and glutatione peroxidase, while significantly increase the activity of alanine transferase, aspartate transferase, urea and creatinine concentration. Administration of water soluble chitosan has ameliorated induced changes caused by gamma radiation. It could be concluded that water soluble chitosan by scavenging free radicals directly or indirectly may act as a potent radioprotector against ionizing irradiation.

  4. Ameliorative effect of astaxanthin on endothelial dysfunction in streptozotocin-induced diabetes in male rats.

    Science.gov (United States)

    Zhao, Zi-Wen; Cai, Wei; Lin, Yun-Ling; Lin, Qing-Fei; Jiang, Qiong; Lin, Zhang; Chen, Liang-Long

    2011-01-01

    The present study was designed to examine whether astaxanthin (ASX, 3,3-dihydroxybeta, beta-carotene-4,4-dione, CAS 472-61-7), a dietary antioxidant carotenoid that is naturally present in algae, crustaceans, and fish, has a protective effect on endothelial dysfunction of aortas in diabetic rats and the possible molecular mechanism involved. Male Wistar rats were randomly divided into four groups: control rats, diabetic rats, diabetic rats treated with ASX (10 mg/kg/d), and control rats treated with ASX. Type 1 diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/ kg). STZ-induced diabetes in rats was complicated with excessive oxidative stress and endothelial dysfunction, increased serum oxidized low-density lipoprotein (ox-LDL) and aortic malondialdehyde (MDA) levels, inhibited endothelium-dependent vasorelaxation to acetylcholine (ACh) and unaffected endothelium-dependent vasorelaxation to sodium nitroprusside (SNP). Simultaneously, lectin-like oxLDL receptor-i (LOX-1) expression was enhanced and endothelial nitric oxide (NO) synthase (eNOS) expression was reduced in the aortas of diabetic rats. ASX treatment could significantly decrease serum oxLDL and aortic MDA levels, attenuate blunted endothelium-dependent vasodilator responses to ACh, upregulate eNOS expression, and decrease LOX-1 expression. These results indicated that ASX could ameliorate diabetic endothelial dysfunction by inhibiting the ox-LDLLOX-1-eNOS pathway. Treatment with ASX might be clinically useful for diabetic complications associated with endothelial dysfunction.

  5. Role of berberine in ameliorating Schistosoma mansoni-induced hepatic injury in mice

    Directory of Open Access Journals (Sweden)

    Mohamed A Dkhi

    2014-01-01

    Full Text Available BACKGROUND: Schistosomiasis is caused by helminth parasites of the genus Schistosoma. Berberine chloride (BER, an isoquinoline alkaloid, has been used in vivo for its antiparasitic, antioxidant and hepatoprotective properties. In this study, the protective effect of BER and praziquantel has been compared for the extent of schistosomiasis-induced oxidative stress in hepatic tissue of mice. RESULTS: S. mansoni was able to induce inflammation and injury to the liver, evidenced (i by an increase in inflammatory cellular infiltrations, dilated sinusoids and vacuolated hepatocytes, (ii by decreased levels of alanine and aspartate aminotransferases and increased levels of alkaline phosphatase, γ-glutamyl transferase in the liver homogenate, (iii by increased production of nitric oxide and thiobarbituric acid reactive substances, and (iv by lowered glutathione levels and decreased activities of catalase and superoxide dismutase, respectively. All these infection-induced parameters were significantly altered during BER treatment. In particular, berberine counteracted the S. mansoni-induced loss of glutathione and the activities of catalase and superoxide dismutase. CONCLUSION: Based on these results, it is concluded that berberine could ameliorate pre-existing liver damage and oxidative stress conditions due to schistosomiasis.

  6. Diesel Exhaust Particles Induce Impairment of Vascular and Cardiac Homeostasis in Mice: Ameliorative Effect of Emodin

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2015-07-01

    Full Text Available Background/Aim: There is strong epidemiological and clinical evidence that components of the cardiovascular system are adversely affected by particulate air pollutants through the generation of inflammation and oxidative stress. Emodin (1,3,8-trihydroxy-6-methylanthraquinone, which is commonly found in the roots of rhubarb plant, has strong antioxidant and anti-inflammatory effects. However, its possible protective effect on the cardiovascular effect of particulate air pollutants has never been reported before. Methods: We tested, in Tuck-Ordinary mice, the possible ameliorative effect of emodin on the acute (24h cardiovascular effects of diesel exhaust particles (DEP, 1 mg/kg or saline (control. Emodin (4 mg/kg was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty four h following DEP exposure, several cardiovascular endpoints were assessed. Results: Emodin significantly prevented the increase of leukocyte (n=8, Pin vivo prothrombotic effect of DEP in pial arterioles (n=6, Pin vitro in whole blood (n=4-5, PConclusion: We conclude that emodin treatment has consistently protected against DEP-induced impairment of vascular and cardiac homeostasis in mice. Our study provides experimental evidence that the use of functional food such as emodin, pending further studies, can be considered a useful agent and may have the potential to protect or mitigate the cardiovascular detrimental effects observed in people living in cities with high concentrations of particulate air pollution.

  7. Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence.

    Science.gov (United States)

    Sachdeva, Anand Kamal; Kuhad, Anurag; Tiwari, Vinod; Chopra, Kanwaljit

    2009-12-28

    Three decades after the coining of the term chronic fatigue syndrome, the diagnosis of this illness is still symptom based and the aetiology remains elusive. Chronic fatigue syndrome pathogenesis seems to be multifactorial and the possible involvement of immune system is supported. The present study was designed to evaluate the effects of the epigallocatechin gallate in a mouse model of immunologically induced chronic fatigue. On 19th day, after lipopolysaccharide/Brucella abortus administration, the mice showed significant increase in immobility period, post swim fatigue and thermal hyperalgesia. Behavioral deficits were coupled with enhanced oxidative-nitrosative stress as evident by increased lipid peroxidation, nitrite levels and decreased endogenous antioxidant enzymes (superoxide dismutase, reduced glutathione and catalase) and inflammation (increased levels of tumor necrosis factor-alpha and tissue growth factor-beta). Chronic treatment with epigallocatechin gallate restored these behavioral and biochemical alterations in mice. The present study points out towards the beneficial effect of epigallocatechin gallate in the amelioration of chronic fatigue syndrome and thus may provide a new, effective and powerful strategy to treat chronic fatigue syndrome.

  8. Ameliorative effect of ethyl pyruvate in neuropathic pain induced by chronic constriction injury of sciatic nerve

    Directory of Open Access Journals (Sweden)

    Varsha J. Bansode

    2014-01-01

    Full Text Available Objective: The present study was designed to investigate the ameliorative effects of ethyl pyruvate (EP in chronic constriction injury (CCI-induced painful neuropathy in rats. Materials and Methods: EP 50 and 100 mg/kg was administered for 21 consecutive days starting from the day of surgery. The effects of EP in the paw pressure, acetone drop, and tail heat immersion tests were assessed, reflecting the degree of mechanical hyperalgesia, cold allodynia, and spinal thermal sensation, respectively. Axonal degeneration of the sciatic nerve was assessed histopathologically. The levels of thiobarbituric acid reactive species, reduced glutathione (GSH, catalase (CAT, and superoxide dismutase (SOD were determined to assess oxidative stress. Key Findings: Administration of 50 and 100 mg/kg EP attenuated the reduction of nociceptive threshold in the paw pressure, acetone drop, and tail heat immersion tests. EP 100 mg/kg significantly attenuated reactive changes in histopathology and increase in oxidative stress. Conclusion: EP 100 mg/kg showed beneficial activity against nerve trauma-induced neuropathy. Hence, it can be used as a better treatment option in neuropathic pain (NP. The observed antinociceptive effects of EP may possibly be attributed to its antioxidant and anti-inflammatory activity.

  9. The Green Tea Catechin Epigallocatechin Gallate Ameliorates Graft-versus-Host Disease.

    Directory of Open Access Journals (Sweden)

    Sabine Westphal

    Full Text Available Allogeneic hematopoetic stem cell transplantation (allo-HSCT is a standard treatment for leukemia and other hematologic malignancies. The major complication of allo-HSCT is graft-versus-host-disease (GVHD, a progressive inflammatory illness characterized by donor immune cells attacking the organs of the recipient. Current GVHD prevention and treatment strategies use immune suppressive drugs and/or anti-T cell reagents these can lead to increased risk of infections and tumor relapse. Recent research demonstrated that epigallocatechin gallate (EGCG, a component found in green tea leaves at a level of 25-35% at dry weight, may be useful in the inhibition of GVHD due to its immune modulatory, anti-oxidative and anti-angiogenic capacities. In murine allo-HSCT recipients treated with EGCG, we found significantly reduced GVHD scores, reduced target organ GVHD and improved survival. EGCG treated allo-HSCT recipients had significantly higher numbers of regulatory T cells in GVHD target organs and in the blood. Furthermore, EGCG treatment resulted in diminished oxidative stress indicated by significant changes of glutathione blood levels as well as glutathione peroxidase in the colon. In summary, our study provides novel evidence demonstrating that EGCG ameliorates lethal GVHD and reduces GVHD-related target organ damage. Possible mechanisms are increased regulatory T cell numbers and reduced oxidative stress.

  10. Ameliorating effect of vitamin E on in vitro development of preimplantation buffalo embryos.

    Science.gov (United States)

    Thiyagarajan, B; Valivittan, K

    2009-04-01

    Oxidative stress has been implicated in the etiology of defective embryo development. Vitamin E is an effective lipid-soluble antioxidant, protecting cell membranes from peroxidative damage. In this context, this study was undertaken to find if supplementation of vitamin E in culture medium could ameliorate the developmental competence of preimplantation buffalo embryos. Vitamin E was supplemented in maturation/embryo culture medium at concentrations of 0, 50, 100, 200 and 400 microM. The developmental competence of buffalo embryos was assessed by observing the cleavage, morulae, blastocyst rate, total cell count and comet assay. Vitamin E had no significant effect in maturation medium. Vitamin E in embryo culture medium under 5% O(2) significantly reduced blastocyst formation in the 400 microM supplemented group. Culture under 20% O(2) enhanced the frequency of blastocyst formation, total cell count and significantly reduced comet tail in the 100 microM supplemented group (P Vitamin E in ECM for the first 72 h of culture period enhanced blastocyst rate and total cell number in the 100 microM group (P Vitamin E may enhance the developmental competence of buffalo embryos in vitro by protecting them from oxidative stress.

  11. Tempol, a Superoxide Dismutase-Mimetic Drug, Ameliorates Progression of Renal Disease in CKD Mice

    Directory of Open Access Journals (Sweden)

    Wei Ding

    2015-07-01

    Full Text Available Background: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD and antioxidants may ameliorate disease progression. We investigate the beneficial effect of Tempol, a superoxide dismutase-mimetic drug, on progression of disease in a mouse model of CKD. Methods: CKD was surgically induced in c57BL/6 mice by 5/6 nephrectomy. Mice were randomly divided into 3 groups: sham group, 5/6 nephrectomized group (Nx and Nx+Tempol (2 mmol/l in drinking water. Mice were sacrificed at the end of 12 weeks. Renal function, structure as well as expression of key molecules involved in the pathogenesis of inflammation, fibrosis and progression in mice were measured. Results: Reduced body weight and impaired renal function (elevation on serum creatinine, blood urea nitrogen, urine albumin, segmental sclerosis and tubulointerstitial damage was demonstrated in Nx mice but was significantly improved by Tempol administration. Nx animals exhibited significantly elevated proinflammatory and profibrotic factors, activation of NF-κB, increased expression of NADPH oxidase related subunits (p47phox, p67phox, gp91phox, and elevated activation of TGF-ß/Smad3, EGFR, MAPK signaling pathway. Tempol inhibited NF-κB mediated inflammation, TGF-ß/Smad3-induced renal fibrosis as well as EGFR and MAPK signaling pathway activation. Conclusions: Tempol administration attenuated renal injury in CKD mice through NF-κB, TGF-ß/Smad3, redox-senstive EGFR activation and c-Raf/MEK/ERK pathways.

  12. Tempol, a Superoxide Dismutase-Mimetic Drug, Ameliorates Progression of Renal Disease in CKD Mice.

    Science.gov (United States)

    Ding, Wei; Wang, Bin; Zhang, Minmin; Gu, Yong

    2015-01-01

    Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD) and antioxidants may ameliorate disease progression. We investigate the beneficial effect of Tempol, a superoxide dismutase-mimetic drug, on progression of disease in a mouse model of CKD. CKD was surgically induced in c57BL/6 mice by 5/6 nephrectomy. Mice were randomly divided into 3 groups: sham group, 5/6 nephrectomized group (Nx) and Nx+Tempol (2 mmol/l in drinking water). Mice were sacrificed at the end of 12 weeks. Renal function, structure as well as expression of key molecules involved in the pathogenesis of inflammation, fibrosis and progression in mice were measured. Reduced body weight and impaired renal function (elevation on serum creatinine, blood urea nitrogen, urine albumin, segmental sclerosis and tubulointerstitial damage) was demonstrated in Nx mice but was significantly improved by Tempol administration. Nx animals exhibited significantly elevated proinflammatory and profibrotic factors, activation of NF-κB, increased expression of NADPH oxidase related subunits (p47phox, p67phox, gp91phox), and elevated activation of TGF-β/Smad3, EGFR, MAPK signaling pathway. Tempol inhibited NF-κB mediated inflammation, TGF-β/Smad3-induced renal fibrosis as well as EGFR and MAPK signaling pathway activation. Tempol administration attenuated renal injury in CKD mice through NF-κB, TGF-β/Smad3, redox-senstive EGFR activation and c-Raf/MEK/ERK pathways. © 2015 S. Karger AG, Basel.

  13. The ameliorative effect of gallic acid on pancreas lesions induced by 2.45 GHz electromagnetic radiation (Wi-Fi in young rats

    Directory of Open Access Journals (Sweden)

    Senay Topsakal

    2017-07-01

    Full Text Available The aim of this study was to investigate the effects of electromagnetic radiation (EMR on the pancreas tissue of young rats and the ameliorative effect of Gallic acid (GA. Six-week-old, 48 male rats were equally divided into four groups: Sham group, EMR group (2.45 GHz, EMR (2.45 GHz+GA group (30 mg/kg/daily orally and GA group (30 mg/kg/daily. After 30 days, serum and pancreatic tissue samples were harvested for biochemical, histopathological and immunohistochemical analysis. Serum amylase, lipase, glucose, and tissue malondialdehyde, total oxidant status and oxidative stress index were increased, whereas total antioxidant status decreased in the EMR group. The histopathological examination of the pancreases indicated slight degenerative changes in some pancreatic endocrine and exocrine cells and slight inflammatory cell infiltrations in the EMR group. At the immunohistochemical examination, marked increase was observed in calcitonin gene related protein and Prostaglandin E2 expressions in pancreatic cells in this group. There were no changes in interleukin-6 expirations. GA ameliorated biochemical and pathological findings in the EMR+GA group. These findings clearly demonstrate that EMR can cause degenerative changes in both endocrine and exocrine pancreas cells in rats during the developmental period and GA has an ameliorative effect.

  14. Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

    Directory of Open Access Journals (Sweden)

    Zeba Farooqui

    Full Text Available Cisplatin (CP is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p. respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism. Keywords: Cisplatin, Nigella sativa oil, Carbohydrate metabolism, Antioxidant

  15. Relationships among alcoholic liver disease, antioxidants, and antioxidant enzymes.

    Science.gov (United States)

    Han, Kyu-Ho; Hashimoto, Naoto; Fukushima, Michihiro

    2016-01-07

    Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide. The metabolism of ethanol generates reactive oxygen species, which play a significant role in the deterioration of alcoholic liver disease (ALD). Antioxidant phytochemicals, such as polyphenols, regulate the expression of ALD-associated proteins and peptides, namely, catalase, superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase. These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1-NF-E2-related factor-2 pathway and antioxidant responsive elements. Furthermore, these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines. These phenomena are likely induced via the regulation of mitogen-activating protein kinase (MAPK) pathways by plant antioxidants, similar to preconditioning in ischemia-reperfusion models. Although the relationship between plant antioxidants and ALD has not been adequately investigated, plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.

  16. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Bidya Dhar [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Tatireddy, Srujana [National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037 (India); Koneru, Meghana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Borkar, Roshan M. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Kumar, Jerald Mahesh [CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007 (India); Kuncha, Madhusudana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Srinivas, R. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Shyam Sunder, R. [Faculty of Pharmacy, Osmania University, Hyderabad 500 007 (India); Sistla, Ramakrishna, E-mail: sistla@iict.res.in [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India)

    2014-05-15

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

  17. Ameliorative potentials of cocoyam (Colocasia esculenta L.) and unripe plantain (Musa paradisiaca L.) on the relative tissue weights of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Eleazu, C O; Iroaganachi, M; Eleazu, K C

    2013-01-01

    To investigate the ameliorating potentials of cocoyam (Colocasia esculenta L.) and unripe plantain (Musa paradisiaca L.) incorporated feeds on the renal and liver growths of diabetic rats, induced with 55 and 65 mg/kg body weight of Streptozotocin. The blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity (SPGR) in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The chemical composition and antioxidant screening of the test feeds were carried out using standard techniques. Administration of the test feeds for 21 days to the diabetic rats of groups 4 and 5, resulted in 58.75% and 38.13% decreases in hyperglycemia and amelioration of their elevated urinary protein, glucose, SPGR, and relative kidney weights. The diabetic rats administered cocoyam incorporated feeds, had 2.71% and 19.52% increases in weight and growth rates, the diabetic rats administered unripe plantain incorporated feeds had 5.12% and 29.52% decreases in weight and growth rates while the diabetic control rats had 28.69%, 29.46%, 248.9% and 250.14% decreases in weights and growth rates. The cocoyam incorporated feeds contained higher antioxidants, minerals and phytochemicals except alkaloids than unripe plantain feed. Cocoyam and unripe plantain could be useful in the management of diabetic nephropathy.

  18. Ameliorative Potentials of Cocoyam (Colocasia esculenta L. and Unripe Plantain (Musa paradisiaca L. on the Relative Tissue Weights of Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    C. O. Eleazu

    2013-01-01

    Full Text Available Aim. To investigate the ameliorating potentials of cocoyam (Colocasia esculenta L. and unripe plantain (Musa paradisiaca L. incorporated feeds on the renal and liver growths of diabetic rats, induced with 55 and 65 mg/kg body weight of Streptozotocin. Method. The blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity (SPGR in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The chemical composition and antioxidant screening of the test feeds were carried out using standard techniques. Results. Administration of the test feeds for 21 days to the diabetic rats of groups 4 and 5, resulted in 58.75% and 38.13% decreases in hyperglycemia and amelioration of their elevated urinary protein, glucose, SPGR, and relative kidney weights. The diabetic rats administered cocoyam incorporated feeds, had 2.71% and 19.52% increases in weight and growth rates, the diabetic rats administered unripe plantain incorporated feeds had 5.12% and 29.52% decreases in weight and growth rates while the diabetic control rats had 28.69%, 29.46%, 248.9% and 250.14% decreases in weights and growth rates. The cocoyam incorporated feeds contained higher antioxidants, minerals and phytochemicals except alkaloids than unripe plantain feed. Conclusion. Cocoyam and unripe plantain could be useful in the management of diabetic nephropathy.

  19. In vitro dose and duration dependent approaches for the assessment of ameliorative effects of nanoconjugated vancomycin against Staphylococcus aureus infection induced oxidative stress in murine peritoneal macrophages.

    Science.gov (United States)

    Chakraborty, Subhankari Prasad; Pramanik, Panchanan; Roy, Somenath

    2016-02-01

    The present study was aimed to evaluate the in vitro ameliorative effect of nanoconjugated vancomycin (NV) against vancomycin sensitive and resistant strains of Staphylococcus aureus infection-induced oxidative stress in murine peritoneal macrophage. Peritoneal macrophages from mice were treated with VSSA and VRSA (5 × 10(6) CFU/mL), VSSA + NV (5-250 μg/ml) and VRSA + NV (5-250 μg/ml) for 18 h, having 3 h interval in culture media; and the superoxide anion generation, lipid peroxidation, protein oxidation, antioxidant enzymes status and glutathione enzymes activity were monitored. The significantly increased free radical generation, lipid peroxidation, protein carbonyls and oxidized glutathione levels were observed in VSSA and VRSA treated group as compared to control group; where as reduced glutathione level, antioxidant enzymes status and glutathione dependent enzymes were decreased significantly. All these changes come near to control in NV treated group in a dose and duration dependent fashion. Among the different doses and duration intervals of NV, maximum ameliorative effect was observed by 100 μg/ml for 12 h treatment which does not produce any damage to the cell. These findings suggest the potential use and beneficial role of nanoconjugated vancomycin as a modulator of S. aureus infection-induced cellular damage in murine peritoneal macrophage. Copyright © 2015. Published by Elsevier Ltd.

  20. Antioxidant defenses of mycorrhizal fungus infection against SO(2)-induced oxidative stress in Avena nuda seedlings.

    Science.gov (United States)

    Huang, L L; Yang, C; Zhao, Y; Xu, X; Xu, Q; Li, G Z; Cao, J; Herbert, S J; Hao, L

    2008-11-01

    Colonization of arbuscular mycorrhizal fungi Glomus mosseae increased Avena nuda seedling tolerance to SO(2) exposure, as indicated by elevated total plant biomass and ameliorative photosynthetic rate, when compared to the non-mycorrhizal plants. This is associated with an improved antioxidant capacity as shown by enhanced superoxide dismutase and catalase activity, increased ascorbic acid and glutathione content, and reduced malondialdehyde and hydrogen peroxide level in the mycorrhizal plants relative to the non-mycorrhizal plants under SO(2) exposure. The mycorrhizal fungi colonization had no effect on the stomatal conductance. To our knowledge, this is the first finding of this sort.

  1. Antioxidant supplements for liver diseases

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Gluud, Lise Lotte; Nikolova, Dimitrinka

    2011-01-01

    Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal.......Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal....

  2. Lutein protects dopaminergic neurons against MPTP-induced apoptotic death and motor dysfunction by ameliorating mitochondrial disruption and oxidative stress.

    Science.gov (United States)

    Nataraj, Jagatheesan; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin; Essa, Musthafa Mohammed

    2016-07-01

    Mitochondrial dysfunction and oxidative stress-mediated apoptosis plays an important role in various neurodegenerative diseases including Huntington's disease, Parkinson's disease (PD) and Alzheimer's disease (AD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the most widely used neurotoxin mimics the symptoms of PD by inhibiting mitochondrial complex I that stimulates excessive intracellular reactive oxygen species (ROS) and finally leads to mitochondrial-dependent apoptosis. Lutein, a carotenoid of xanthophyll family, is found abundantly in leafy green vegetables such as spinach, kale and in egg yolk, animal fat and human eye retinal macula. Increasing evidence indicates that lutein has offers benefits against neuronal damages during diabetic retinopathy, ischemia and AD by virtue of its mitochondrial protective, antioxidant and anti-apoptotic properties. Male C57BL/6 mice (23-26 g) were randomized and grouped in to Control, MPTP, and Lutein treated groups. Lutein significantly reversed the loss of nigral dopaminergic neurons by increasing the striatal dopamine level in mice. Moreover, lutein-ameliorated MPTP induced mitochondrial dysfunction, oxidative stress and motor abnormalities. In addition, lutein repressed the MPTP-induced neuronal damage/apoptosis by inhibiting the activation of pro-apoptotic markers (Bax, caspases-3, 8 and 9) and enhancing anti-apoptotic marker (Bcl-2) expressions. Our current results revealed that lutein possessed protection on dopaminergic neurons by enhancing antioxidant defense and diminishing mitochondrial dysfunction and apoptotic death, suggesting the potential benefits of lutein for PD treatment.

  3. Ameliorative properties of aqueous extract of Ficus thonningii on erythrocyte osmotic fragility induced by acetaminophen in Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    Victor Masekaven Ahur

    2013-12-01

    Full Text Available In vitro antioxidant and erythrocyte protecting activities by aqueous extract of Ficus thonningii leaves on blood cells were studied in acetaminophen treated rats. The extract was safe at limit dose of 5000 mg kg-1body weight. The extract demonstrated dose dependent antihemolytic effect at dose levels between 50 and 200 mg kg-1 body weight. The lowest antihemolytic effect was observed at dose level of 200 mg kg-1 body given the lowest percentage hemolysis of 10.53 ± 1.76%, whereas the highest percentage hemolysis at dose level of 50 mg kg-1 was 29.02 ± 7.45%. Hematology revealed erythrocytosis at dose levels of 100 and 200 mg kg-1 body weight. Hyper-globinemia and lymphocytopenia were observed at dose levels of 100 mg kg-1 and 200 mg kg-1, respectively. The extract effectively showed scavenging activity on a stable oxidative radical diphenylpicrylhydrazyl (DPPH and a significant ferric reducing antioxidant power (FRAP activity. The plausible erythrocyte membrane protective effect may be due to its free radical scavenging activity and hence the extract can be used to improve hematological parameters and ameliorate oxidative stress.

  4. Antioxidant relevance to human health.

    Science.gov (United States)

    Wahlqvist, Mark L

    2013-01-01

    Human ecology requires both oxygen and water with the generation from food of an immediate energy source, ATP, by oxidative phosphorylation. A continuing balance between oxidation and antioxidation is necessary for longer less-disabled lives, taking account of oxidative stresses and the critical roles of oxidants in defence against infection, tissue repair and signalling. Antioxidant capacity is derived both exogenously (from food, beverage and sunlight) and endogenously (from enzymatic and non-enzymatic pathways). A number of oxidant food factors service antioxidant metallo-enzymes. The capacity operates extra- or intracellularly. Uric acid is the major antioxidant in primate blood. Uric acid synthesis is increased by dietary fructose from fruit, sugary foods and drinks. This indirect antioxidant effect of fruit is separate from that attributable to its flavonoids. Alcohol also increases serum uric acid. Urate excess and retention is associated with disease. The high prevalence of hyperuricaemia in NE Asia presents a major public health dilemma in regard to putative benefits and risks. Foods with high antioxidant activity include berries, nuts and legumes, tomatoes and sweet potato leaves. Each of the antioxidants in these foods is pleiotropic being inter-alia anti-inflammatory, anti-angiogenic or anti-neoplastic. Moreover, food matrices and patterns contribute to the safety of antioxidant consumption. There is no evidence to date that isolated antioxidants as food supplements improve health outcomes or survival; and some that indicate unacceptable risk. Their use as biomarkers of food cannot justify their isolated use. Nevertheless, a spectrum of dietary pluripotential antioxidants for tissues, metabolic and immune systems is advantageous.

  5. Erythrocyte Antioxidant Protection of Rose Hips (Rosa spp.

    Directory of Open Access Journals (Sweden)

    C. Widén

    2012-01-01

    Full Text Available Rose hips are popular in health promoting products as the fruits contain high content of bioactive compounds. The aim of this study was to investigate whether health benefits are attributable to ascorbic acid, phenols, or other rose-hip-derived compounds. Freeze-dried powder of rose hips was preextracted with metaphosphoric acid and the sample was then sequentially eluted on a C18 column. The degree of amelioration of oxidative damage was determined in an erythrocyte in vitro bioassay by comparing the effects of a reducing agent on erythrocytes alone or on erythrocytes pretreated with berry extracts. The maximum protection against oxidative stress, 59.4±4.0% (mean ± standard deviation, was achieved when incubating the cells with the first eluted meta-phosphoric extract. Removal of ascorbic acid from this extract increased the protection against oxidative stress to 67.9±1.9%. The protection from the 20% and 100% methanol extracts was 20.8±8.2% and 5.0±3.2%, respectively. Antioxidant uptake was confirmed by measurement of catechin by HPLC-ESI-MS in the 20% methanol extract. The fact that all sequentially eluted extracts studied contributed to protective effects on the erythrocytes indicates that rose hips contain a promising level of clinically relevant antioxidant protection.

  6. Erythrocyte antioxidant protection of rose hips (Rosa spp.).

    Science.gov (United States)

    Widén, C; Ekholm, A; Coleman, M D; Renvert, S; Rumpunen, K

    2012-01-01

    Rose hips are popular in health promoting products as the fruits contain high content of bioactive compounds. The aim of this study was to investigate whether health benefits are attributable to ascorbic acid, phenols, or other rose-hip-derived compounds. Freeze-dried powder of rose hips was preextracted with metaphosphoric acid and the sample was then sequentially eluted on a C(18) column. The degree of amelioration of oxidative damage was determined in an erythrocyte in vitro bioassay by comparing the effects of a reducing agent on erythrocytes alone or on erythrocytes pretreated with berry extracts. The maximum protection against oxidative stress, 59.4 ± 4.0% (mean ± standard deviation), was achieved when incubating the cells with the first eluted meta-phosphoric extract. Removal of ascorbic acid from this extract increased the protection against oxidative stress to 67.9 ± 1.9%. The protection from the 20% and 100% methanol extracts was 20.8 ± 8.2% and 5.0 ± 3.2%, respectively. Antioxidant uptake was confirmed by measurement of catechin by HPLC-ESI-MS in the 20% methanol extract. The fact that all sequentially eluted extracts studied contributed to protective effects on the erythrocytes indicates that rose hips contain a promising level of clinically relevant antioxidant protection.

  7. Hepatoprotective and antioxidant activities of Tamarix nilotica flowers.

    Science.gov (United States)

    Abouzid, Sameh; Sleem, Amany

    2011-04-01

     Tamarix nilotica (Ehrenb.) Bunge (Tamaricaceae) is used in the Egyptian traditional medicine as an antiseptic agent. This plant has been known since pharaonic times and has been mentioned in medical papyri to expel fever, relieve headache, to draw out inflammation, and as an aphrodisiac. No scientific study is available about the biological effect of this plant.  This study aimed to evaluate the hydro-alcoholic extract (80%) of T. nilotica flowers for hepatoprotective and antioxidant activities.  Hepatoprotective activity was assessed using carbon tetrachloride-induced hepatic injury in rats by monitoring biochemical parameters. Antioxidant activity was evaluated in alloxan-induced diabetic rats. Biochemical markers of hepatic damage such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and tissue glutathione were determined in all groups.  Carbon tetrachloride (5 mL/kg body weight) enhanced the SGOT, SGPT, and ALP levels. There was a marked reduction in tissue glutathione level in diabetic rats. The hydro-alcoholic extract of T. nilotica (100 mg/kg body weight) ameliorated the adverse effects of carbon tetrachloride and returned the altered levels of biochemical markers near to the normal levels.

  8. Exposure to 9,10-phenanthrenequinone accelerates malignant progression of lung cancer cells through up-regulation of aldo-keto reductase 1B10.

    Science.gov (United States)

    Matsunaga, Toshiyuki; Morikawa, Yoshifumi; Haga, Mariko; Endo, Satoshi; Soda, Midori; Yamamura, Keiko; El-Kabbani, Ossama; Tajima, Kazuo; Ikari, Akira; Hara, Akira

    2014-07-15

    Inhalation of 9,10-phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust, exerts fatal damage against a variety of cells involved in respiratory function. Here, we show that treatment with high concentrations of 9,10-PQ evokes apoptosis of lung cancer A549 cells through production of reactive oxygen species (ROS). In contrast, 9,10-PQ at its concentrations of 2 and 5 μM elevated the potentials for proliferation, invasion, metastasis and tumorigenesis, all of which were almost completely inhibited by addition of an antioxidant N-acetyl-l-cysteine, inferring a crucial role of ROS in the overgrowth and malignant progression of lung cancer cells. Comparison of mRNA expression levels of six aldo-keto reductases (AKRs) in the 9,10-PQ-treated cells advocated up-regulation of AKR1B10 as a major cause contributing to the lung cancer malignancy. In support of this, the elevation of invasive, metastatic and tumorigenic activities in the 9,10-PQ-treated cells was significantly abolished by the addition of a selective AKR1B10 inhibitor oleanolic acid. Intriguingly, zymographic and real-time PCR analyses revealed remarkable increases in secretion and expression, respectively, of matrix metalloproteinase 2 during the 9,10-PQ treatment, and suggested that the AKR1B10 up-regulation and resultant activation of mitogen-activated protein kinase cascade are predominant mechanisms underlying the metalloproteinase induction. In addition, HPLC analysis and cytochrome c reduction assay in in vitro 9,10-PQ reduction by AKR1B10 demonstrated that the enzyme catalyzes redox-cycling of this quinone, by which ROS are produced. Collectively, these results suggest that AKR1B10 is a key regulator involved in overgrowth and malignant progression of the lung cancer cells through ROS production due to 9,10-PQ redox-cycling. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Particulate Matter Exposure Exacerbates High Glucose-Induced Cardiomyocyte Dysfunction through ROS Generation

    Science.gov (United States)

    Zuo, Li; Youtz, Dane J.; Wold, Loren E.

    2011-01-01

    Diabetes mellitus and fine particulate matter from diesel exhaust (DEP) are both important contributors to the development of cardiovascular disease (CVD). Diabetes mellitus is a progressive disease with a high mortality rate in patients suffering from CVD, resulting in diabetic cardiomyopathy. Elevated DEP levels in the air are attributed to the development of various CVDs, presumably since fine DEP (control cardiomyocyte function remain poorly understood. The purpose of the present study was to evaluate cardiomyocyte function and reactive oxygen species (ROS) generation in isolated rat ventricular myocytes exposed overnight to fine DEP (0.1 µg/ml), and/or high glucose (HG, 25.5 mM). Our hypothesis was that DEP exposure exacerbates contractile dysfunction via ROS generation in cardiomyocytes exposed to HG. Ventricular myocytes were isolated from male adult Sprague-Dawley rats cultured overnight and sarcomeric contractile properties were evaluated, including: peak shortening normalized to baseline (PS), time-to-90% shortening (TPS90), time-to-90% relengthening (TR90) and maximal velocities of shortening/relengthening (±dL/dt), using an IonOptix field-stimulator system. ROS generation was determined using hydroethidine/ethidium confocal microscopy. We found that DEP exposure significantly increased TR90, decreased PS and ±dL/dt, and enhanced intracellular ROS generation in myocytes exposed to HG. Further studies indicated that co-culture with antioxidants (0.25 mM Tiron and 0.5 mM N-Acetyl-L-cysteine) completely restored contractile function in DEP, HG and HG+DEP-treated myocytes. ROS generation was blocked in HG-treated cells with mitochondrial inhibition, while ROS generation was blocked in DEP-treated cells with NADPH oxidase inhibition. Our results suggest that DEP exacerbates myocardial dysfunction in isolated cardiomyocytes exposed to HG-containing media, which is potentially mediated by various ROS generation pathways. PMID:21850256

  10. Vitamin E synthetic derivate-TPGS-selectively induces apoptosis in jurkat t cells via oxidative stress signaling pathways: implications for acute lymphoblastic leukemia.

    Science.gov (United States)

    Ruiz-Moreno, Cristian; Jimenez-Del-Rio, Marlene; Sierra-Garcia, Ligia; Lopez-Osorio, Betty; Velez-Pardo, Carlos

    2016-09-01

    D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a water-soluble derivative of natural vitamin E commonly used as a drug delivery agent. Recently, TPGS alone has been reported to induce cell death in lung, breast and prostate cancer. However, the effect of TPGS on cancer cell viability remains unclear. Thus, this study was aimed to evaluate the cytotoxic effect of TPGS on human periphral blood lymphocytes (PBL) and on T cell acute lymphocytic leukemia (ALL) Jurkat clone E6-1 cells and its possible mechanism of action. PBL and Jurkat cells were treated with TPGS (10, 20, 40, 60, and 80 μM), and morphological changes in the cell nucleus, mitochondrial membrane potential (ΔΨm), and intracellular reactive oxygen species levels were determined by immune-fluorescence microscopy and flow cytometry. Cellular apoptosis markers were also evaluated by immunocytochemistry. In this study, TPGS induced apoptotic cell death in Jurkat cells, but not in PBL, in a dose-response manner with increasing nuclear DNA fragmentation, increasing cell cycle arrest, and decreasing ΔΨm. Additionally, TPGS increased dichlorofluorescein fluorescence intensity, indicative of H2O2 production, in a dose-independent fashion. TPGS increased DJ-1 Cys(106)-sulfonate, as a marker of intracellular stress and induced the activation of NF-κB, p53 and c-Jun transcription factors. Additionally, it increased the expression of apoptotic markers Bcl-2 related pro-apoptotic proteins Bax and PUMAand activated caspase-3. The antioxidant N-acetyl-L-cysteine and known pharmacological inhibitors protected the cells from the TPGS induced effects. In conclusion, TPGS selectively induces apoptosis in Jurkat cells through two independent but complementary H2O2-mediated signaling pathways. Our findings support the use of TPGS as a potential treatment for ALL.

  11. Human gastric signet ring carcinoma (KATO-III) cell apoptosis induced by Vitex agnus-castus fruit extract through intracellular oxidative stress.

    Science.gov (United States)

    Ohyama, Kunio; Akaike, Takenori; Imai, Masahiko; Toyoda, Hiroo; Hirobe, Chieko; Bessho, Toshio

    2005-07-01

    We have previously reported that an ethanol extract of the dried ripe fruit of Vitex agnus-castus (Vitex) displays cytotoxic activity against certain kinds of human cancer cell line resulting in the induction of apoptosis. In this paper, we investigate the molecular mechanism of apoptosis induced by Vitex using a human gastric signet ring carcinoma cell line, KATO-III. DNA fragmentation was observed in Vitex-treated KATO-III cells in a time- and dose-dependent manner. DNA fragmentation was accompanied by the following phenomena: elevation in the level of hemeoxygenase-1 protein and thioredoxin reductase mRNA; repression of Mn-superoxide dismutase and catalase mRNAs; release of cytochrome c from mitochondria into the cytosol; activation of caspases-8, -9 and -3; decrease in the level of Bcl-2, Bcl-XL and Bid protein; increase in the level of Bad protein. The intracellular oxidized state, measured using 2',7'-dichlorofluorescin diacetate, increased after Vitex treatment. While the amount of intracellular GSH decreased significantly after treatment with Vitex, the level of GSSG was unaffected. Furthermore, no significant perturbation in the amount of proteins/mRNAs related to glutathione metabolism could be detected. These apoptotic alterations induced by exposure to Vitex were blocked by the presence of an anti-oxidative reagent, N-acetyl-l-cysteine, or the addition of exogenous GSH. Our results demonstrate that intracellular oxidative stress and mitochondrial membrane damage is responsible for Vitex-induced apoptosis, which may be mediated by a diminution of reduced type glutathione within the cell.

  12. Cytotoxicity and apoptotic inducibility of Vitex agnus-castus fruit extract in cultured human normal and cancer cells and effect on growth.

    Science.gov (United States)

    Ohyama, Kunio; Akaike, Takenori; Hirobe, Chieko; Yamakawa, Toshio

    2003-01-01

    A crude extract was prepared with ethanol from dried ripened Vitex agnus-castus fruits growing in Israel (Vitex extract). Cytotoxicity of the extract against human uterine cervical canal fibroblast (HCF), human embryo fibroblast (HE-21), ovarian cancer (MCF-7), cervical carcinoma (SKG-3a), breast carcinoma (SKOV-3), gastric signet ring carcinoma (KATO-III), colon carcinoma (COLO 201), and small cell lung carcinoma (Lu-134-A-H) cells was examined. After culture for 24 h (logarithmic growth phase) or 72 h (stationary growth phase), the cells were treated with various concentrations of Vitex extract. In both growth phases, higher growth activity of cells and more cytotoxic activity of Vitex extract were seen. The cytotoxic activity against stationary growth-phase cells was less than that against logarithmic growth-phase cells. DNA fragmentation of Vitex extract-treated cells was seen in SKOV-3, KATO-III, COLO 201, and Lu-134-A-H cells. The DNA fragmentation in Vitex extract-treated KATO-III cells was inhibited by the presence of the antioxidative reagent pyrrolidine dithiocarbamate or N-acetyl-L-cysteine (NAC). Western blotting analysis showed that in Vitex extract-treated KATO-III cells, the presence of NAC also inhibited the expression of heme oxygenase-1 and the active forms of caspases-3, -8 and -9. It is concluded that the cytotoxic activity of Vitex extract may be attributed to the effect on cell growth, that cell death occurs through apoptosis, and that this apoptotic cell death may be attributed to increased intracellular oxidation by Vitex extract treatment.

  13. Hexavalent chromium induces energy metabolism disturbance and p53-dependent cell cycle arrest via reactive oxygen species in L-02 hepatocytes.

    Science.gov (United States)

    Xiao, Fang; Feng, Xiaotao; Zeng, Ming; Guan, Lan; Hu, Qingqing; Zhong, Caigao

    2012-12-01

    Hexavalent chromium [Cr(VI)] has become a non-negligible pollutant in the world. Cr(VI) exposure leads to severe damage to the liver, but the mechanisms involved in Cr(VI)-mediated toxicity in the liver are unclear. The present study aimed to explore whether Cr(VI) induces energy metabolism disturbance and cell cycle arrest in human L-02 hepatocytes. We showed that Cr(VI) inhibited state 3 respiration, respiratory control rate (RCR), and subsequently induced energy metabolism disturbance with decreased ATP production. Interestingly, cell cycle analysis by flow cytometry and protein expression analysis by western blotting revealed that low dose of Cr(VI) (4 uM) exposure induced S phase cell cycle arrest with decreased mediator of replication checkpoint 1 (Mrc1) and cyclin-dependent kinase 2 (CDK2), while higher doses of Cr(VI) (16, 32 uM) exposure resulted in G2/M phase arrest with decreased budding uninhibited by benzimidazoles-related 1 (BubR1) and cell division cycle 25 (CDC25). Mechanism study revealed that Cr(VI) decreased the activities of mitochondrial respiratory chain complex (MRCC) I and II, thus leading to ROS accumulation. Moreover, inhibiting ROS production by antioxidant N-acetyl-L-cysteine (NAC) rescued Cr(VI)-induced ATP depletion and cell cycle arrest. ROS-mediated p53 activation was found to involve in Cr(VI)-induced cell cycle arrest, and p53 inhibitor Pifithrin-α (PFT-α) rescued Cr(VI)-induced reduction of check point proteins Mrc1 and BubR1, thus inhibiting cell cycle arrest. In summary, the present study provides experimental evidence that Cr(VI) leads to energy metabolism disturbance and p53-dependent cell cycle arrest via ROS in L-02 hepatocytes.

  14. Dieckol, isolated from the edible brown algae Ecklonia cava, induces apoptosis of ovarian cancer cells and inhibits tumor xenograft growth.

    Science.gov (United States)

    Ahn, Ji-Hye; Yang, Yeong-In; Lee, Kyung-Tae; Choi, Jung-Hye

    2015-02-01

    Ecklonia cava is an abundant brown alga and has been reported to possess various bioactive compounds having anti-inflammatory effect. However, the anticancer effects of dieckol, a major active compound in E. cava, are poorly understood. In the present study, we investigated the anti-tumor activity of dieckol and its molecular mechanism in ovarian cancer cells and in a xenograft mouse model . MTT assay, PI staining, and PI and Annexin double staining were performed to study cell cytotoxicity, cell cycle distribution, and apoptosis. We also investigated reactive oxygen species (ROS) production and protein expression using flow cytometry and Western blot analysis, respectively. Anti-tumor effects of dieckol were evaluated in SKOV3 tumor xenograft model. We found that the E. cava extract and its phlorotannins have cytotoxic effects on A2780 and SKOV3 ovarian cancer cells. Dieckol induced the apoptosis of SKOV3 cells and suppressed tumor growth without any significant adverse effect in the SKOV3-bearing mouse model. Dieckol triggered the activation of caspase-8, caspase-9, and caspase-3, and pretreatment with caspase inhibitors neutralized the pro-apoptotic activity of dieckol. Furthermore, treatment with dieckol caused mitochondrial dysfunction and suppressed the levels of anti-apoptotic proteins. We further demonstrated that dieckol induced an increase in intracellular ROS, and the antioxidant N-acetyl-L-cysteine (NAC) significantly reversed the caspase activation, cytochrome c release, Bcl-2 downregulation, and apoptosis that were caused by dieckol. Moreover, dieckol inhibited the activity of AKT and p38, and overexpression of AKT and p38, at least in part, reversed dieckol-induced apoptosis in SKOV3 cells. These data suggest that dieckol suppresses ovarian cancer cell growth by inducing caspase-dependent apoptosis via ROS production and the regulation of AKT and p38 signaling.

  15. Src tyrosine kinase mediates platelet-derived growth factor BB-induced and redox-dependent migration in metanephric mesenchymal cells

    Science.gov (United States)

    Gorin, Yves

    2013-01-01

    The adult kidney is derived from the interaction between the metanephric blastema and the ureteric bud. Platelet-derived growth factor (PDGF) receptor β is essential for the development of the mature glomerular tuft, as mice deficient for this receptor lack mesangial cells. This study investigated the role of Src tyrosine kinase in PDGF-mediated reactive oxygen species (ROS) generation and migration of metanephric mesenchymal cells (MMCs). Cultured embryonic MMCs from wild-type and PDGF receptor-deficient embryos were established. Migration was determined via wound-healing assay. Unlike PDGF AA, PDGF BB-induced greater migration in MMCs with respect to control. This was abrogated by neutralizing an antibody to PDGF BB. Phosphatidylinositol 3-kinase (PI3K) inhibitors suppressed PDGF BB-induced migration. Conversely, mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitors had no effect. Src inhibitors inhibited PDGF-induced cell migration, PI3K activity, and Akt phosphorylation. Adenoviral dominant negative Src (AD DN Src) abrogated PDGF BB-induced Akt phosphorylation. Hydrogen peroxide stimulated cell migration. PDGF BB-induced wound closure was inhibited by the antioxidants N-acetyl-l-cysteine, tiron, and the flavoprotein inhibitor diphenyleneiodonium. These cells express the NADPH oxidase homolog Nox4. Inhibiting Nox4 with antisense oligonucleotides or small interfering RNA (siRNA) suppressed PDGF-induced wound closure. Inhibition of Src with siRNA reduced PDGF BB-induced ROS generation as assessed by 2′,7′-dichlorodihydrofluorescein diacetate fluorescence. Furthermore, PDGF BB-stimulated ROS generation and migration were similarly suppressed by Ad DN Src. In MMCs, PDGF BB-induced migration is mediated by PI3K and Src in a redox-dependent manner involving Nox4. Src may be upstream to PI3K and Nox4. PMID:24197068

  16. Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone Andrographolide, the active component of Andrographis paniculata

    Science.gov (United States)

    Yang, Shuo; Evens, Andrew M.; Prachand, Sheila; Singh, Amareshwar T.K; Bhalla, Savita; David, Kevin; Gordon, Leo I.

    2010-01-01

    Purpose Andrographolide is a diterpenoid lactone isolated from Andrographis paniculata (King of Bitters), an herbal medicine used in Asia. It has been reported to have anti-inflammatory, antihypertensive, anti-viral and immune-stimulant properties. Furthermore, it has been shown to inhibit cancer cell proliferation and induce apoptosis in leukemia and solid tumor cell lines. Experimental Design We studied the Burkitt p53 mutated Ramos cell line, the mantle-cell lymphoma (MCL) line Granta, the follicular lymphoma (FL) cell line HF-1 and the diffuse large B-cell lymphoma (DLBCL) cell line SUDHL4, as well as primary cells from patients with FL, DLBCL, and MCL. Results We found that andrographolide resulted in dose- and time-dependent cell death as measured by MTT. Andrographolide significantly increased reactive oxygen species (ROS) production in all cell lines. To determine mechanism of cell death, we measured apoptosis by Annexin-V/propidium iodide (PI) in the presence and absence of the antioxidant N-acetyl-L-cysteine (NAC), the glutathione-depleting agent buthionine sulfoxamine (BSO), or caspase inhibitors. We found that apoptosis was greatly enhanced by BSO, blocked by NAC, and accompanied by PARP cleavage and activation of caspases 3, 8 and 9. We measured BAX conformational change, and mitochondrial membrane potential, and using mouse embryonic fibroblast (MEF) Bax/Bak double knockouts (MEFBax−/−/Bak−/−), we found that apoptosis was mediated through mitochondrial pathways, but dependent on caspases in both cell lines and in patient samples. Conclusions Andrographolide caused ROS-dependent apoptosis in lymphoma cell lines and in primary tumor samples, which was enhanced by depletion of GSH and inhibited by NAC or the pan-caspase inhibitor Z-VAD-FMK. Further studies of diterpenoid lactones in lymphoma are warranted. PMID:20798229

  17. Induction of apoptosis in renal cell carcinoma by reactive oxygen species: involvement of extracellular signal-regulated kinase 1/2, p38delta/gamma, cyclooxygenase-2 down-regulation, and translocation of apoptosis-inducing factor.

    LENUS (Irish Health Repository)

    Ambrose, Monica

    2012-02-03

    Renal cell carcinoma (RCC) is the most common malignancy of the kidney. Unfortunately, RCCs are highly refractory to conventional chemotherapy, radiation therapy, and even immunotherapy. Thus, novel therapeutic targets need to be sought for the successful treatment of RCCs. We now report that 6-anilino-5,8-quinolinequinone (LY83583), an inhibitor of cyclic GMP production, induced growth arrest and apoptosis of the RCC cell line 786-0. It did not prove deleterious to normal renal epithelial cells, an important aspect of chemotherapy. To address the cellular mechanism(s), we used both genetic and pharmacological approaches. LY83583 induced a time- and dose-dependent increase in RCC apoptosis through dephosphorylation of mitogen-activated protein kinase kinase 1\\/2 and its downstream extracellular signal-regulated kinases (ERK) 1 and -2. In addition, we observed a decrease in Elk-1 phosphorylation and cyclooxygenase-2 (COX-2) down-regulation. We were surprised that we failed to observe an increase in either c-Jun NH(2)-terminal kinase or p38alpha and -beta mitogen-activated protein kinase activation. In contradiction, reintroduction of p38delta by stable transfection or overexpression of p38gamma dominant negative abrogated the apoptotic effect. Cell death was associated with a decrease and increase in Bcl-x(L) and Bax expression, respectively, as well as release of cytochrome c and translocation of apoptosis-inducing factor. These events were associated with an increase in reactive oxygen species formation. The antioxidant N-acetyl l-cysteine, however, opposed LY83583-mediated mitochondrial dysfunction, ERK1\\/2 inactivation, COX-2 down-regulation, and apoptosis. In conclusion, our results suggest that LY83583 may represent a novel therapeutic agent for the treatment of RCC, which remains highly refractory to antineoplastic agents. Our data provide a molecular basis for the anticancer activity of LY83583.

  18. Nuclear DAMP complex-mediated RAGE-dependent macrophage cell death

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ruochan [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Fu, Sha; Fan, Xue-Gong [Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Lotze, Michael T.; Zeh, Herbert J. [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Tang, Daolin, E-mail: tangd2@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Kang, Rui, E-mail: kangr@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States)

    2015-03-13

    High mobility group box 1 (HMGB1), histone, and DNA are essential nuclear components involved in the regulation of chromosome structure and function. In addition to their nuclear function, these molecules act as damage-associated molecular patterns (DAMPs) alone or together when released extracellularly. The synergistic effect of these nuclear DNA-HMGB1-histone complexes as DAMP complexes (nDCs) on immune cells remains largely unexplored. Here, we demonstrate that nDCs limit survival of macrophages (e.g., RAW264.7 and peritoneal macrophages) but not cancer cells (e.g., HCT116, HepG2 and Hepa1-6). nDCs promote production of inflammatory tumor necrosis factor α (TNFα) release, triggering reactive oxygen species-dependent apoptosis and necrosis. Moreover, the receptor for advanced glycation end products (RAGE), but not toll-like receptor (TLR)-4 and TLR-2, was required for Akt-dependent TNFα release and subsequent cell death following treatment with nDCs. Genetic depletion of RAGE by RNAi, antioxidant N-Acetyl-L-cysteine, and TNFα neutralizing antibody significantly attenuated nDC-induced cell death. These findings provide evidence supporting novel signaling mechanisms linking nDCs and inflammation in macrophage cell death. - Highlights: • Nuclear DAMP complexes (nDCs) selectively induce cell death in macrophages, but not cancer cells. • TNFα-mediated oxidative stress is required for nDC-induced death. • RAGE-mediated Akt activation is required for nDC-induced TNFα release. • Blocking RAGE and TNFα inhibits nDC-induced macrophage cell death.

  19. Treatments for Biomedical Abnormalities Associated with Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Richard Eugene Frye

    2014-06-01

    Full Text Available Recent studies point to the effectiveness of novel treatments that address physiological abnormalities associated with autism spectrum disorder (ASD. This is significant because safe and effective treatments for ASD remain limited. These physiological abnormalities as well as studies addressing treatments of these abnormalities are reviewed in this article. Treatments commonly used to treat mitochondrial disease have been found to improve both core and associated ASD symptoms. Double-blind, placebo-controlled studies have investigated L-carnitine and a multivitamin containing B vitamins, antioxidants, vitamin E, and coenzyme Q10 while non-blinded studies have investigated ubiquinol. Controlled and uncontrolled studies using folinic acid, a reduced form of folate, have reported marked improvements in core and associated ASD symptoms in some children with ASD and folate related pathways abnormities. Treatments that could address redox metabolism abnormalities include methylcobalamin with and without folinic acid in open-label studies and vitamin C and N-acetyl-L-cysteine in double-blind, placebo-controlled studies. These studies have reported improved core and associated symptoms with these treatments. Lastly, both open-label and double-blind, placebo-controlled studies have reported improvement in core and associated ASD symptoms with tetrahydrobiopterin. Overall, these treatments were generally well tolerated without significant adverse effects for most children, although we review the reported adverse effects in detail. This review provides evidence for potential safe and effective treatments for core and associated symptoms of ASD that target underlying known physiological abnormalities associated with ASD. Further research is needed to define subgroups of children with ASD in which these treatments may be most effective as well as confirm their efficacy in double-blind, placebo-controlled, large-scale multicenter studies.

  20. Helium generated cold plasma finely regulates activation of human fibroblast-like primary cells.

    Directory of Open Access Journals (Sweden)

    Paola Brun

    Full Text Available Non-thermal atmospheric pressure plasmas are being developed for a wide range of health care applications, including wound healing. However in order to exploit the potential of plasma for clinical applications, the understanding of the mechanisms involved in plasma-induced activation of fibroblasts, the cells active in the healing process, is mandatory. In this study, the role of helium generated plasma in the tissue repairing process was investigated in cultured human fibroblast-like primary cells, and specifically in hepatic stellate cells and intestinal subepithelial myofibroblasts. Five minutes after treatment, plasma induced formation of reactive oxygen species (ROS in cultured cells, as assessed by flow cytometric analysis of fluorescence-activated 2',7'-dichlorofluorescein diacetate probe. Plasma-induced intracellular ROS were characterized by lower concentrations and shorter half-lives with respect to hydrogen peroxide-induced ROS. Moreover ROS generated by plasma treatment increased the expression of peroxisome proliferator activated receptor (PPAR-γ, nuclear receptor that modulates the inflammatory responses. Plasma exposure promoted wound healing in an in vitro model and induced fibroblast migration and proliferation, as demonstrated, respectively, by trans-well assay and partitioning between daughter cells of carboxyfluorescein diacetate succinimidyl ester fluorescent dye. Plasma-induced fibroblast migration and proliferation were found to be ROS-dependent as cellular incubation with antioxidant agents (e.g. N-acetyl L-cysteine cancelled the biological effects. This study provides evidence that helium generated plasma promotes proliferation and migration in liver and intestinal fibroblast-like primary cells mainly by increasing intracellular ROS levels. Since plasma-evoked ROS are time-restricted and elicit the PPAR-γ anti-inflammatory molecular pathway, this strategy ensures precise regulation of human fibroblast activation and

  1. PARP-1 modulation of mTOR signaling in response to a DNA alkylating agent.

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    Chantal Ethier

    Full Text Available Poly(ADP-ribose polymerase-1 (PARP-1 is widely involved in cell death responses. Depending on the degree of injury and on cell type, PARP activation may lead to autophagy, apoptosis or necrosis. In HEK293 cells exposed to the alkylating agent N-methyl-N'-nitro-N'-nitrosoguanine (MNNG, we show that PARP-1 activation triggers a necrotic cell death response. The massive poly(ADP-ribose (PAR synthesis following PARP-1 activation leads to the modulation of mTORC1 pathway. Shortly after MNNG exposure, NAD⁺ and ATP levels decrease, while AMP levels drastically increase. We characterized at the molecular level the consequences of these altered nucleotide levels. First, AMP-activated protein kinase (AMPK is activated and the mTORC1 pathway is inhibited by the phosphorylation of Raptor, in an attempt to preserve cellular energy. Phosphorylation of the mTORC1 target S6 is decreased as well as the phosphorylation of the mTORC2 component Rictor on Thr1135. Finally, Akt phosphorylation on Ser473 is lost and then, cell death by necrosis occurs. Inhibition of PARP-1 with the potent PARP inhibitor AG14361 prevents all of these events. Moreover, the antioxidant N-acetyl-L-cysteine (NAC can also abrogate all the signaling events caused by MNNG exposure suggesting that reactive oxygen species (ROS production is involved in PARP-1 activation and modulation of mTOR signaling. In this study, we show that PARP-1 activation and PAR synthesis affect the energetic status of cells, inhibit the mTORC1 signaling pathway and possibly modulate the mTORC2 complex affecting cell fate. These results provide new evidence that cell death by necrosis is orchestrated by the balance between several signaling pathways, and that PARP-1 and PAR take part in these events.

  2. Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone andrographolide, the active component of Andrographis paniculata.

    Science.gov (United States)

    Yang, Shuo; Evens, Andrew M; Prachand, Sheila; Singh, Amareshwar T K; Bhalla, Savita; David, Kevin; Gordon, Leo I

    2010-10-01

    Andrographolide is a diterpenoid lactone isolated from Andrographis paniculata (King of Bitters), an herbal medicine used in Asia. It has been reported to have anti-inflammatory, antihypertensive, antiviral, and immune-stimulant properties. Furthermore, it has been shown to inhibit cancer cell proliferation and induce apoptosis in leukemia and solid tumor cell lines. We studied the Burkitt p53-mutated Ramos cell line, the mantle cell lymphoma (MCL) line Granta, the follicular lymphoma (FL) cell line HF-1, and the diffuse large B-cell lymphoma (DLBCL) cell line SUDHL4, as well as primary cells from patients with FL, DLBCL, and MCL. We found that andrographolide resulted in dose- and time-dependent cell death as measured by MTT. Andrographolide significantly increased reactive oxygen species (ROS) production in all cell lines. To determine mechanism of cell death, we measured apoptosis by Annexin V/propidium iodide in the presence and absence of the antioxidant N-acetyl-l-cysteine (NAC), the glutathione (GSH)-depleting agent buthionine sulfoxamine (BSO), or caspase inhibitors. We found that apoptosis was greatly enhanced by BSO, blocked by NAC, and accompanied by poly(ADP-ribose) polymerase cleavage and activation of caspase-3, caspase-8, and caspase-9. We measured BAX conformational change and mitochondrial membrane potential, and using mouse embryonic fibroblast (MEF) Bax/Bak double knockouts (MEF(Bax-/-/Bak-/-)), we found that apoptosis was mediated through mitochondrial pathways, but dependent on caspases in both cell lines and patient samples. Andrographolide caused ROS-dependent apoptosis in lymphoma cell lines and in primary tumor samples, which was enhanced by depletion of GSH and inhibited by NAC or the pan-caspase inhibitor Z-VAD-FMK. Further studies of diterpenoid lactones in lymphoma are warranted. ©2010 AACR.

  3. 1800MHz Microwave Induces p53 and p53-Mediated Caspase-3 Activation Leading to Cell Apoptosis In Vitro.

    Directory of Open Access Journals (Sweden)

    Fuqiang Xing

    Full Text Available Recent studies have reported that exposure of mammalian cells to microwave radiation may have adverse effects such as induction of cell apoptosis. However, the molecular mechanisms underlying microwave induced mammalian cell apoptosis are not fully understood. Here, we report a novel mechanism: exposure to 1800MHz microwave radiation induces p53-dependent cell apoptosis through cytochrome c-mediated caspase-3 activation pathway. We first measured intensity of microwave radiation from several electronic devices with an irradiation detector. Mouse NIH/3T3 and human U-87 MG cells were then used as receivers of 1800MHz electromagnetic radiation (EMR at a power density of 1209 mW/m2. Following EMR exposure, cells were analyzed for viability, intracellular reactive oxygen species (ROS generation, DNA damage, p53 expression, and caspase-3 activity. Our analysis revealed that EMR exposure significantly decreased viability of NIH/3T3 and U-87 MG cells, and increased caspase-3 activity. ROS burst was observed at 6 h and 48 h in NIH/3T3 cells, while at 3 h in U-87 MG cells. Hoechst 33258 staining and in situ TUNEL assay detected that EMR exposure increased DNA damage, which was significantly restrained in the presence of N-acetyl-L-cysteine (NAC, an antioxidant. Moreover, EMR exposure increased the levels of p53 protein and p53 target gene expression, promoted cytochrome c release from mitochondrion, and increased caspase-3 activity. These events were inhibited by pretreatment with NAC, pifithrin-α (a p53 inhibitor and caspase inhibitor. Collectively, our findings demonstrate, for the first time, that 1800MHz EMR induces apoptosis-related events such as ROS burst and more oxidative DNA damage, which in turn promote p53-dependent caspase-3 activation through release of cytochrome c from mitochondrion. These findings thus provide new insights into physiological mechanisms underlying microwave-induced cell apoptosis.

  4. 1800MHz Microwave Induces p53 and p53-Mediated Caspase-3 Activation Leading to Cell Apoptosis In Vitro

    Science.gov (United States)

    Xing, Fuqiang; Zhan, Qiuqiang; He, Yiduo; Cui, Jiesheng; He, Sailing; Wang, Guanyu

    2016-01-01

    Recent studies have reported that exposure of mammalian cells to microwave radiation may have adverse effects such as induction of cell apoptosis. However, the molecular mechanisms underlying microwave induced mammalian cell apoptosis are not fully understood. Here, we report a novel mechanism: exposure to 1800MHz microwave radiation induces p53-dependent cell apoptosis through cytochrome c-mediated caspase-3 activation pathway. We first measured intensity of microwave radiation from several electronic devices with an irradiation detector. Mouse NIH/3T3 and human U-87 MG cells were then used as receivers of 1800MHz electromagnetic radiation (EMR) at a power density of 1209 mW/m2. Following EMR exposure, cells were analyzed for viability, intracellular reactive oxygen species (ROS) generation, DNA damage, p53 expression, and caspase-3 activity. Our analysis revealed that EMR exposure significantly decreased viability of NIH/3T3 and U-87 MG cells, and increased caspase-3 activity. ROS burst was observed at 6 h and 48 h in NIH/3T3 cells, while at 3 h in U-87 MG cells. Hoechst 33258 staining and in situ TUNEL assay detected that EMR exposure increased DNA damage, which was significantly restrained in the presence of N-acetyl-L-cysteine (NAC, an antioxidant). Moreover, EMR exposure increased the levels of p53 protein and p53 target gene expression, promoted cytochrome c release from mitochondrion, and increased caspase-3 activity. These events were inhibited by pretreatment with NAC, pifithrin-α (a p53 inhibitor) and caspase inhibitor. Collectively, our findings demonstrate, for the first time, that 1800MHz EMR induces apoptosis-related events such as ROS burst and more oxidative DNA damage, which in turn promote p53-dependent caspase-3 activation through release of cytochrome c from mitochondrion. These findings thus provide new insights into physiological mechanisms underlying microwave-induced cell apoptosis. PMID:27689798

  5. Nano-Scaled Particles of Titanium Dioxide Convert Benign Mouse Fibrosarcoma Cells into Aggressive Tumor Cells

    Science.gov (United States)

    Onuma, Kunishige; Sato, Yu; Ogawara, Satomi; Shirasawa, Nobuyuki; Kobayashi, Masanobu; Yoshitake, Jun; Yoshimura, Tetsuhiko; Iigo, Masaaki; Fujii, Junichi; Okada, Futoshi

    2009-01-01

    Nanoparticles are prevalent in both commercial and medicinal products; however, the contribution of nanomaterials to carcinogenesis remains unclear. We therefore examined the effects of nano-sized titanium dioxide (TiO2) on poorly tumorigenic and nonmetastatic QR-32 fibrosarcoma cells. We found that mice that were cotransplanted subcutaneously with QR-32 cells and nano-sized TiO2, either uncoated (TiO2−1, hydrophilic) or coated with stearic acid (TiO2−2, hydrophobic), did not form tumors. However, QR-32 cells became tumorigenic after injection into sites previously implanted with TiO2−1, but not TiO2−2, and these developing tumors acquired metastatic phenotypes. No differences were observed either histologically or in inflammatory cytokine mRNA expression between TiO2−1 and TiO2−2 treatments. However, TiO2−2, but not TiO2−1, generated high levels of reactive oxygen species (ROS) in cell-free conditions. Although both TiO2−1 and TiO2−2 resulted in intracellular ROS formation, TiO2−2 elicited a stronger response, resulting in cytotoxicity to the QR-32 cells. Moreover, TiO2−2, but not TiO2−1, led to the development of nuclear interstices and multinucleate cells. Cells that survived the TiO2 toxicity acquired a tumorigenic phenotype. TiO2-induced ROS formation and its related cell injury were inhibited by the addition of antioxidant N-acetyl-l-cysteine. These results indicate that nano-sized TiO2 has the potential to convert benign tumor cells into malignant ones through the generation of ROS in the target cells. PMID:19815711

  6. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lingzhi; Qiu, Ping; Chen, Bailing; Lu, Yongju; Wu, Kai; Thakur, Chitra; Chang, Qingshan; Sun, Jiaying; Chen, Fei, E-mail: fchen@wayne.edu

    2014-05-01

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H{sub 2}O{sub 2}, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H{sub 2}O{sub 2}. Furthermore, both arsenic and H{sub 2}O{sub 2} were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As{sup 3+}) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As{sup 3+}-induced EZH2 phosphorylation. • As{sup 3+} induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm.

  7. Activation of the NRF2-ARE signalling pathway by the Lentinula edodes polysaccharose LNT alleviates ROS-mediated cisplatin nephrotoxicity.

    Science.gov (United States)

    Chen, Qian; Peng, Huixia; Dong, Lei; Chen, Lijuan; Ma, Xiaobin; Peng, Yuping; Dai, Shejiao; Liu, Qiang

    2016-07-01

    The nephrotoxicity of cisplatin (cis-DDP) limits its general clinical applications. Lentinan (LNT), a dextran extracted from the mushroom Lentinula edodes, has been shown to have multiple pharmacological activities. The primary objective of the current study was to determine whether and how LNT alleviates cis-DDP- induced cytotoxicity in HK-2 cells and nephrotoxicity in mice. LNT did not interfere with cisplatin's anti-tumour efficacy in vitro and functioned cooperatively with cis-DDP to inhibit activity in HeLa and A549 tumour cells. LNT alleviated the cis-DDP-induced decrease in HK-2 cell viability, caspase-3 activation and cleavage of the DNA repair enzyme PARP, decreased HK-2 cell apoptosis and inhibited reactive oxygen species (ROS) accumulation in HK-2 cells. The inhibitor of ROS (N-acetyl-L-cysteine, NAC) could decreased the apoptosis of HK-2 cell. In addition, LNT significantly prevented cis-DDP-induced kidney injury in vivo. LNT itself could not eliminate ROS levels in vitro. Further studies demonstrated that LNT induced NF-E2 p45-related factor 2 (Nrf2) protein and mRNA expression in a time- and dose-dependent manner. LNT promoted Nrf2 translocation to the nucleus and binding to the antioxidant-response element (ARE) sequence and induced the transcription and translation of heme oxygenase 1 (HO-1), aldo-keto reductases 1C1 and 1C2 (AKR1C), and NADP(H):quinone oxidoreductase 1 (NQO1). Finally, we used hNrf2 siRNA and an Nrf2 agonist (tBHQ) to inhibit or enhance Nrf2 expression. The results demonstrated that the LNT-mediated alleviation of cis-DDP-induced nephrotoxicity was achieved by preventing the accumulation of ROS in a manner that depended on the activation of the Nrf2-ARE signalling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Nano-scaled particles of titanium dioxide convert benign mouse fibrosarcoma cells into aggressive tumor cells.

    Science.gov (United States)

    Onuma, Kunishige; Sato, Yu; Ogawara, Satomi; Shirasawa, Nobuyuki; Kobayashi, Masanobu; Yoshitake, Jun; Yoshimura, Tetsuhiko; Iigo, Masaaki; Fujii, Junichi; Okada, Futoshi

    2009-11-01

    Nanoparticles are prevalent in both commercial and medicinal products; however, the contribution of nanomaterials to carcinogenesis remains unclear. We therefore examined the effects of nano-sized titanium dioxide (TiO(2)) on poorly tumorigenic and nonmetastatic QR-32 fibrosarcoma cells. We found that mice that were cotransplanted subcutaneously with QR-32 cells and nano-sized TiO(2), either uncoated (TiO(2)-1, hydrophilic) or coated with stearic acid (TiO(2)-2, hydrophobic), did not form tumors. However, QR-32 cells became tumorigenic after injection into sites previously implanted with TiO(2)-1, but not TiO(2)-2, and these developing tumors acquired metastatic phenotypes. No differences were observed either histologically or in inflammatory cytokine mRNA expression between TiO(2)-1 and TiO(2)-2 treatments. However, TiO(2)-2, but not TiO(2)-1, generated high levels of reactive oxygen species (ROS) in cell-free conditions. Although both TiO(2)-1 and TiO(2)-2 resulted in intracellular ROS formation, TiO(2)-2 elicited a stronger response, resulting in cytotoxicity to the QR-32 cells. Moreover, TiO(2)-2, but not TiO(2)-1, led to the development of nuclear interstices and multinucleate cells. Cells that survived the TiO(2) toxicity acquired a tumorigenic phenotype. TiO(2)-induced ROS formation and its related cell injury were inhibited by the addition of antioxidant N-acetyl-l-cysteine. These results indicate that nano-sized TiO(2) has the potential to convert benign tumor cells into malignant ones through the generation of ROS in the target cells.

  9. Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species.

    Directory of Open Access Journals (Sweden)

    Szu-Ying Wu

    Full Text Available BACKGROUND: The aim of this study was to determine the molecular mechanisms of physalin F, an effective purified extract of Physalis angulata L. (Solanacae, in renal carcinoma A498 cells. METHODOLOGY/PRINCIPAL FINDINGS: Physalin F was observed to significantly induce cytotoxicity of three human renal carcinoma A498, ACHN, and UO-31 cells in a concentration-dependent manner; this was especially potent in A498 cells. The physalin F-induced cell apoptosis of A498 cells was characterized by MTT assay, nuclear DNA fragmentation and chromatin condensation. Using flow cytometry analysis, physalin F induced A498 cell apoptosis as demonstrated by the accumulation of the sub-G1 phase in a concentration- and time-dependent manner. Moreover, physalin F-mediated accumulation of reactive oxygen species (ROS caused Bcl-2 family proteins, Bcl-2, and Bcl-xL degradation, which led to disruption of mitochondrial membrane potential and release of cytochrome c from the mitochondria into the cytosol. These effects were associated with induction of caspase-3 and caspase-9 activity, which led to poly(ADP-ribose polymerase cleavage. However, the antioxidant N-acetyl-(L-cysteine (NAC and glutathione (GSH resulted in the inhibition of these events and reversed physalin F-induced cell apoptosis. In addition, physalin F suppressed NF-κB activity and nuclear translocation of p65 and p50, which was reversed by NAC and GSH. CONCLUSION: Physalin F induced cell apoptosis through the ROS-mediated mitochondrial pathway and suppressed NF-κB activation in human renal cancer A498 cells. Thus, physalin F appears to be a promising anti-cancer agent worthy of further clinical development.

  10. Effects of cigarette smoke condensate on proliferation and wound closure of bronchial epithelial cells in vitro: role of glutathione

    Directory of Open Access Journals (Sweden)

    Rabe Klaus F

    2005-11-01

    Full Text Available Abstract Background Increased airway epithelial proliferation is frequently observed in smokers. To elucidate the molecular mechanisms leading to these epithelial changes, we studied the effect of cigarette smoke condensate (CSC on cell proliferation, wound closure and mitogen activated protein kinase (MAPK activation. We also studied whether modulation of intracellular glutathione/thiol levels could attenuate CSC-induced cell proliferation. Methods Cells of the bronchial epithelial cell line NCI-H292 and subcultures of primary bronchial epithelial cells were used for the present study. The effect of CSC on epithelial proliferation was assessed using 5-bromo-2-deoxyuridine (BrdU incorporation. Modulation of epithelial wound repair was studied by analysis of closure of 3 mm circular scrape wounds during 72 hours of culture. Wound closure was calculated from digital images obtained at 24 h intervals. Activation of mitogen-activated protein kinases was assessed by Western blotting using phospho-specific antibodies. Results At low concentrations CSC increased proliferation of NCI-H292 cells, whereas high concentrations were inhibitory as a result of cytotoxicity. Low concentrations of CSC also increased epithelial wound closure of both NCI-H292 and PBEC, whereas at high concentrations closure was inhibited. At low, mitogenic concentrations, CSC caused persistent activation of ERK1/2, a MAPK involved in cell proliferation. Inhibition of cell proliferation by high concentrations of CSC was associated with activation of the pro-apoptotic MAP kinases p38 and JNK. Modulation of intracellular glutathione (GSH/thiol levels using N-acetyl-L-cysteine, GSH or buthionine sulphoximine (BSO, demonstrated that both the stimulatory and the inhibitory effects of CSC were regulated in part by intracellular GSH levels. Conclusion These results indicate that CSC may increase cell proliferation and wound closure dependent on the local concentration of cigarette smoke

  11. Implication of Glutathione in the In Vitro Antiplasmodial Mechanism of Action of Ellagic Acid

    Science.gov (United States)

    Njomnang Soh, Patrice; Witkowski, Benoit; Gales, Amandine; Huyghe, Eric; Berry, Antoine

    2012-01-01

    The search for new antimalarial chemotherapy has become increasingly urgent due to parasite resistance to current drugs. Ellagic acid (EA) is a polyphenol, recently found in various plant products, that has effective antimalarial activity in vitro and in vivo without toxicity. To further understand the antimalarial mechanism of action of EA in vitro, we evaluated the effects of EA, ascorbic acid and N-acetyl-L-cysteine (NAC), alone and/or in combination on the production of reactive oxygen species (ROS) during the trophozoite and schizonte stages of the erythrocytic cycle of P. falciparum. The parasitized erythrocytes were pre-labelled with DCFDA (dichlorofluorescein diacetate). We showed that NAC had no effect on ROS production, contrary to ascorbic acid and EA, which considerably reduced ROS production. Surprisingly, EA reduced the production of the ROS with concentrations (6.6×10−9 − 6.6×10−6 M) ten-fold lower than ascorbic acid (113×10−6 M). Additionally, the in vitro drug sensitivity of EA with antioxidants showed that antiplasmodial activity is independent of the ROS production inside parasites, which was confirmed by the additive activity of EA and desferrioxamine. Finally, EA could act by reducing the glutathione content inside the Plasmodium parasite. This was consolidated by the decrease in the antiplasmodial efficacy of EA in the murine model Plasmodium yoelii- high GSH strain, known for its high glutathione content. Given its low toxicity and now known mechanism of action, EA appears as a promising antiplasmodial compound. PMID:23029306

  12. MRP-1 and BCRP Promote the Externalization of Phosphatidylserine in Oxalate-treated Renal Epithelial Cells: Implications for Calcium Oxalate Urolithiasis.

    Science.gov (United States)

    Li, YiFu; Yu, ShiLiang; Gan, XiuGuo; Zhang, Ze; Wang, Yan; Wang, YingWei; An, RuiHua

    2017-09-01

    To investigate the possible involvement of multidrug resistance-associated protein 1 (MRP-1) and breast cancer resistance protein (BCRP) in the oxalate-induced redistribution of phosphatidylserine (PS) in renal epithelial cell membranes. A western blot analysis was used to examine the MRP-1 and BCRP expression levels. Surface-expressed PS was detected by the annexin V-binding assay. The cell-permeable fluorogenic probe 2,7-dichlorofluorescein diacetate was used to measure the intracellular reactive oxygen species (ROS) level. A rat model of hyperoxaluria was obtained using 0.5% ethylene glycol and 1.0% ammonium chloride. In addition, certain animals received verapamil (50 mg/kg body weight), which is a common inhibitor of MRP-1 and BCRP. The degree of nephrolithiasis was assessed histomorphometrically using sections stained by Pizzolato method and by measuring the calcium oxalate crystal content in the renal tissue. Oxalate produced a concentration-dependent increase in the synthesis of MRP-1 and BCRP. Treatment with MK571 and Ko143 (MRP-1- and BCRP-specific inhibitors, respectively) significantly attenuated the oxalate-induced PS externalization. Adding the antioxidant N-acetyl-l-cysteine significantly reduced MRP-1 and BCRP expression. In vivo, markedly decreased nephrocalcinosis was observed compared with that in the rat model of hyperoxaluria without verapamil treatment. Oxalate induces the upregulation of MRP-1 and BCRP, which act as phospholipid floppases causing PS externalization in the renal epithelial cell membrane. The process is mediated by intracellular ROS production. The ROS-mediated increase in the synthesis of MRP-1 and BCRP can play an important role in hyperoxaluria-promoted calcium oxalate urolithiasis by facilitating phosphatidylserine redistribution in renal epithelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The flavones apigenin and luteolin induce FOXO1 translocation but inhibit gluconeogenic and lipogenic gene expression in human cells.

    Directory of Open Access Journals (Sweden)

    Christiane Bumke-Vogt

    Full Text Available The flavones apigenin (4',5,7,-trihydroxyflavone and luteolin (3',4',5,7,-tetrahydroxyflavone are plant secondary metabolites with antioxidant, antiinflammatory, and anticancer activities. We evaluated their impact on cell signaling pathways related to insulin-resistance and type 2 diabetes. Apigenin and luteolin were identified in our U-2 OS (human osteosarcoma cell screening assay for micronutrients triggering rapid intracellular translocation of the forkhead box transcription factor O1 (FOXO1, an important mediator of insulin signal transduction. Insulin reversed the translocation of FOXO1 as shown by live cell imaging. The impact on the expression of target genes was evaluated in HepG2 (human hepatoma cells. The mRNA-expression of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK and glucose-6-phosphatase (G6Pc, the lipogenic enzymes fatty-acid synthase (FASN and acetyl-CoA-carboxylase (ACC were down-regulated by both flavones with smaller effective dosages of apigenin than for luteolin. PKB/AKT-, PRAS40-, p70S6K-, and S6-phosphorylation was reduced by apigenin and luteolin but not that of the insulin-like growth factor receptor IGF-1R by apigenin indicating a direct inhibition of the PKB/AKT-signaling pathway distal to the IGF-1 receptor. N-acetyl-L-cysteine did not prevent FOXO1 nuclear translocation induced by apigenin and luteolin, suggesting that these flavones do not act via oxidative stress. The roles of FOXO1, FOXO3a, AKT, sirtuin1 (SIRT1, and nuclear factor (erythroid-derived2-like2 (NRF2, investigated by siRNA knockdown, showed differential patterns of signal pathways involved and a role of NRF2 in the inhibition of gluconeogenic enzyme expression. We conclude that these flavones show an antidiabetic potential due to reduction of gluconeogenic and lipogenic capacity despite inhibition of the PKB/AKT pathway which justifies detailed investigation in vivo.

  14. Atmospheric-Pressure Cold Plasma Induces Transcriptional Changes in Ex Vivo Human Corneas.

    Directory of Open Access Journals (Sweden)

    Umberto Rosani

    Full Text Available Atmospheric pressure cold plasma (APCP might be considered a novel tool for tissue disinfection in medicine since the active chemical species produced by low plasma doses, generated by ionizing helium gas in air, induces reactive oxygen species (ROS that kill microorganisms without substantially affecting human cells.In this study, we evaluated morphological and functional changes in human corneas exposed for 2 minutes (min to APCP and tested if the antioxidant n-acetyl l-cysteine (NAC was able to inhibit or prevent damage and cell death.Immunohistochemistry and western blotting analyses of corneal tissues collected at 6 hours (h post-APCP treatment demonstrated no morphological tissue changes, but a transient increased expression of OGG1 glycosylase that returned to control levels in 24 h. Transcriptome sequencing and quantitative real time PCR performed on different corneas revealed in the treated corneas many differentially expressed genes: namely, 256 and 304 genes showing expression changes greater than ± 2 folds in the absence and presence of NAC, respectively. At 6 h post-treatment, the most over-expressed gene categories suggested an active or enhanced cell functioning, with only a minority of genes specifically concerning oxidative DNA damage and repair showing slight over-expression values (<2 folds. Moreover, time-related expression analysis of eight genes up-regulated in the APCP-treated corneas overall demonstrated the return to control expression levels after 24 h.These findings of transient oxidative stress accompanied by wide-range transcriptome adjustments support the further development of APCP as an ocular disinfectant.

  15. Antioxidant and androgenic effects of dietary ginger on reproductive function of male diabetic rats.

    Science.gov (United States)

    Ghlissi, Zohra; Atheymen, Rim; Boujbiha, Mouhamed Ali; Sahnoun, Zouheir; Makni Ayedi, Fatma; Zeghal, Khaled; El Feki, Abdelfattah; Hakim, Ahmed

    2013-12-01

    This study evaluated the antioxidant and androgenic properties of ginger roots on the reproductive function of male diabetic rats. Animals were divided into three groups; the control (Control), diabetic (Diab) and diabetic fed with dietary ginger for 30 d (Diab + Z). Thereafter, blood samples were collected and reproductive organs (testis, epididymis, prostate and seminal vesicle) were removed for determination of sperm parameters, malondialdehyde (MDA) level, glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and aspartate and lactate aminotransferase (AST and ALT) activities. Dietary ginger decreased blood glucose and MDA level, increased reproductive organ weights and testosterone level, improved semen quantity and motility, and ameliorated the SOD, CAT and GPx activities as well as testis AST, ALT, LDH and ALP activities. Intake of ginger roots improves the antioxidant and androgenic reproductive function of male diabetic rats in addition to its antidiabetic property.

  16. Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome

    DEFF Research Database (Denmark)

    Jepsen, S; Herlevsen, P; Knudsen, P

    1992-01-01

    OBJECTIVE: To examine whether the antioxidant N-acetylcysteine could ameliorate the course of the adult respiratory distress syndrome (ARDS) in man. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Medical and surgical ICU in a regional hospital. PATIENTS: Sixty-six ICU patients...... with ARDS. INTERVENTIONS: Patients with ARDS (PaO2/FiO2 ratio less than 250 torr) were treated with either the antioxidant N-acetylcysteine 150 mg/kg as a loading dose and then 20 mg/kg/hr, or with placebo for 6 days. MEASUREMENTS AND MAIN RESULTS: No improvement could be demonstrated in the PaO2/FiO2 ratio...

  17. Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation.

    Science.gov (United States)

    Sakai, Daisuke; Dixon, Jill; Achilleos, Annita; Dixon, Michael; Trainor, Paul A

    2016-01-21

    Craniofacial anomalies account for approximately one-third of all birth defects and are a significant cause of infant mortality. Since the majority of the bones, cartilage and connective tissues that comprise the head and face are derived from a multipotent migratory progenitor cell population called the neural crest, craniofacial disorders are typically attributed to defects in neural crest cell development. Treacher Collins syndrome (TCS) is a disorder of craniofacial development and although TCS arises primarily through autosomal dominant mutations in TCOF1, no clear genotype-phenotype correlation has been documented. Here we show that Tcof1 haploinsufficiency results in oxidative stress-induced DNA damage and neuroepithelial cell death. Consistent with this discovery, maternal treatment with antioxidants minimizes cell death in the neuroepithelium and substantially ameliorates or prevents the pathogenesis of craniofacial anomalies in Tcof1(+/-) mice. Thus maternal antioxidant dietary supplementation may provide an avenue for protection against the pathogenesis of TCS and similar neurocristopathies.

  18. Antioxidant effects of proanthocyanidin from grape seed on hepatic tissue injury in diabetic rats.

    Science.gov (United States)

    Mansouri, Esrafil; Khorsandi, Layasadat; Abedi, Hassan Ali

    2014-06-01

    Diabetes plays an important role in the induction of the liver injury. Grape seed proanthocyanidin (GSP) have a wide range of medicinal properties against oxidative stress. In this study we evaluated antioxidant effects of GSP on liver in streptozotocin-induced diabetic rats. Thirty male Sprague-Dawley rats were divided into three groups: control, untreated diabetic and diabetic rats treated with GSP. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (50 mg/kg). GSP were administered via oral gavage (200 mg/kg) for 4 weeks. GSP produced significant hepatoprotective effects by decreasing activities of serum aminotransferases and alkaline phosphatase, and decreasing liver malondialdehyde and bilirubin (PGSP significantly ameliorated structural changes induced in liver of diabetic rats. GSP have protective effects against hepatic tissue injury due to antioxidant properties.

  19. Quality and antioxidant properties on sweet cherries as affected by preharvest salicylic and acetylsalicylic acids treatments.

    Science.gov (United States)

    Giménez, María José; Valverde, Juan Miguel; Valero, Daniel; Guillén, Fabián; Martínez-Romero, Domingo; Serrano, María; Castillo, Salvador

    2014-10-01

    The effects of salicylic acid (SA) or acetylsalicylic acid (ASA) treatments during on-tree cherry growth and ripening on fruit quality attributes, especially those related with the content on bioactive compounds and antioxidant activity were analysed in this research. For this purpose, two sweet cherry cultivars, 'Sweet Heart' and 'Sweet Late', were used and SA or ASA treatments, at 0.5, 1.0 and 2.0mM concentrations, were applied at three key points of fruit development (pit hardening, initial colour changes and onset of ripening). These treatments increased fruit weight and ameliorated quality attributes at commercial harvest, and led to cherries with higher concentration in total phenolics and in total anthocyanins, as well as higher antioxidant activity, in both hydrophilic and lipophilic fractions. Thus, preharvest treatments with SA or ASA could be promising tools to improve sweet cherry quality and health beneficial effects for consumers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Biochar from commercially cultivated seaweed for soil amelioration

    OpenAIRE

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-01-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum ? brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma ? red seaweeds). While there is some variability in biochar properties as ...

  1. No Evidence of Racial Differences in Endothelial Function and Exercise Blood Flow in Young, Healthy Males Following Acute Antioxidant Supplementation.

    Science.gov (United States)

    Kappus, Rebecca M; Bunsawat, Kanokwan; Rosenberg, Alexander J; Fernhall, Bo

    2017-03-01

    This study investigated the effects of acute antioxidant supplementation on endothelial function, exercise blood flow and oxidative stress biomarkers in 9 young African American compared to 10 Caucasian males (25.7±1.2 years). We hypothesized that African American males would have lower exercise blood flow and endothelial responsiveness compared to Caucasian males, and these responses would be improved following antioxidant supplementation. Ultrasonography was used to measure blood flow during handgrip exercise. Endothelial function was assessed using flow-mediated dilation, and lipid peroxidation was assessed by measuring levels of malondialdehyde-thiobarbituric acid reactive substances. African American males exhibited lower endothelial function than Caucasians at baseline (8.3±1.7 vs. 12.2±1.7%) and the difference was ameliorated with antioxidant supplementation (10.7±1.9% vs. 10.8±1.8%), but the interaction was not significant (p=0.10). There were no significant changes in malondialdehyde-thiobarbituric acid reactive substances following antioxidant supplementation. There was a significant increase in brachial blood flow and forearm vascular conductance with exercise but no differences with antioxidant supplementation. There were no group differences in exercise responses and no differences with antioxidant supplementation, suggesting a lack of influence of oxidative stress during exercise in this cohort. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Biflorin Ameliorates Memory Impairments Induced by Cholinergic Blockade in Mice

    Science.gov (United States)

    Jeon, Se Jin; Kim, Boseong; Ryu, Byeol; Kim, Eunji; Lee, Sunhee; Jang, Dae Sik; Ryu, Jong Hoon

    2017-01-01

    To examine the effect of biflorin, a component of Syzygium aromaticum, on memory deficit, we introduced a scopolamine-induced cognitive deficit mouse model. A single administration of biflorin increased latency time in the passive avoidance task, ameliorated alternation behavior in the Y-maze, and increased exploration time in the Morris water maze task, indicating the improvement of cognitive behaviors against cholinergic dysfunction. The biflorin-induced reverse of latency in the scopolamine-treated group was attenuated by MK-801, an NMDA receptor antagonist. Biflorin also enhanced cognitive function in a naïve mouse model. To understand the mechanism of biflorin for memory amelioration, we performed Western blot. Biflorin increased the activation of protein kinase C-ζ and its downstream signaling molecules in the hippocampus. These results suggest that biflorin ameliorates drug-induced memory impairment by modulation of protein kinase C-ζ signaling in mice, implying that biflorin could function as a possible therapeutic agent for the treatment of cognitive problems. PMID:27829270

  3. Biochar from commercially cultivated seaweed for soil amelioration

    Science.gov (United States)

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-01-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum – brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma – red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity. PMID:25856799

  4. Biochar from commercially cultivated seaweed for soil amelioration

    Science.gov (United States)

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-04-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum - brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma - red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity.

  5. Ghrelin Ameliorates Asthma by Inhibiting Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Fu, Tian; Wang, Lei; Zeng, Qingdi; Zhang, Yan; Sheng, Baowei; Han, Liping

    2017-12-01

    This study aimed to confirm the ameliorative effect of ghrelin on asthma and investigate its mechanism. The murine model of asthma was induced by ovalbumin (OVA) treatment and assessed by histological pathology and airway responsiveness to methacholine. The total and differential leukocytes were counted. Tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 levels in bronchoalveolar lavage fluid were quantified by commercial kits. The protein levels in pulmonary tissues were measured by Western blot analysis. Ghrelin ameliorated the histological pathology and airway hyperresponsiveness in the OVA-induced asthmatic mouse model. Consistently, OVA-increased total and differential leukocytes and levels of tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 in bronchoalveolar lavage fluid were significantly attenuated by ghrelin. Ghrelin prevented the increased protein levels of the endoplasmic reticulum stress markers glucose regulated protein 78 and CCAAT/enhancer binding protein homologous protein and reversed the reduced levels of p-Akt in asthmatic mice. Ghrelin might prevent endoplasmic reticulum stress activation by stimulating the Akt signaling pathway, which attenuated inflammation and ameliorated asthma in mice. Ghrelin might be a new target for asthma therapy. Copyright © 2017. Published by Elsevier Inc.

  6. Biochar from commercially cultivated seaweed for soil amelioration.

    Science.gov (United States)

    Roberts, David A; Paul, Nicholas A; Dworjanyn, Symon A; Bird, Michael I; de Nys, Rocky

    2015-04-09

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum--brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma--red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity.

  7. Lactucopicrin ameliorates oxidative stress mediated by scopolamine-induced neurotoxicity through activation of the NRF2 pathway.

    Science.gov (United States)

    Venkatesan, Ramu; Subedi, Lalita; Yeo, Eui-Ju; Kim, Sun Yeou

    2016-10-01

    Cholinergic activity plays a vital role in cognitive function, and is reduced in individuals with neurodegenerative diseases. Scopolamine, a muscarinic cholinergic antagonist, has been employed in many studies to understand, identify, and characterize therapeutic targets for Alzheimer's disease (AD). Scopolamine-induced dementia is associated with impairments in memory and cognitive function, as seen in patients with AD. The current study aimed to investigate the molecular mechanisms underlying scopolamine-induced cholinergic neuronal dysfunction and the neuroprotective effect of lactucopicrin, an inhibitor of acetylcholine esterase (AChE). We investigated apoptotic cell death, caspase activation, generation of reactive oxygen species (ROS), mitochondrial dysfunction, and the expression levels of anti- and pro-apoptotic proteins in scopolamine-treated C6 cells. We also analyzed the expression levels of antioxidant enzymes and nuclear factor (erythroid-derived 2)-like 2 (NRF2) in C6 cells and neurite outgrowth in N2a neuroblastoma cells. Our results revealed that 1 h scopolamine pre-treatment induced cytotoxicity by increasing apoptotic cell death via oxidative stress-mediated caspase 3 activation and mitochondrial dysfunction. Scopolamine also downregulated the expression the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase, and the transcription factor NRF2. Lactucopicrin treatment protected C6 cells from scopolamine-induced toxicity by reversing the effects of scopolamine on those markers of toxicity. In addition, scopolamine attenuated the secretion of neurotrophic nerve growth factor (NGF) in C6 cells and neurite outgrowth in N2a cells. As expected, lactucopicrin treatment enhanced NGF secretion and neurite outgrowth. Our study is the first to show that lactucopicrin, a potential neuroprotective agent, ameliorates scopolamine-induced cholinergic dysfunction via NRF2 activation and subsequent expression of antioxidant enzymes

  8. Icariin Ameliorate Thiram-Induced Tibial Dyschondroplasia via Regulation of WNT4 and VEGF Expression in Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Hui Zhang

    2018-02-01

    Full Text Available Tibial dyschondroplasia (TD is main bone problem in fast growing poultry birds that effect proximal growth plate (GP of tibia bone. TD is broadly defined as non-vascularized and non-mineralized, and enlarged GP with tibia bone deformation and lameness. Icariin (Epimedium sagittatum is a traditional Chinese medicine, which is commonly practiced in the treatment of various bone diseases. Recently, many researcher reports about the beneficial effects of icariin in relation to various types of bone conditions but no report is available about promoting effect of icariin against TD. Therefore, current study was conducted to explore the ameliorating effect of icariin in thiram-induced TD chickens. A total of 180 broiler chicks were equally distributed in three groups; control, TD induced by thiram (50 mg/kg, and icariin group (treated with icariin @10 mg/kg. All groups were administered with normal standard diet ad libitum regularly until the end of experiment. The wingless-type member 4 (WNT4 and vascular endothelial growth factor (VEGF genes and proteins expression were analyzed by quantitative real-time polymerase chain reaction and western blot analysis respectively. Tibial bone parameters, physiological changes in serum, antioxidant enzymes, and chicken growth performance were determined to assess advantage and protective effect of the medicine in broiler chicken. The expression of WNT4 was decreased while VEGF increased significantly (P < 0.05 in TD affected chicks. TD enhanced the GP, lameness, and irregular chondrocytes, while reduced the liver function, antioxidant enzymes in liver, and performance of chickens. Icariin treatment up-regulated WNT4 and down-regulated VEGF gene and protein expressions significantly (P < 0.05, restored the GP width, increased growth performance, corrected liver functions and antioxidant enzymes levels in liver, and mitigated the lameness in broiler chickens. In conclusion, icariin administration recovered GP size

  9. Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat.

    Science.gov (United States)

    Singh, Vishal; Jain, Manish; Misra, Ankita; Khanna, Vivek; Prakash, Prem; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

    2015-06-01

    Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism. High fructose feeding to rats and hamsters led to the development of insulin

  10. Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat

    Directory of Open Access Journals (Sweden)

    Vishal Singh

    2015-01-01

    Full Text Available Background & objectives: Curcuma oil (C. oil isolated from turmeric (Curcuma longa L. has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Methods: Male Golden Syrian hamsters on high fructose diet (HFr for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg or C. oil (300 mg/kg in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Results: Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c, peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1α and PGC-1β genes known to be involved in lipid and glucose metabolism. Interpretation

  11. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  12. Antioxidant degradation kinetics in apples.

    Science.gov (United States)

    Arora, Bindvi; Sethi, Shruti; Joshi, Alka; Sagar, V R; Sharma, R R

    2018-04-01

    The effect of shelf storage under ambient conditions of cut apple dices on degradation of bioactive compounds such ascorbic acid, total phenols, antioxidant activity (% DPPH inhibition) and PPO activity were investigated. The results indicated that antioxidant activity declined significantly over 80 min storage of diced apples at ambient temperature. Similar trend was observed for ascorbic acid, total phenols and PPO activity. Ascorbic acid, total phenols and antioxidant activity degradation followed first-order kinetics where the rate constant (k) was found to be in range for all the thirteen cultivars, though initial ascorbic acid and phenol content varied in different apple cultivars. The reaction rate constant (k) for first order degradation ranged from 1.16 to 1.97, 0.89 to 1.29 and 0.37 to 1.54 for antioxidant activity, total phenols and ascorbic acid, respectively. This explains that antioxidant activity degrades at higher rate than total phenols and ascorbic acid, which also corroborates that antioxidant activity is affected by both total phenols and ascorbic acid content. In general, total antioxidant activity for apple dices kept for 80 min under ambient conditions exhibited lower values as compared to control.

  13. Effect Of Using Black Cumin (Nigella Sativa) As Natural Antioxidant On Hyperlipidaemia And Antioxidant Activities In Senile Rats

    International Nuclear Information System (INIS)

    HAMZA, R.G.; MAHMOUD, K.A.

    2009-01-01

    The black cumin (Nigella sativa) is one of the important herbal plants that used widely in most of human diseases and food preservation. Chemical composition of irradiated black cumin (10 kGy); moisture, ash, crude protein, crude lipid, total carbohydrate and crude fiber, were evaluated. The GC for analysis of fatty acids showed that the number of identified fatty acids was 9; the important one was linoleic (natural antioxidant). GC/MS used for analysis of essential oil showed that the number of identified compounds was 16; the important ones were thymoquinone, eugenol and linalool (natural antioxidants). Also, this study was performed to examine the efficacy of the black cumin to ameliorate the induced hyperlipidemia in senile rats. Twenty eight male rats were equally and randomly categorized into four groups. High fat diet (20g fat / 100g diet) was daily administered to rats for 6 weeks. Other animals where fed daily on either raw or irradiated black cumin diet (1% w/w) for 6 weeks. The results revealed that high fat diet fed to rats significantly induced an increase in serum phospholipids, TG, TC, LDL-C, atherogenic index and lipid peroxides (MDA). Significant decrease was observed in HDL-C, blood antioxidant enzymes activity (superoxide dismutase and catalase) and concentration of reduced glutathione (GSH). The results obtained revealed that feeding rats on diet containing either raw or irradiated black cumin (1% w/w) induced significant improvement in the above mentioned parameters. There was non- significant difference between non-irradiated and irradiated black cumin. Moreover, supplementation of black cumin in diet of rats can offer protection against free radicals generated through oxidative stress as a consequence of hyperlipidemic food.

  14. Treatment of stable COPD: antioxidants

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    W. MacNee

    2005-09-01

    Full Text Available There is considerable evidence that an increased oxidative burden occurs in the lungs of patients with chronic obstructive pulmonary disease (COPD and this results in an imbalance between oxidants/antioxidants or oxidative stress, which may play a role in many of the processes involved in the pathogenesis of COPD. These include enhanced proteolytic activity, mucus hypersecretion and the enhanced inflammatory response in the lungs to inhaling tobacco smoke, which is characteristic of COPD. COPD is now recognised to have multiple systemic consequences, such as weight loss and skeletal muscle dysfunction. It is now thought that oxidative stress may extend beyond the lungs and is involved in these systemic effects. Antioxidant therapy therefore would seem to be a logical therapeutic approach in chronic obstructive pulmonary disease. There is a need for more potent antioxidant therapies to test the hypothesis that antioxidant drugs may be a new therapeutic strategy for the prevention and treatment of chronic obstructive pulmonary disease.

  15. Antioxidants Attenuate Oxidative Stress-Induced Hidden Blood Loss in Rats

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    Hong Qian

    2017-12-01

    Full Text Available Objective: Hidden blood loss (HBL, commonly seen after total knee or hip arthroplasty, causes postoperative anemia even after reinfusion or blood transfusion based on the visible blood loss volume. Recent studies demonstrated that oxidative stress might be involved in HBL. However, whether the antioxidants proanthocyanidin (PA or hydrogen water (HW can ameliorate HBL remains poorly understood. The aim of this study was to evaluate the effects of PA and HW on HBL. Materials and Methods: A rat HBL model was established through administration of linoleic acid with or without treatment with PA or HW. The levels of hemoglobin (Hb, red blood cell (RBC count, superoxide dismutase (SOD activity, glutathione peroxidase (GSH-PX activity, malondialdehyde (MDA, and ferryl Hb were measured. Results: RBC and Hb values as well as the activity of SOD and GSH-PX were reduced after administration of linoleic acid, which was ameliorated by treatment with PA or HW. In addition, the quantity of MDA was significantly decreased with the administration of PA or HW. Conclusion: PA and HW could ameliorate HBL in a rat model by reducing oxidative stress, suggesting that they might be used as a novel therapeutic approach in the prophylaxis or treatment of HBL in clinics.

  16. In Vitro Protective Effect and Antioxidant Mechanism of Resveratrol Induced by Dapsone Hydroxylamine in Human Cells.

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    Albuquerque, Rosyana V; Malcher, Nívea S; Amado, Lílian L; Coleman, Michael D; Dos Santos, Danielle C; Borges, Rosivaldo Sa; Valente, Sebastião Aldo S; Valente, Vera C; Monteiro, Marta Chagas

    2015-01-01

    Dapsone (DDS) hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV) on DDS hydroxylamine (DDS-NHOH) mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10-1000 μM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET), but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT) activity and reactive oxygen species (ROS) generation, but did not alter superoxide dismutase (SOD) activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy.

  17. The Healthy Effects of Strawberry Polyphenols: Which Strategy behind Antioxidant Capacity?

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    Forbes-Hernandez, Tamara Y; Gasparrini, Massimiliano; Afrin, Sadia; Bompadre, Stefano; Mezzetti, Bruno; Quiles, Josè L; Giampieri, Francesca; Battino, Maurizio

    2016-07-29

    Current evidence indicates that the consumption of strawberries, a natural source of a wide range of nutritive and bioactive compounds, is associated with the prevention and improvement of chronic-degenerative diseases. Studies involving cells and animals provide evidence on the anti-inflammatory, anticarcinogenic and antiproliferative activity of the strawberry. Epidemiological and clinical studies demonstrate that its acute consumption increases plasma antioxidant capacity, improves circulating inflammatory markers and ameliorates postprandial glycemic response. At the same time, a protracted intake reduces chronic inflammation and improves plasma lipid profile, supporting cardiovascular health, especially in individuals with increased risk for metabolic syndrome. To explain these beneficial effects, much attention has been paid in the past to the antioxidant properties of strawberry polyphenols. However, recent research has shown that their biological and functional activities are related not only to the antioxidant capacity but also to the modulation of many cellular pathways involved in metabolism, survival, proliferation, and antioxidant defenses. The aim of this review is to update and discuss the molecular and cellular mechanisms proposed in recent studies to elucidate the healthy effects of strawberry polyphenols against the most common chronic diseases, such as cancer, cardiovascular diseases, metabolic syndrome, and inflammation.

  18. In Vitro Protective Effect and Antioxidant Mechanism of Resveratrol Induced by Dapsone Hydroxylamine in Human Cells.

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    Rosyana V Albuquerque

    Full Text Available Dapsone (DDS hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV on DDS hydroxylamine (DDS-NHOH mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10-1000 μM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET, but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT activity and reactive oxygen species (ROS generation, but did not alter superoxide dismutase (SOD activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy.

  19. COPD: balancing oxidants and antioxidants

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    Fischer BM

    2015-02-01

    Full Text Available Bernard M Fischer,1,* Judith A Voynow,2,* Andrew J Ghio3,* 1Department of Pediatrics, Duke University Medical Center, Durham, NC, USA; 2Department of Pediatrics, Children's Hospital of Richmond at Virginia Commonwealth University, Richmond, VA, USA; 3National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Chapel Hill, NC, USA *These authors contributed equally to this work Abstract: Chronic obstructive pulmonary disease (COPD is one of the most common chronic illnesses in the world. The disease encompasses emphysema, chronic bronchitis, and small airway obstruction and can be caused by environmental exposures, primarily cigarette smoking. Since only a small subset of smokers develop COPD, it is believed that host factors interact with the environment to increase the propensity to develop disease. The major pathogenic factors causing disease include infection and inflammation, protease and antiprotease imbalance, and oxidative stress overwhelming antioxidant defenses. In this review, we will discuss the major environmental and host sources for oxidative stress; discuss how oxidative stress regulates chronic bronchitis; review the latest information on genetic predisposition to COPD, specifically focusing on oxidant/antioxidant imbalance; and review future antioxidant therapeutic options for COPD. The complexity of COPD will necessitate a multi-target therapeutic approach. It is likely that antioxidant supplementation and dietary antioxidants will have a place in these future combination therapies. Keywords: cigarette smoking, mucins, gene regulation, Chinese herbs, acupuncture, dietary antioxidants

  20. Cadmium exposure route affects antioxidant responses in the mayfly Centroptilum triangulifer

    International Nuclear Information System (INIS)

    Xie Lingtian; Buchwalter, David B.

    2011-01-01

    Highlights: ► In the mayfly Centroptilum triangulifer, antioxidant enzymes catalase and superoxide dismutase were suppressed by dietary cadmium (Cd) exposures, but not dissolved exposures. ► Dietary Cd reduced concentrations of active glutathione in whole insect homogenates. ► These findings suggest that diet derived Cd is potentially more toxic than aqueous derived Cd in this mayfly, and may help explain the disconnection between laboratory and field data for aquatic insect responses to trace metal pollution. - Abstract: Aquatic organisms accumulate metals directly from water and from their diets. Exposure to metals is known to generate oxidative stress in living organisms and this stress may be ameliorated via activation of antioxidant enzymes and non-enzymatic antioxidants. To determine if antioxidant physiology is dependent on Cd exposure route in the mayfly Centroptilum triangulifer, we exposed larvae to environmentally relevant concentrations of Cd from isolated dissolved or dietary exposure routes to achieve comparable tissue concentrations. Dissolved Cd had no effect on the antioxidant enzymes examined. However, dietary Cd significantly suppressed catalase and superoxide dismutase activities, and decreased concentrations of the reduced (active) form of glutathione in C. triangulifer larvae. These findings suggest that dietary Cd is potentially more toxic than aqueously derived Cd in this mayfly. We further examined the effect of dietary Cd tissue loading rates on antioxidant enzyme suppression and found that absolute tissue load appeared more important than loading rate. These results may help explain why insects are routinely unresponsive to dissolved metal exposures in the laboratory, yet highly responsive to metal pollution in nature.

  1. Bioactive compounds and antioxidant activity of Rosa canina L. biotypes from spontaneous flora of Transylvania.

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    Roman, Ioana; Stănilă, Andreea; Stănilă, Sorin

    2013-04-23

    The theoretical, but especially the practical values of identifying the biochemical compounds from the Rosa canina L. fruits are of present interest, this aspect being illustrated by the numerous researches. It was reported that the Rosa canina L. fruit, with its high ascorbic acid, phenolics and flavonoids contents, have antioxidant, antimutagenic and anticarcinogenic effects.This study was performed on order to evaluate the amount of the main phytochemicals (vitamin C, total polyphenols, and total flavonoids) content and their antioxidant activity. The results obtained revealed that the average amounts of vitamin C within the studied genotypes were: 360.22 mg/100 g frozen pulp (var. transitoria f. ramosissima, altitude 1250 m) and 112.20 mg/100 g frozen pulp (var. assiensis, altitude 440 m), giving a good correlation between the vitamin C content of the rosehip and the altitude. The total polyphenols content varied from 575 mg/100 g frozen pulp (var. transitoria f. ramosissima) to 326 mg/100 g frozen pulp (var. lutetiana f. fallens). The total flavonoids content showed the highest value for var. assiensis variant 163.3 mg/100 g frozen pulp and the lowest value attributed to var. transitoria f. montivaga 101.3 mg/100 g frozen pulp. The antioxidant activity of eight rose hip extracts from wild Transylvania populations was investigated through DPPH method. The antioxidant activity revealed a good correlation only with vitamin C content and total polyphenols. Eight Rose hip fruit species were compared taking into consideration the ascorbic acid, total polyphenols, total flavonoids contents and their antioxidant activity. Based on these results, two of the rosehip genotypes that were analysed could be of perspective for these species' amelioration, due to their content of phytochemicals mentioned above. These varieties are var. transitoria f. ramosissima (Bistrita-Nasaud, Agiesel) and var. transitoria f. montivaga (Bistrita-Nasaud, Salva) which can be used as a

  2. Terminalia pallida fruit ethanolic extract ameliorates lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase in isoproterenol-induced myocardial infarcted rats

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    Althaf Hussain Shaik

    2018-03-01

    Full Text Available The present study aimed to evaluate the effect of Terminalia pallida fruit ethanolic extract (TpFE on lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase (PON in isoproterenol (ISO-induced myocardial infarcted rats. PON is an excellent serum antioxidant enzyme which involves in the protection of low density lipoprotein cholesterol (LDL-C from the process of oxidation for the prevention of cardiovascular diseases. ISO caused a significant increase in the concentration of total cholesterol, triglycerides, LDL-C, very low density lipoprotein cholesterol and lipid peroxidation whereas significant decrease in the concentration of high density lipoprotein cholesterol. ISO administration also significantly decreased the activities of lecithin cholesterol acyl transferase, PON and lipoprotein lipase whereas significantly increased the activity of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Oral pretreatment of TpFE at doses 100, 300 and 500 mg/kg body weight (bw and gallic acid (15 mg/kg bw for 30 days challenged with concurrent injection of ISO (85 mg/kg bw on 29th and 30th day significantly attenuated these alterations and restored the levels of lipids, lipoproteins and the activities of lipid metabolizing enzymes. Also TpFE significantly elevated the serum antioxidant enzyme PON. This is the first report revealed that pretreatment with TPFE ameliorated lipid metabolic marker enzymes and increased the antioxidant PON in ISO treated male albino Wistar rats. Keywords: Terminalia pallida fruit, Gallic acid, Isoproterenol, Lipid metabolism marker enzymes, Paraoxonase, Myocardial infarction

  3. Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway

    International Nuclear Information System (INIS)

    Wu, Juan; Liu, Xinhui; Fan, Jinjin; Chen, Wenfang; Wang, Juan; Zeng, Youjia; Feng, Xiaorang; Yu, Xueqing; Yang, Xiao

    2014-01-01

    Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5 mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10 mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes

  4. Potential ameliorative effects of grape seed-derived polyphenols against cadmium induced prostatic deficits.

    Science.gov (United States)

    Lei, Yongfang; Chen, Qian; Chen, Jinglou; Liu, Dong

    2017-07-01

    Grape (Vitis vinifera) is consumed as fruit and wine for people. In this study, rat model of prostatic deficits was induced by orally receiving 60mg/L cadmium chlorine (CdCl 2 ) through drinking water for 20 weeks. Grape seed-derived polyphenols extract (GSP) was orally given for 20 weeks. Finally, the prostatic levels of E-cadherin, fibronectin, and α-smooth muscle actin were measured by immunohistochemical and qPCR analysis. The oxidative stress was measured by detecting the levels of malondialdehyde, nitric oxide, reduced glutathione/oxidized glutathione and enzymatic antioxidant status. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad3, phosphorylation-Smad3 (p-Smad3), Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured by western blot. The levels of microRNA (miR)-133a/b were measured by qPCR. It was observed that GSP ameliorated the prostatic oxidative stress and fibrosis induced by CdCl 2 . GSP also inhibited the over-generation of TGF-β1 and p-Smad3, as well as enhanced the levels of Smad7, Nrf-2, HO-1, γ-GCLC and miR-133a/b. These results showed that GSP could attenuate Cd-induced prostatic deficits. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Corticosterone synthesis inhibitor metyrapone ameliorates chronic hypobaric hypoxia induced memory impairment in rat.

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    Baitharu, Iswar; Deep, Satya Narayan; Jain, Vishal; Barhwal, Kalpana; Malhotra, Anand Swaroop; Hota, Sunil Kumar; Prasad, Dipti; Ilavazhagan, Govindasamy

    2012-03-01

    Chronic exposure to hypobaric hypoxia causes oxidative stress and neurodegeneration leading to memory impairment. The present study aimed at investigating the role of corticosterone in hypoxia induced neurodegeneration and effect of metyrapone, a corticosterone synthesis inhibitor that reduces the stress induced elevation of corticosterone without affecting the basal level, in ameliorating chronic hypobaric hypoxia induced cognitive decline. Rats were exposed to simulated altitude of 25,000 ft for 0, 3, 7, 14 and 21 days to determine the temporal alterations in corticosterone and its receptors following exposure to hypobaric hypoxia. Our results showed an elevation of corticosterone in plasma and hippocampal tissue following 7 days of exposure, which declined on prolonged hypoxic exposure for 21 days. A concomitant increase in ROS and lipid peroxidation was observed along with depletion of intracellular antioxidants. Glucocorticoid and mineralocorticoid receptors were upregulated on 3 and 7 days of hypoxic exposure. Though expression of Glut1 and Glut3 were upregulated on 3 days of hypoxic exposure, sharp decline in Glut1 expression following 7 days of hypoxic exposure leads to reduced neuronal glucose uptake. Administration of metyrapone from 3rd to 7th day of hypoxic exposure to suppress hypoxia induced increase in corticosterone levels resulted in reduced oxidative damage, neurodegeneration and improvement of intracellular energy status. The metyrapone treated hypoxic animals performed better in the Morris Water Maze. Further, administration of exogenous corticosterone along with metyrapone during hypoxic exposure blunted the neuroprotective effect of metyrapone indicating a role for corticosterone in mediating hypobaric hypoxia induced neurodegeneration and memory impairment. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Alpha-tocopherol ameliorates experimental autoimmune encephalomyelitis through the regulation of Th1 cells

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    Haikuo Xue

    2016-05-01

    Full Text Available Objective(s: Multiple sclerosis (MS is a serious neurological autoimmune disease, it commonly affects young adults. Vitamin E (Vit E is an important component of human diet with antioxidant activity, which protects the body’s biological systems. In order to assess the effect of Vit E treatment on this autoimmune disease, we established experimental autoimmune encephalomyelitis (EAE, the animal model of MS, and treated EAE with α-tocopherol (AT which is the main content of Vit E. Materials and Methods:Twenty C57BL/6 adult female mice were used and divided into two groups randomly. EAE was induced with myelin oligodendrocyte glycoprotein (MOG, and one group was treated with AT, at a dose of 100 mg/kg on the 3th day post-immunization with MOG, the other group was treated with 1% alcohol. Mice were euthanized on day 14, post-immunization, spleens were removed for assessing splenocytes proliferation and cytokine profile, and spinal cords were dissected to assess the infiltration of inflammatory cells in spinal cord. Results:AT was able to attenuate the severity of EAE and delay the disease progression. H&E staining and fast blue staining indicated that AT reduced the inflammation and the demyelination reaction in the spinal cord. Treatment with AT significantly decreased the proliferation of splenocytes. AT also inhibited the production of IFN-γ (Th1 cytokine, though the other cytokines were only affected slightly. Conclusion:According to the results, AT ameliorated EAE, through suppressing the proliferation of T cells and the Th1 response. AT may be used as a potential treatment for MS.

  7. Tinospora crispa Ameliorates Insulin Resistance Induced by High Fat Diet in Wistar Rats

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    Mohd Nazri Abu

    2015-01-01

    Full Text Available The antidiabetic properties of Tinospora crispa, a local herb that has been used in traditional Malay medicine and rich in antioxidant, were explored based on obesity-linked insulin resistance condition. Male Wistar rats were randomly divided into four groups, namely, the normal control (NC which received standard rodent diet, the high fat diet (HFD which received high fat diet only, the high fat diet treated with T. crispa (HFDTC, and the high fat diet treated with orlistat (HFDO. After sixteen weeks of treatment, blood and organs were harvested for analyses. Results showed that T. crispa significantly (p < 0.05 reduced the body weight (41.14 ± 1.40%, adiposity index serum levels (4.910 ± 0.80%, aspartate aminotransferase (AST: 161 ± 4.71 U/L, alanine aminotransferase (ALT: 100.95 ± 3.10 U/L, total cholesterol (TC: 18.55 ± 0.26 mmol/L, triglycerides (TG: 3.70 ± 0.11 mmol/L, blood glucose (8.50 ± 0.30 mmo/L, resistin (0.74 ± 0.20 ng/mL, and leptin (17.428 ± 1.50 ng/mL hormones in HFDTC group. The insulin (1.65 ± 0.07 pg/mL and C-peptide (136.48 pmol/L hormones were slightly decreased but within normal range. The histological results showed unharmed and intact liver tissues in HFDTC group. As a conclusion, T. crispa ameliorates insulin resistance-associated with obesity in Wistar rats fed with high fat diet.

  8. Chromium, selenium, and zinc multimineral enriched yeast supplementation ameliorates diabetes symptom in streptozocin-induced mice.

    Science.gov (United States)

    Liu, Jun; Bao, Wei; Jiang, Man; Zhang, Yan; Zhang, Xiping; Liu, Liegang

    2012-05-01

    Chromium, selenium, and zinc malnutrition has been implicated in the pathogenesis of diabetic mellitus. This study aims to investigate the effects of novel multiminerals-enriched yeast (MMEY) which are minerals supplementation containing elevated levels of chromium, selenium, and zinc simultaneously in a diabetic animal model. Streptozocin-induced diabetic male Balb/c mice (n = 80) were randomly divided into diabetes control group and three treatment groups. They were administrated oral gavages with low, medium, or high doses of MMEY, respectively. Meanwhile, healthy male Balb/c mice (n = 40) of the same body weight were randomly assigned into normal control group and high dose of MMEY control group. After 8 weeks duration of treatment, the animals were sacrificed by cervical dislocation. Serum glucose concentrations, lipid profiles, oxidative/antioxidant, and immunity status were determined. No significant adverse effects were observed in the high-dose MMEY control group. Treatment of the diabetic mice with medium- or high-dose MMEY significantly decreased serum glucose, triglyceride, total cholesterol, and malondialdehyde and increased high-density lipoprotein cholesterol, glutathione, and the activities of superoxide dismutase and glutathione peroxidase. In addition, MMEY ameliorated the pathological damage of the pancreatic islets, elevated the thymus or spleen coefficient, and increased the expressions of interleukin-2 and -4 in spleen lymphocytes compared with unsupplemented diabetic mice. In conclusion, these results indicate that supplemental MMEY inhibits hyperglycemia, abates oxidative stress, modulates disorders of lipid metabolism, and reduces the impairment of immune function in diabetic mice; especially notable are the protective effects of medium doses of MMEY on the islet cells of diabetic mice.

  9. Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts.

    Science.gov (United States)

    Waly, Mostafa I; Al-Rawahi, Amani S; Al Riyami, Marwa; Al-Kindi, Mohamed A; Al-Issaei, Halima K; Farooq, Sardar A; Al-Alawi, Ahmed; Rahman, Mohammad S

    2014-02-18

    Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Eighty Sprague-Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities.

  10. Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes.

    Science.gov (United States)

    de Peralta, Mauro S Porcel; Mouguelar, Valeria S; Sdrigotti, María Antonella; Ishiy, Felipe A A; Fanganiello, Roberto D; Passos-Bueno, Maria R; Coux, Gabriela; Calcaterra, Nora B

    2016-10-06

    Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1 +/- mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region. An increase of ROS along with the overexpression of redox-responsive genes was detected; furthermore, treatment with antioxidants ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae. On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp, a protein required for proper craniofacial development. Tcof1 knockdown in transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial cartilage development, reinforcing the notion that Cnbp has a role in the pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose-dependent manner by a ROS-cytoprotective action that prevented the redox-responsive genes' upregulation but did not normalize the synthesis of rRNAs. Finally, a positive correlation between the expression of CNBP and TCOF1 in mesenchymal cells from both control and TCS subjects was found. Based on this, we suggest CNBP as an additional target for new alternative therapeutic treatments to reduce craniofacial defects not only in TCS but also in other neurocristopathies.

  11. Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats

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    Tugba Yilmaz-Ozden

    2014-05-01

    Full Text Available Between their broad spectrum of action, vanadium compounds are shown to have insulin mimetic/enhancing effects. Increasing evidence in experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes and on the onset of diabetic complications. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the stomach tissue of diabetic rats. Male Swiss albino rats were randomly divided into 4 groups: control; control+vanadyl sulfate; diabetic; diabetic+vanadyl sulfate. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight. Vanadyl sulfate (100 mg/kg body weight was given daily by gavage for 60 days. At the last day of the experiment, stomach tissues were taken and homogenized to make a 10% (w/v homogenate. Catalase (CAT, superoxide dismutase (SOD, glutathione reductase (GR, glutathione peroxidase (GPx, glutathione-S-transferase (GST, myeloperoxidase (MPO, carbonic anhydrase (CA, glucose-6-phosphate dehydrogenase (G6PD and lactate dehydrogenase (LDH activities were determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH activities were increased in diabetic rats when compared to normal rats. Vanadium treatment significantly reduced the elevated activities of GR, GPx, GST compared with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH activities were insignificant. No significant change was seen for MPO activity between the groups. It was concluded that vanadium could be used for its ameliorative effect against oxidative stress in diabetes.

  12. Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats.

    Science.gov (United States)

    Yilmaz-Ozden, Tugba; Kurt-Sirin, Ozlem; Tunali, Sevim; Akev, Nuriye; Can, Ayse; Yanardag, Refiye

    2014-05-01

    Between their broad spectrum of action, vanadium compounds are shown to have insulin mimetic/enhancing effects. Increasing evidence in experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes and on the onset of diabetic complications. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the stomach tissue of diabetic rats. Male Swiss albino rats were randomly divided into 4 groups: control; control+vanadyl sulfate; diabetic; diabetic+vanadyl sulfate. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight). Vanadyl sulfate (100 mg/kg body weight) was given daily by gavage for 60 days. At the last day of the experiment, stomach tissues were taken and homogenized to make a 10% (w/v) homogenate. Catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), myeloperoxidase (MPO), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) activities were determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH activities were increased in diabetic rats when compared to normal rats. Vanadium treatment significantly reduced the elevated activities of GR, GPx, GST compared with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH activities were insignificant. No significant change was seen for MPO activity between the groups. It was concluded that vanadium could be used for its ameliorative effect against oxidative stress in diabetes.

  13. Unfolding the mechanism of cisplatin induced pathophysiology in spleen and its amelioration by carnosine.

    Science.gov (United States)

    Banerjee, Sharmistha; Sinha, Krishnendu; Chowdhury, Sayantani; Sil, Parames C

    2018-01-05

    cis-Diamminedichloroplatinum (cisplatin) is an effective chemotherapeutic and is widely used for the treatment of various types of solid tumors. Bio-distribution of cisplatin to other organs due to poor targeting towards only cancer cells constitutes the backbone of cisplatin-induced toxicity. The adverse effect of this drug on spleen is not well characterized so far. Therefore, we have set our goal to explore the mechanism of the cisplatin-induced pathophysiology of the spleen and would also like to evaluate whether carnosine, an endogenous neurotransmitter and antioxidant, can ameliorate this pathophysiological response. We found a dose and time-dependent increase of the pro-inflammatory cytokine, TNF-α, in the spleen tissue of the experimental mice exposed to 10 and 20 mg/kg body weight of cisplatin. The increase in inflammatory cytokine can be attributed to the activation of the transcription factor, NF-ĸB. This also aids in the transcription of other pro-inflammatory cytokines and cellular adhesion molecules. Exposure of animals to cisplatin at both the doses resulted in ROS and NO production leading to oxidative stress. The MAP Kinase pathway, especially JNK activation, was also triggered by cisplatin. Eventually, the persistence of inflammatory response and oxidative stress lead to apoptosis through extrinsic pathway. Carnosine has been found to restore the expression of inflammatory molecules and catalase to normal levels through inhibition of pro-inflammatory cytokines, oxidative stress, NF-ĸB and JNK. Carnosine also protected the splenic cells from apoptosis. Our study elucidated the detailed mechanism of cisplatin-induced spleen toxicity and use of carnosine as a protective agent against this cytotoxic response. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. N-acetylcysteine (NAC) ameliorates Epstein-Barr virus latent membrane protein 1 induced chronic inflammation.

    Science.gov (United States)

    Gao, Xiao; Lampraki, Eirini-Maria; Al-Khalidi, Sarwah; Qureshi, Muhammad Asif; Desai, Rhea; Wilson, Joanna Beatrice

    2017-01-01

    Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions. LMP1 signalling leads to persistent deregulated expression of multiple proteins throughout the mouse life span, including TGFα S100A9 and chitinase-like proteins. Additionally, as the inflammation increases, numerous chemokines and cytokines are produced which promulgate the inflammation. Deposition of IgM, IgG, IgA and IgE and complement activation form part of this process and through genetic deletion of CD40, we show that this contributes to the more tissue-destructive aspects of the phenotype. Treatment of the mice with N-acetylcysteine (NAC), an antioxidant which feeds into the body's natural redox regulatory system through glutathione synthesis, resulted in a significantly reduced leukocyte infiltrate in the inflamed tissue, amelioration of the pathological features and delay in the inflammatory signature measured by in vivo imaging. Reducing the degree of inflammation achieved through NAC treatment, had the knock on effect of reducing leukocyte recruitment to the inflamed site, thereby slowing the progression of the pathology. These data support the idea that NAC could be considered as a treatment to alleviate chronic inflammatory pathologies, including post-viral disease. Additionally, the model described can be used to effectively monitor and accurately measure

  15. Hydrogen-rich saline ameliorates the severity of L-arginine-induced acute pancreatitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Han; Sun, Yan Ping; Li, Yang [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Liu, Wen Wu [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Xiang, Hong Gang [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Fan, Lie Ying [Department of Clinical Laboratory, Shanghai East Hospital, Tong Ji University, Shanghai 200120 (China); Sun, Qiang [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Xu, Xin Yun [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Cai, Jian Mei [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Ruan, Can Ping; Su, Ning; Yan, Rong Lin [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Sun, Xue Jun, E-mail: sunxjk@hotmail.com [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Wang, Qiang, E-mail: wang2929@hotmail.com [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China)

    2010-03-05

    Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the L-arginine (L-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of L-Arg, each at concentrations of 250 mg/100 g body weight, with an interval of 1 h. Hydrogen-rich saline (>0.6 mM, 6 ml/kg) or saline (6 ml/kg) was administered, respectively, via tail vein 15 min after each L-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreas were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-{kappa}B) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of L-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-{kappa}B activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-{kappa}B activation and to promote acinar cell proliferation.

  16. Aronia Berry Extract Ameliorates the Severity of Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

    Science.gov (United States)

    Kang, Sa-Haeng; Jeon, Yong-Deok; Moon, Kwang-Hyun; Lee, Jeong-Ho; Kim, Dae-Geun; Kim, Wook; Myung, Hyun; Kim, Jong-Sung; Kim, Hyun-Ju; Bang, Keuk-Soo; Jin, Jong-Sik

    2017-07-01

    Inflammatory bowel disease, including Crohn's disease and ulcerative colitis (UC), is a group of inflammatory conditions of the colon and small intestine. UC is a chronic inflammatory disorder of the colon and rectum that includes intervals of acute exacerbation. Although recent studies have suggested that proinflammatory cytokines might have initiated the inflammatory responses in UC, its etiology remains unclear. Aronia berries are rich in dietary polyphenols such as phenolic acids, anthocyanins, flavonoids, and proanthocyanidins with various health benefits, including antioxidant, anti-inflammatory, and antiaging activities. The objective of this study was to determine whether Aronia berry can be an effective intervention for the treatment of UC. BALB/c mice were administered 5% dextran sulfate sodium (DSS) to induce UC. They were then given Aronia berry extracts at concentrations of 10 or 100 mg/kg. During the induction of UC, the expression levels of nuclear factor-kappa B were increased in colonic epithelial cells and immune cells, leading to increased proinflammatory cytokine levels. Aronia berry extract significantly improved the clinical signs of DSS-induced UC, including body weight loss, colon length shortening, and disease activity index increase, with histological markers of colon injury. Furthermore, oral administration of Aronia berry extract inhibited prostaglandin E 2 production in DSS-induced colitis and decreased the levels of nitric oxide, interleukin-6, and tumor necrosis factor-α in lipopolysaccharide-stimulated macrophages. These results suggest that Aronia berry extract could efficiently ameliorate clinical signs and inflammatory mediators of UC. Therefore, Aronia berry might be a promising natural treatment for UC.

  17. Antioxidants stabilizing fish oils : effect of antioxidant, storage temperature and type of fish oil

    OpenAIRE

    Kasbo, Mari Kristine

    2012-01-01

    The aim of this study was to investigate four commercially available antioxidants in two fish oils. The antioxidants were investigated to see which one of them is most efficient in preventing oxidation. Antioxidants were added in three levels to find the optimal concentration. In addition a possible synergistic effect between the antioxidants was investigated. Two different oils with different concentration of EPA and DHA were added antioxidants. Four of the antioxidants were single antioxida...

  18. Ameliorative role of nano-ceria against amine coated Ag-NP induced toxicity in Labeo rohita

    Science.gov (United States)

    Khan, Muhammad Saleem; Qureshi, Naureen Aziz; Jabeen, Farhat

    2018-03-01

    Silver nanoparticles (Ag-NPs) and its byproducts can spread pollution in aquatic habitat. Liver and gills are key target for toxicity. Oxidative stress, tissue alterations, and hemotoxicity are assumed to be associated with Ag-NPs in target animals. Cerium oxide nanoparticles (nano-ceria) show antioxidant potential in scavenging the free radicals generated in Ag-NP-induced oxidative stress. We determined ameliorated role of nano-ceria against Ag-NP-induced toxicity in fresh water Labeo rohita (L. rohita). Four groups were used in study including control, nano-ceria, Ag-NPs, and Ag-NPs + nano-ceria. Ag-NPs (30 mg l-1) and nano-ceria (50 µg kg-1) were given through water and prepared feed, respectively. The samples were taken after 28 days. Results demonstrated that pre-treatment of nano-ceria recovered L. rohita from Ag-NP-induced toxicity and oxidative stress. Nano-ceria pre-treatment actively mimics the activity of GST, GSH, CAT, and SOD. Furthermore, Ag-NPs' treatment caused severe inflammation and necrosis in hepatic parenchyma which leaded to congestion of blood in hepatic tissues. Accumulation of a yellow pigment in hepatic tissue was also seen due to necrosis of affected cells. In nano-ceria pre-treatment, there was no congestion in hepatic tissue. Vacuolization of cells and necrosis in some area was recorded in nano-ceria pre-treated group, but the gill and hepatic tissue showed improvement against Ag-NP-induced damage. Nano-ceria pre-treatment also improved hematological parameters in Ag-NP-treated fish. This study concluded that Ag-NP-induced toxicity in treated fish and pre-treatment of nano-ceria show ameliorative role.

  19. Oligo-Porphyran Ameliorates Neurobehavioral Deficits in Parkinsonian Mice by Regulating the PI3K/Akt/Bcl-2 Pathway

    Directory of Open Access Journals (Sweden)

    Yingjuan Liu

    2018-03-01

    Full Text Available Parkinson’s disease (PD is a neurodegenerative movement disorder that is caused by a selective loss of dopaminergic neurons. Current PD treatments provide symptomatic relief but do not prevent or decelerate disease progression. Previous studies have suggested that acetylated and phosphorylated porphyran, derived from Porphyra, produces a neuroprotective effect against 6-OHDA-induced damage. Due to its antioxidant and neuroprotective potential, this study evaluates whether oligo-porphyran (OP could be beneficial in an experimental model of PD in mice. The drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP was intraperitoneally injected (20 mg/kg body weight for seven days to simulate PD, followed by OP administration. We found that the behavioral deficits in spontaneous motor activity, latency to descend in a pole test, and suspension in a traction test were ameliorated, and excessive dopamine (DA metabolism was suppressed after OP treatment. Additionally, we found that OP protected dopaminergic neurons by preventing MPTP-induced decreases in dopaminergic transporter and tyrosine hydroxylase protein levels. We speculated whether OP regulates a signaling pathway that affects the behavioral changes seen in PD mice. In this study, the PI3K/Akt/Bcl-2 pathway was detected. Our results demonstrate that OP increased the phosphorylation of PI3K/Akt/GSK-3β and inhibited the activation of caspase-3 and poly (ADP-ribose polymerase, with changes in the Bax/Bcl-2 ratio. These results showed that OP might promote DA neuron survival in vivo by regulating the PI3K/Akt/Bcl-2 pathway, thereby ameliorating the neurobehavioral deficits in a PD mouse model and suggesting OP as a neuroprotective treatment for PD.

  20. Quercetin ameliorates oxidative stress, inflammation and apoptosis in the heart of streptozotocin-nicotinamide-induced adult male diabetic rats.

    Science.gov (United States)

    Roslan, Josef; Giribabu, Nelli; Karim, Kamarulzaman; Salleh, Naguib

    2017-02-01

    Quercetin is known to possess beneficial effects in ameliorating diabetic complications, however the mechanisms underlying cardioprotective effect of this compound in diabetes is not fully revealed. In this study, quercetin effect on oxidative stress, inflammation and apoptosis in the heart in diabetes were investigated. Normal and streptozotocin-nicotinamide induced adult male diabetic rats received quercetin (10, 25 and 50mg/kg/bw) orally for 28days were anesthetized and hemodynamic parameters i.e. systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured. Blood was collected for analyses of fasting glucose (FBG), insulin and cardiac injury marker levels (troponin-C, CK-MB and LDH). Following sacrificed, heart was harvested and histopathological changes were observed. Heart was subjected for analyses of oxidative stress marker i.e. lipid peroxidation and activity and expression levels of anti-oxidative enzymes i.e. SOD, CAT and GPx. Levels of inflammation in the heart were determined by measuring nuclear factor (p65-NF-κB), tumor necrosis factor (TNF-α), interleukins (IL)-1β and IL-6 levels by using enzyme-linked immunoassay (ELISA). Distribution and expression levels of TNF-α and Ikk-β (inflammatory markers), caspase-3, caspase-9, Blc-2 and Bax (apoptosis markers) in the heart were identified by immunohistochemistry and Western blotting respectively. Administration of quercetin to diabetic rats caused significant decrease in FBG and cardiac injury marker levels with increased in insulin levels. In diabetic rat heart, lesser histopathological changes were observed with oxidative stress, inflammation and apoptosis levels markedly decreased. Quercetin could potentially be used to ameliorate myocardial damage due to oxidative stress, inflammation and apoptosis in diabetes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Neuroprotective effects of Caralluma tuberculata on ameliorating cognitive impairment in a d-galactose-induced mouse model.

    Science.gov (United States)

    Khan, Muhammad Zahid; Atlas, Nagina; Nawaz, Waqas

    2016-12-01

    Cognitive deficiency and oxidative stress have been well documented in aging disorders including Alzheimer's disease. The aim of this study was to investigate the therapeutic efficacy of Caralluma tuberculata methanolic extract (CTME) on cognitive impairment in mice induced with d-galactose. In this study we assessed the therapeutic efficacy of CTME on cognitive impairment in mice induced with d-galactose by conduction of behavioral and cognitive performance tests. In order to explore the possible role of CTME against d-galactose-induced oxidative damages, various biochemical indicators were assessed. Chronic administration of d-galactose (150mg/kgd, s.c.) for 7 weeks significantly impaired cognitive performance (in step-through passive, active avoidance test, Hole-Board test, Novel object recognition task and Morris water maze) and oxidative defense as compared to the control group. The results revealed that CTME treatment for two weeks (100, 200 and 300mg/kg p.o) significantly ameliorated cognitive performance and oxidative defense. All groups of CTME enhanced the learning and memory ability in step-through passive, active avoidance test, Hole-Board test Novel object recognition task and Morris water maze. Furthermore, high and middle level of CTME (300 and 200mg/kg p.o) significantly increased Total antioxidative capacity (T-AOC), Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity, neprilysin (NEP), and β-site AβPP cleaving enzyme 1 (BACE1) expression while Nitric Oxide (NO), Nitric Oxide Synthase (NOS) activity and Malondialdehyde (MDA) concentration, and the level of Aβ1-42 and presenilin 1 (PS1) were decreased. The present study showed that CTME have a significant relieving effect on learning, memory and spontaneous activities in d-galactose-induced mice model, and ameliorates cognitive impairment and biochemical dysfunction in mice. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Amelioration of excision wounds by topical application of green synthesized, formulated silver and gold nanoparticles in albino Wistar rats.

    Science.gov (United States)

    Naraginti, Saraschandra; Kumari, P Lakshmi; Das, Raunak Kumar; Sivakumar, A; Patil, Sagar Hindurao; Andhalkar, Vaibhav Vilas

    2016-05-01

    Wound healing, a complex biological process, has attained a lot of attention as dermatologists are primarily interested in stimulated wound closure without formation of scar or a faint scar. The recent upsurgence of nanotechnology has provided novel therapeutic materials in the form of silver and gold nanoparticles which accelerate the wound healing process. The effect of formulated nanoparticles using Coleus forskohlii root extract (green synthesized) has been tried out for ameliorating full thickness excision wounds in albino Wistar male rats. The evaluation of in vivo activity of nanoparticles in wound healing was carried out on open wounds made by excision on the dorsal sides of albino Wistar rats under anesthesia, and the healing of the wounds was assessed. Histological aspects of the healing process were studied by a HE (Hematoxylin and Eosin) staining method to assess various degrees of re-epithelialization and the linear alignment of the granulation tissue whereas Van Gieson's histochemical staining was performed to observe collagen fibers. The healing action shown by the formulated nanoparticles was remarkable during the early stages of wound healing, which resulted in the substantial reduction of the whole healing period. Topical application of formulated gold nanoparticles was found to be more effective in suppressing inflammation and stimulating re-epithelialization compared to silver nanoparticles during the healing process. The results throw light on the amelioration of excision wounds using nanoparticles which could be a novel therapeutic way of improving wound healing in clinical practice. The mechanism of advanced healing action of both types of nanoparticles could be due to their antimicrobial, antioxidant and anti-inflammatory properties. Copyright © 2016. Published by Elsevier B.V.

  3. Swimming, but not vitamin E, ameliorates prothrombotic state and hypofibrinolysis in a rat model of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Sakr, Hussein F; Abbas, Amr M; Haidara, Mohamed A

    2018-01-26

    Nonalcoholic fatty liver disease (NAFLD) is associated with a systemic procoagulant hypofibrinolysis state that is considered as a risk factor for microangiopathy and peripheral vascular diseases. Swimming exercise ameliorates the metabolic dysfunction in type 2 diabetes. Vitamin E is a natural antioxidant that reduces the risk of endothelial dysfunction in metabolic syndrome. The aim of the present study is to investigate the effect of combined swimming exercise with vitamin E on coagulation as well as blood fibrinolysis markers in rats with NAFLD. Eighty male rats were divided into control, control+vitamin E, control+exercise, high-fat diet (HFD), HFD+vitamin E, HFD+exercise, and HFD+vitamin E+exercise groups. Glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), alanine transaminase (ALT) and aspartate transaminase (AST), intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelin-1, von Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor (PAI-1), fibrin degradation products (FDP), platelet count and aggregation, bleeding and clotting times, activated partial thromboplastin time (aPTT), and prothrombin time (PT) were determined. HFD increased lipid profile, insulin, glucose, HOMA-IR, liver enzymes, adhesion molecules, endothelin-1, vWF, platelet aggregation, fibrinogen, FDP, and PAI-1, and decreased clotting and bleeding times and HDL. Although exercise reduced lipid profile, glucose, insulin, HOMA-IR, vWF, platelet aggregation, fibrinogen, FDP, and PAI-1 and increased PT, aPTT, bleeding and clotting times, and HDL, vitamin E had no effect. Exercise, but not vitamin E, ameliorated the HFD-induced prothrombotic state and enhanced fibrinolytic activity.

  4. A note on inventory model for ameliorating items with time dependent second order demand rate

    Directory of Open Access Journals (Sweden)

    Gobinda Chandra Panda

    2013-03-01

    Full Text Available Background: This paper is concerned with the development of ameliorating inventory models. The ameliorating inventory is the inventory of goods whose utility increases over the time by ameliorating activation. Material and Methods: This study is performed according to two areas: one is an economic order quantity (EOQ model for the items whose utility is ameliorating in accordance with Weibull distribution, and the other is a partial selling quantity (PSQ model developed for selling the surplus inventory accumulated by ameliorating activation with linear demand. The aim of this paper was to develop a mathematical model for inventory type concerned in the paper. Numerical examples were presented show the effect of ameliorating rate on inventory polices.  Results and Conclusions:  The inventory model for items with Weibull ameliorating is developed. For the case of small ameliorating rate (less than linear demand rate, EOQ model is developed, and for the case where ameliorating rate is greater than linear demand rate, PSQ model is developed.  .  

  5. Contribution of Macromolecular Antioxidants to Dietary Antioxidant Capacity: A Study in the Spanish Mediterranean Diet.

    Science.gov (United States)

    Pérez-Jiménez, Jara; Díaz-Rubio, M Elena; Saura-Calixto, Fulgencio

    2015-12-01

    Epidemiological and clinical studies show that diets with a high antioxidant capacity, such us those rich in plant food and beverages, are associated with significant decreases in the overall risk of cardiovascular disease or colorectal cancer. Current studies on dietary antioxidants and dietary antioxidant capacity focus exclusively on low molecular weight or soluble antioxidants (vitamins C and E, phenolic compounds and carotenoids), ignoring macromolecular antioxidants. These are polymeric phenolic compounds or polyphenols and carotenoids linked to plant food macromolecules that yield bioavailable metabolites by the action of the microbiota with significant effects either local and/or systemic after absorption. This study determined the antioxidant capacity of the Spanish Mediterranean diet including for the first time both soluble and macromolecular antioxidants. Antioxidant capacity and consumption data of the 54 most consumed plant foods and beverages were used. Results showed that macromolecular antioxidants are the major dietary antioxidants, contributing a 61% to the diet antioxidant capacity (8000 μmol Trolox, determined by ABTS method). The antioxidant capacity data for foods and beverages provided here may be used to estimate the dietary antioxidant capacity in different populations, where similar contributions of macromolecular antioxidants may be expected, and also to design antioxidant-rich diets. Including macromolecular antioxidants in mechanistic, intervention and observational studies on dietary antioxidants may contribute to a better understanding of the role of antioxidants in nutrition and health.

  6. Aqueous root extract of Dicoma anomala Sond ameliorates ...

    African Journals Online (AJOL)

    free radicals and stimulates lipid peroxidation which perhaps cause irreversible damage to the myocardial membrane [6]. Thus, a high production of reactive oxygen species (ROS) may be a unifying mechanism in ischemic injury progression and antioxidants administration may protect against ISP induced cardiac damage.

  7. Ameliorative effect of protein and calcium on fluoride-induced ...

    African Journals Online (AJOL)

    In liver, low superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, high malondialdehyde (MDA) content, and evident mitochondria lesions in HiF group indicated a significant oxidative stress, while Pr or Ca supplementation brought an ultrastructural repair and a recovery antioxidant defense in liver.

  8. Cytotoxicity of chlopyrifos and cypermethrin: The ameliorative effects ...

    African Journals Online (AJOL)

    It explains the mechanism of action of chlopyrifos and cypermethrin and the role of oxidative stress. It sheds light on the interaction between chlopyrifos and cypermethrin as observed in many cocktails of pesticide combinations today. It also explains the adverse health effects of pesticides and some antioxidants which may ...

  9. Curcumin ameliorates gastrointestinal dysfunction and oxidative damage in diabetic rats

    Directory of Open Access Journals (Sweden)

    Nitin Indarchandji Kochar

    2014-05-01

    Full Text Available Diabetes is known to be associated with gastrointestinal complications characterized by nausea, vomiting, early satiety, bloating, and abdominal discomfort or pain commonly occurring in the advanced stages of the disease. Curcumin is the lipid-soluble antioxidant obtained from the rhizomes of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and oxidative stress pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, literature lacks conclusive evidence supporting its use as a therapeutic agent for the treatment of diabetes induced gastrointestinal complications. Hence, Curcumin was given in different doses to SD rats after 4 weeks of diabetic GI complication induction. At the end of 4 weeks, significant GI dysfunction characterized by weight loss, delayed gastric emptying and intestinal transit associated with reduction in antioxidant enzyme levels and increased lipid peroxidation was observed.  Upon treatment with Curcumin for further 4 weeks, reversal of GI dysfunction evidenced by restoration of body weight, GI emptying, intestinal transit, and restoration of antioxidant enzyme level and lipid peroxidation proves the beneficial role of Curcumin in diabetes induced GI complications due to its antioxidant potential.     

  10. Ethanol stem bark extract of Rauwolfia vomitoria ameliorates MPTP ...

    African Journals Online (AJOL)

    Methods: The Parkinson's disease was induced in rats by a single intraperitoneal (IP) injection of MPTP. After 72h of induction, the young adult male rats were treated with oral administration of stem bark ethanol extract of the plant daily for 2 weeks. The blood chemistry, antioxidant markers and brain dopamine levels were ...

  11. Monosodium glutamate toxicity: Sida acuta leaf extract ameliorated ...

    African Journals Online (AJOL)

    The brain is reportedly sensitive to monosodium glutamate (MSG) toxicity via oxidative stress. Sida acuta leaf ethanolic extract (SALEE) possesses antioxidant activity which can mitigate this neurotoxicity. The present study investigated the possible protective effect of SALEE on MSG-induced toxicity in rats. Twenty-six ...

  12. Unripe Musa paradisiacal fruit diet ameliorates impaired glucose ...

    African Journals Online (AJOL)

    Excess iron impairs glucose regulatory mechanisms through an increase in oxidative stress. Unripe Musa paradisiaca fruit (UMP) diets have been reported to alleviate diabetes and exert antioxidant effects. In this study, some glucose regulatory indices were investigated in Wistar rats with iron-induced oxidative stress and ...

  13. Camel milk ameliorates steatohepatitis, insulin resistance and lipid peroxidation in experimental non-alcoholic fatty liver disease.

    Science.gov (United States)

    Korish, Aida A; Arafah, Maha M

    2013-10-13

    Camel milk (CM) is gaining increasing recognition due to its beneficial effects in the control and prevention of multiple health problems. The current study aimed to investigate the effects of CM on the hepatic biochemical and cellular alterations induced by a high-fat, cholesterol-rich diet (HCD), specifically, non-alcoholic fatty liver disease (NAFLD). Seventy male Wistar rats were divided into four groups: the Control (C) Group fed a standard diet; the Control + camel milk (CCM) Group fed a standard diet and CM, the Cholesterol (Ch) Group fed a HCD with no CM, and the Cholesterol + camel milk (ChM) Group fed a HCD and CM. The following parameters were investigated in the studied groups; basal, weekly random and final fasting blood glucose levels, intraperitoneal glucose tolerance test (GTT) and insulin tolerance test (ITT), serum insulin, serum lipids, liver functions, lipid peroxidation products, the antioxidant activity of catalase (CAT) and the levels of reduced glutathione (GSH). In addition, HOMA-IR as an index of insulin resistance (IR) and the histopathology of the hepatic tissue were assessed. The Ch Group developed features similar to those of non-alcoholic steatohepatitis (NASH), characterized by hepatic steatosis; inflammatory cellular infiltration in liver tissue; altered liver functions; and increased total cholesterol, triglycerides, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, atherogenic index (AI), blood glucose, IR, and malondialdehyde (MDA) levels. Additionally, feeding the HCD to animals in the Ch Group decreased CAT activity and the GSH and high-density lipoprotein (HDL) cholesterol levels. Camel milk intake for eight weeks decreased hepatic fat accumulation and inflammatory cellular infiltration, preserved liver function, increased the GSH levels and CAT activity, decreased the MDA levels, and ameliorated the changes in the lipid profile, AI, and IR in animals from the ChM Group. CM has a unique composition

  14. Proteasome inhibition induces both antioxidant and hb f responses in sickle cell disease via the nrf2 pathway.

    Science.gov (United States)

    Pullarkat, Vinod; Meng, Zhuo; Tahara, Stanley M; Johnson, Cage S; Kalra, Vijay K

    2014-01-01

    Oxidant stress is implicated in the manifestations of sickle cell disease including hemolysis and vascular occlusion. Strategies to induce antioxidant response as well as Hb F (α2γ2) have the potential to ameliorate the severity of sickle cell disease. Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or Nrf2) is a transcription factor that regulates antioxidant enzymes as well as γ-globin transcription. The Nrf2 in the cytoplasm is bound to its adapter protein Keap-1 that targets Nrf2 for proteasomal degradation, thereby preventing its nuclear translocation. We examined whether inhibiting the 26S proteasome using the clinically applicable proteasome inhibitors bortezomib and MLN 9708 would promote nuclear translocation of Nrf2, and thereby induce an antioxidant response and as well as Hb F in sickle cell disease. Proteasome inhibitors induced reactive oxygen species (ROS) and thereby increased Nrf2-dependent antioxidant enzyme transcripts, elevated cellular glutathione (GSH) levels and γ-globin transcripts as well as Hb F levels in the K562 cell line and also in erythroid burst forming units (BFU-E) generated from peripheral blood mononuclear cells of sickle cell disease patients. These responses were abolished by siRNA-mediated knockdown of Nrf2. Proteasome inhibitors, especially newer oral agents such as MLN9708 have the potential to be readily translated to clinical trials in sickle cell disease with the dual end points of antioxidant response and Hb F induction.

  15. ANTIOXIDANT POTENCY OF WATER KEFIR

    Directory of Open Access Journals (Sweden)

    Muneer Alsayadi M.S.

    2013-06-01

    Full Text Available Reactive oxygen species (ROS have strong relationship with several diseases. Many fermented foods were reported to be important sources for antioxidant compounds. Antioxidant activity of water kefir never reported in the scientific literature. The objective of this study was to detect and investigate the antioxidant potency of water kefir. Water kefir was prepared by fermentation of sugar solution with kefir grains for 24h. Antioxidant activity of fresh water kefir drink and its extract with (0.125–5 mg/ml was evaluated using 2,2,-diphenyl-1-pricrylhydrozyl (DPPH scavenging method, and inhibition of ascorbate autoxidation and the reducing power of water kefir were determined, Butylated hydroxyanisole (BHA and ascorbic acid were used for comparison. Water kefir demonstrated great ability to DPPH scavenging ranged (9.88-63.17%. And inhibit ascorbate oxidation by (6.08-25.57% increased in consequent with concentration raising. These results prime to conclude that water kefir could be promisor source of natural antioxidants with good potency in health developing.

  16. Incremental Beliefs About Ability Ameliorate Self-Doubt Effects

    Directory of Open Access Journals (Sweden)

    Qin Zhao

    2015-12-01

    Full Text Available Past research has typically shown negative effects of self-doubt on performance and psychological well-being. We suggest that these self-doubt effects largely may be due to an underlying assumption that ability is innate and fixed. The present research investigated the main hypothesis that incremental beliefs about ability might ameliorate negative effects of self-doubt. We examined our hypotheses using two lab tasks: verbal reasoning and anagram tasks. Participants’ self-doubt was measured and beliefs about ability were measured after participants read articles advocating either for incremental or entity theories of ability. American College Testing (ACT scores were obtained to index actual ability level. Consistent with our hypothesis, for participants who believed ability was relatively fixed, higher self-doubt was associated with increased negative affect and lower task performance and engagement. In contrast, for participants who believed that ability was malleable, negative self-doubt effects were ameliorated; self-doubt was even associated with better task performance. These effects were further moderated by participants’ academic ability. These findings suggest that mind-sets about ability moderate self-doubt effects. Self-doubt may have negative effects only when it is interpreted as signaling that ability is immutably low.

  17. Guanfacine ameliorates hypobaric hypoxia induced spatial working memory deficits.

    Science.gov (United States)

    Kauser, H; Sahu, S; Kumar, S; Panjwani, U

    2014-01-17

    Hypobaric hypoxia (HH) observed at high altitude causes mild cognitive impairment specifically affecting attention and working memory. Adrenergic dysregulation and neuronal damage in prefrontal cortex (PFC) has been implicated in hypoxia induced memory deficits. Optimal stimulation of alpha 2A adrenergic receptor in PFC facilitates the spatial working memory (SWM) under the conditions of adrenergic dysregulation. Therefore the present study was designed to test the efficacy of alpha 2A adrenergic agonist, Guanfacine (GFC), to restore HH induced SWM deficits and PFC neuronal damage. The rats were exposed to chronic HH equivalent to 25,000ft for 7days in an animal decompression chamber and received daily treatment of GFC at a dose of 1mg/kg body weight via the intramuscular route during the period of exposure. The cognitive performance was assessed by Delayed Alternation Task (DAT) using T-Maze and PFC neuronal damage was studied by apoptotic and neurodegenerative markers. Percentage of correct choice decreased significantly while perseverative errors showed a significant increase after 7days HH exposure, GFC significantly ameliorated the SWM deficits and perseveration. There was a marked and significant increase in chromatin condensation, DNA fragmentation, neuronal pyknosis and fluoro Jade positive cells in layer II of the medial PFC in hypoxia exposed group, administration of GFC significantly reduced the magnitude of these changes. Modulation of adrenergic mechanisms by GFC may serve as an effective countermeasure in amelioration of prefrontal deficits and neurodegenerative changes during HH. © 2013.

  18. Phytoceramide Shows Neuroprotection and Ameliorates Scopolamine-Induced Memory Impairment

    Directory of Open Access Journals (Sweden)

    Seikwan Oh

    2011-10-01

    Full Text Available The function and the role phytoceramide (PCER and phytosphingosine (PSO in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o. recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

  19. Phytoceramide shows neuroprotection and ameliorates scopolamine-induced memory impairment.

    Science.gov (United States)

    Jung, Jae-Chul; Lee, Yeonju; Moon, Sohyeon; Ryu, Jong Hoon; Oh, Seikwan

    2011-10-28

    The function and the role phytoceramide (PCER) and phytosphingosine (PSO) in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS) showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o.) recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer's disease.

  20. Arginase Inhibition Ameliorates Hepatic Metabolic Abnormalities in Obese Mice

    Science.gov (United States)

    Moon, Jiyoung; Do, Hyun Ju; Cho, Yoonsu; Shin, Min-Jeong

    2014-01-01

    Objectives We examined whether arginase inhibition influences hepatic metabolic pathways and whole body adiposity in diet-induced obesity. Methods and Results After obesity induction by a high fat diet (HFD), mice were fed either the HFD or the HFD with an arginase inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA). Nor-NOHA significantly prevented HFD-induced increases in body, liver, and visceral fat tissue weight, and ameliorated abnormal lipid profiles. Furthermore, nor-NOHA treatment reduced lipid accumulation in oleic acid-induced hepatic steatosis in vitro. Arginase inhibition increased hepatic nitric oxide (NO) in HFD-fed mice and HepG2 cells, and reversed the elevated mRNA expression of hepatic genes in lipid metabolism. Expression of phosphorylated 5′ AMPK-activated protein kinase α was increased by arginase inhibition in the mouse livers and HepG2 cells. Conclusions Arginase inhibition ameliorated obesity-induced hepatic lipid abnormalities and whole body adiposity, possibly as a result of increased hepatic NO production and subsequent activation of metabolic pathways involved in hepatic triglyceride metabolism and mitochondrial function. PMID:25057910

  1. Gemigliptin ameliorates Western-diet-induced metabolic syndrome in mice.

    Science.gov (United States)

    Choi, Seung Hee; Leem, Jaechan; Park, Sungmi; Lee, Chong-Kee; Park, Keun-Gyu; Lee, In-Kyu

    2017-02-01

    Dipeptidyl peptidase 4 (DPP-4) inhibitors are widely used antihyperglycemic agents for type 2 diabetes mellitus. Recently, increasing attention has been focused on the pleiotropic actions of DPP-4 inhibitors. The aim of the present study was to examine whether gemigliptin, a recently developed DPP-4 inhibitor, could ameliorate features of metabolic syndrome. Mice were fed a Western diet (WD) for 12 weeks and were subsequently divided into 2 groups: mice fed a WD diet alone or mice fed a WD diet supplemented with gemigliptin for an additional 4 weeks. Gemigliptin treatment attenuated WD-induced body mass gain, hypercholesterolemia, adipocyte hypertrophy, and macrophage infiltration into adipose tissue, which were accompanied by an increased expression of uncoupling protein 1 in subcutaneous fat. These events contributed to improved insulin sensitivity, as assessed by the homeostasis model assessment of insulin resistance and intraperitoneal insulin tolerance test. Furthermore, gemigliptin reduced WD-induced hepatic triglyceride accumulation via inhibition of de novo lipogenesis and activation of fatty acid oxidation, which was accompanied by AMP-dependent protein kinase activation. Gemigliptin ameliorated WD-induced hepatic inflammation and fibrosis through suppression of oxidative stress. These results suggest that DPP-4 inhibitors may represent promising therapeutic agents for metabolic syndrome beyond their current role as antihyperglycemic agents.

  2. Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals

    Science.gov (United States)

    Baek, Kwangyeol; Tait, Roger; Elliott, Rebecca; Ersche, Karen D.; Flechais, Remy; McGonigle, John; Murphy, Anna; Nestor, Liam J.; Orban, Csaba; Passetti, Filippo; Paterson, Louise M.; Rabiner, Ilan; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor M.; Bullmore, Edward T.; Lingford‐Hughes, Anne R.; Deakin, Bill; Nutt, David J.; Sahakian, Barbara J.; Robbins, Trevor W.; Voon, Valerie

    2017-01-01

    Abstract Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50‐mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly‐drug‐dependent individuals compared with 36 healthy volunteers. Graph theoretic and network‐based statistical analysis of resting‐state functional magnetic resonance imaging (MRI) data revealed that alcohol‐dependent subjects had reduced functional connectivity of a dispersed network compared with both poly‐drug‐dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol‐dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly‐substance‐dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology. PMID:28247526

  3. Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats

    OpenAIRE

    Niwa, Atsuko; Tajiri, Takashi; Higashino, Hideaki

    2011-01-01

    Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg−1 d−1), Agaricus blazei (1 g kg−1 d−1) or Smallanthus sonchifolius (4 g kg−1 d−1) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed ...

  4. Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Niwa, Atsuko; Tajiri, Takashi; Higashino, Hideaki

    2011-05-01

    Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg(-1) d(-1)), Agaricus blazei (1 g kg(-1) d(-1)) or Smallanthus sonchifolius (4 g kg(-1) d(-1)) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed the increases of fasting plasma glucose and hemoglobin A1c levels, and restored body weight loss during diabetes. Serum insulin levels after oral glucose administration tests increased along the treatments of Ipomoea batatas or Agaricus blazei. Moreover, Ipomoea batatas and Agaricus blazei reduced superoxide production from leukocytes and vascular homogenates, serum 8-oxo-2'-deoxyguanosine, and vascular nitrotyrosine formation of diabetic rats to comparable levels of normal control animals. Stress- and inflammation-related p38 mitogen-activated protein kinase activity and tumor necrosis factor-α production of diabetic rats were significantly depressed by Ipomoea batatas administration. Histological examination also exhibited improvement of pancreatic β-cells mass after treatments with Ipomoea batatas or Agaricus blazei. These results suggest that hypoglycemic effects of Ipomoea batatas or Agaricus blazei result from their suppression of oxidative stress and proinflammatory cytokine production followed by improvement of pancreatic β-cells mass.

  5. Ameliorative Effect of Zinc Oxide Nanoparticles on Antioxidants and Sperm Characteristics in Streptozotocin-Induced Diabetic Rat Testes

    Science.gov (United States)

    Afifi, Mohamed; Almaghrabi, Omar A.; Kadasa, Naif Mohammed

    2015-01-01

    The present study investigated the impact of zinc oxide nanoparticles (ZnONPs) on the oxidative status and sperm characteristics in diabetic rat testicular tissue. Forty male albino rats were used in this study; 10 of them served as a control and 30 rats were injected with a single dose (100 mg/kg) of streptozotocin intraperitoneally. They were subdivided into diabetic, diabetic + ZnONPs (10 mg/kg B.W.), and diabetic and cotreated with ZnONPs + insulin groups. The sperm count and motility were assessed. The activity and mRNA expression of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GRD), and Glutathion-S-Transferase (GST) were determined in the testicular tissue. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated in the testicular tissue. Sperm count and motility increased in ZnONPs treated diabetic rats. A significant increase in the activity and mRNA expression of SOD, CAT, GPx, GRD, and GST was shown in ZnONPs treated diabetic rats. MDA significantly decreased, while GSH increased in testicular tissue of ZnONPs treated diabetic rats. It was concluded that ZnONPs either alone or in combination with insulin have the ability to increase the sperm count and motility and protect the testicular tissue against the oxidative stress induced by diabetes in rats. PMID:26581756

  6. Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats

    Science.gov (United States)

    Niwa, Atsuko; Tajiri, Takashi; Higashino, Hideaki

    2011-01-01

    Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg−1 d−1), Agaricus blazei (1 g kg−1 d−1) or Smallanthus sonchifolius (4 g kg−1 d−1) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed the increases of fasting plasma glucose and hemoglobin A1c levels, and restored body weight loss during diabetes. Serum insulin levels after oral glucose administration tests increased along the treatments of Ipomoea batatas or Agaricus blazei. Moreover, Ipomoea batatas and Agaricus blazei reduced superoxide production from leukocytes and vascular homogenates, serum 8-oxo-2'-deoxyguanosine, and vascular nitrotyrosine formation of diabetic rats to comparable levels of normal control animals. Stress- and inflammation-related p38 mitogen-activated protein kinase activity and tumor necrosis factor-α production of diabetic rats were significantly depressed by Ipomoea batatas administration. Histological examination also exhibited improvement of pancreatic β-cells mass after treatments with Ipomoea batatas or Agaricus blazei. These results suggest that hypoglycemic effects of Ipomoea batatas or Agaricus blazei result from their suppression of oxidative stress and proinflammatory cytokine production followed by improvement of pancreatic β-cells mass. PMID:21562638

  7. The proper time for antioxidant consumption.

    Science.gov (United States)

    Beaulieu, Michaël; Schaefer, H Martin

    2014-04-10

    Consuming food rich in antioxidants may help organisms to increase their antioxidant defences and avoid oxidative damage. Under the hypothesis that organisms actively consume food for its antioxidant properties, they would need to do so in view of other physiological requirements, such as energy requirements. Here, we observed that Gouldian finches (Erythrura gouldiae) consumed most seeds rich in antioxidants in the middle of the day, while their consumption of staple seeds more profitable in energy intake (and poor in antioxidants) was maximal in the morning and the evening. This consumption of seeds rich in antioxidants in the middle of the day may be explicable (1) because birds took advantage of a time window associated with relaxed energy requirements to ingest antioxidant resources, or (2) because birds consumed antioxidant resources as a response to the highest antioxidant requirements in the middle of the day. If the latter hypothesis holds true, having the possibility to ingest antioxidants should be most beneficial in terms of oxidative balance in the middle of the day. Even though feeding on seeds rich in antioxidants improved Gouldian finches' overall antioxidant capacity, we did not detect any diurnal effect of antioxidant intake on plasma oxidative markers (as measured by the d-ROM and the OXY-adsorbent tests). This indicates that the diurnal pattern of antioxidant intake that we observed was most likely constrained by the high consumption of staple food to replenish or build up body reserves in the morning and in the evening, and not primarily determined by elevated antioxidant requirements in the middle of the day. Consequently, animals appear to have the possibility to increase antioxidant defences by selecting food rich in antioxidants, only when energetic constraints are relaxed. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. 75 FR 58415 - Prospective Grant of Exclusive License: Prevention, Prophylaxis, Cure, Amelioration, and/or...

    Science.gov (United States)

    2010-09-24

    ... Exclusive License: Prevention, Prophylaxis, Cure, Amelioration, and/or Treatment of Infection and/or the... dengue virus, characterized by rash, high fever, and severe, sometimes persistent arthritis. The field of use may be limited to ``Prevention, prophylaxis, cure, amelioration, and/or treatment of infection and...

  9. Antioxidant and antimicrobial activities of polyphenols from ...

    African Journals Online (AJOL)

    USER

    2010-05-17

    May 17, 2010 ... The antioxidant properties and antimicrobial potential of three ethnomedicinal plants, (Momordica charanta, Senna alata and Nauclea lafifolia) extracted with acetone were investigated. Polyphenols from the medicinal plants were screened for their antioxidant and antimicrobial activities against pathogenic.

  10. Antioxidant and antimicrobial activities of polyphenols from ...

    African Journals Online (AJOL)

    the medicinal plants were screened for their antioxidant and antimicrobial activities against pathogenic micro organisms (Staphylococcus aureus, Streptococcus pyogenes, Esherichia coli and Candida albicans). The medicinal plants displayed different polyphenols contents and antioxidant activities. In addition, varying ...

  11. Proximate and Phytochemical composition and antioxidant ...

    African Journals Online (AJOL)

    Conclusion: Indigenous landraces of Omani fenugreek seeds are a rich source of protein, dietary fiber, and many important bioactive components, which were found to be significantly correlatedwith its antioxidant properties. Keywords: Omani fenugreek, landraces, phytochemical composition, antioxidant properties.

  12. Antioxidant and antibacterial activities of polyphenols from ...

    African Journals Online (AJOL)

    Polyphenols from four medicinal plants of Burkina Faso, Combretum micranthum, Khaya senegalensis, Pterocarpus erinaceus and Sida acuta, were screened for their antioxidant and antimicrobial activities against pathogenic bacteria. The medicinal plants displayed different polyphenols contents and antioxidant activities.

  13. Antioxidant food supplements in human health

    National Research Council Canada - National Science Library

    Hiramatsu, Midori; Packer, Lester; Yoshikawa, Toshikazu

    1999-01-01

    ... of many of nature's antioxidant substances; grapes: starting source for red wine production; rich in antioxidants; onions: rich source of the bioflavonoid quercetin. This book is printed on acid-...

  14. Cosmeceutical values, antimicrobial activities and antioxidant ...

    African Journals Online (AJOL)

    Jane

    2011-10-24

    Oct 24, 2011 ... Key words: Antimicrobial, antioxidant, ethanol extract, water extract, cashew leaves, cosmeceutical. INTRODUCTION ... Anacardium occidentale (Cashew) leaves extract could ..... Antioxidant activity at different contact time for treatment of different concentration CLE in water with different amount of GAC.

  15. Curcumin and Quercetin Ameliorated Cypermethrin and Deltamethrin-Induced Reproductive System Impairment in Male Wistar Rats by Upregulating The Activity of Pituitary-Gonadal Hormones and Steroidogenic Enzymes.

    Science.gov (United States)

    Sharma, Poonam; Aslam Khan, Irshad; Singh, Rambir

    2018-04-01

    Dietary antioxidants protect tissues and organs against insecticides/xenobiotic-induced damage. In the present study, we evaluated the results of exposure to synthetic pyrethroid insecticides, cypermethrin (Cyp) and deltamethrin (Del) and possible protective effects of curcumin and quercetin on reproductive system in male Wistar rats. In this controlled experimental study, 42 male Wistar rats were randomly divided into 7 groups of 6 animals. Group A served as control, group B was exposed to Cyp (2 mg/kg.bw), group C was exposed to Del (2 mg/kg.bw), group D was exposed to Cyp+Del (2 mg/kg.bw each), group E was exposed to Cyp+Del and treated with curcumin (100 mg/kg.bw), group F was exposed to Cyp+Del and treated with quercetin (100 mg/kg.bw) and group G was exposed to Cyp+Del and treated with quercetin+curcumin for 45 days. Exposure to Cyp and Del caused decreases in reproductive organs weight, sperm count, sperm motility, level of sex hormones viz. testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH), steroidogenic enzymes viz. 3β-hydroxyl steroid dehydrogenase (3β-HSD) and 17β-HSD, non-enzymatic antioxidant glutathione (GSH) and enzymatic antioxidants viz. superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) activity and increases in sperm abnormalities and lipid peroxidation (LPO). The exposure also adversely affected the histo-achitecture of testes. Single and combined treatment with curcumin and quercetin significantly ameliorated Cyp and Del-induced damage in reproductive system. Curcumin and quercetin protected against Cyp and Del-induced reproductive system toxicity and oxidative damage in rats. The increases in activities of 3β-HSD and 17β-HSD with concomitant increases in testosterone were mainly responsible for ameliorating effects of curcumin and quercetin. Curcumin showed slightly better activity as compared to quercetin. The combination

  16. Antioxidant properties of catechins: Comparison with other antioxidants.

    Science.gov (United States)

    Grzesik, Michalina; Naparło, Katarzyna; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

    2018-02-15

    Antioxidant properties of five catechins and five other flavonoids were compared with several other natural and synthetic compounds and related to glutathione and ascorbate as key endogenous antioxidants in several in vitro tests and assays involving erythrocytes. Catechins showed the highest ABTS-scavenging capacity, the highest stoichiometry of Fe 3+ reduction in the FRAP assay and belonged to the most efficient compounds in protection against SIN-1 induced oxidation of dihydrorhodamine 123, AAPH-induced fluorescein bleaching and hypochlorite-induced fluorescein bleaching. Glutathione and ascorbate were less effective. (+)-catechin and (-)-epicatechin were the most effective compounds in protection against AAPH-induced erythrocyte hemolysis while (-)-epicatechin gallate, (-)-epigallocatechin gallate and (-)-epigallocatechin protected at lowest concentrations against hypochlorite-induced hemolysis. Catechins [(-)-epigallocatechin gallate and (-)-epicatechin gallate)] were most efficient in the inhibition of AAPH-induced oxidation of 2'7'-dichlorodihydroflurescein contained inside erythrocytes. Excellent antioxidant properties of catechins and other flavonoids make them ideal candidates for nanoformulations to be used in antioxidant therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Exogenous Application of Citric Acid Ameliorates the Adverse Effect of Heat Stress in Tall Fescue (Lolium arundinaceum)

    Science.gov (United States)

    Hu, Longxing; Zhang, Zhifei; Xiang, Zuoxiang; Yang, Zhijian

    2016-01-01

    Citric acid may be involved in plant response to high temperature. The objective of this study was to investigate whether exogenous citric acid could improve heat tolerance in a cool-season turfgrass species, tall fescue (Lolium arundinaceum), and to determine the physiological mechanisms of citric acid effects on heat stress tolerance. The grasses were subjected to four citric acid levels (0, 0.2, 2, and 20 mM) and two temperature levels (25/20 and 35/30 ± 0.5°C, day/night) treatments in growth chambers. Heat stress increased an electrolyte leakage (EL) and malonaldehyde (MDA) content, while reduced plant growth, chlorophyll (Chl) content, photochemical efficiency (Fv/Fm), root activity and antioxidant enzyme activities (superoxide dismutase, SOD; catalase, CAT; peroxidase, POD). External citric acid alleviated the detrimental effects of heat stress on tall fescue, which was evidenced by decreased EL and MDA content, and improved plant growth under stress conditions. Additionally, the reduction in Chl content, Fv/Fm, SOD, POD, CAT and root activity were ameliorated in citric acid treated plants under heat stressed conditions. High temperature induced the expression of heat shock protein (HSP) genes, which exhibited greater expression levels after citric acid treatment under heat stress. These results suggest that exogenous citric acid application may alleviate growth and physiological damage caused by high temperature. In addition, the exogenously applied citric acid might be responsible for maintaining membrane stability, root activity, and activation of antioxidant response and HSP genes which could contribute to the protective roles of citric acid in tall fescue responses to heat stress. PMID:26925085

  18. Exogenous Application of Citric Acid Ameliorates the Adverse Effect of Heat Stress in Tall Fescue (Lolium arundinaceum).

    Science.gov (United States)

    Hu, Longxing; Zhang, Zhifei; Xiang, Zuoxiang; Yang, Zhijian

    2016-01-01

    Citric acid may be involved in plant response to high temperature. The objective of this study was to investigate whether exogenous citric acid could improve heat tolerance in a cool-season turfgrass species, tall fescue (Lolium arundinaceum), and to determine the physiological mechanisms of citric acid effects on heat stress tolerance. The grasses were subjected to four citric acid levels (0, 0.2, 2, and 20 mM) and two temperature levels (25/20 and 35/30 ± 0.5°C, day/night) treatments in growth chambers. Heat stress increased an electrolyte leakage (EL) and malonaldehyde (MDA) content, while reduced plant growth, chlorophyll (Chl) content, photochemical efficiency (Fv/Fm), root activity and antioxidant enzyme activities (superoxide dismutase, SOD; catalase, CAT; peroxidase, POD). External citric acid alleviated the detrimental effects of heat stress on tall fescue, which was evidenced by decreased EL and MDA content, and improved plant growth under stress conditions. Additionally, the reduction in Chl content, Fv/Fm, SOD, POD, CAT and root activity were ameliorated in citric acid treated plants under heat stressed conditions. High temperature induced the expression of heat shock protein (HSP) genes, which exhibited greater expression levels after citric acid treatment under heat stress. These results suggest that exogenous citric acid application may alleviate growth and physiological damage caused by high temperature. In addition, the exogenously applied citric acid might be responsible for maintaining membrane stability, root activity, and activation of antioxidant response and HSP genes which could contribute to the protective roles of citric acid in tall fescue responses to heat stress.

  19. Exogenous Application of Citric Acid Ameliorates the Adverse Effect of Heat Stress in Tall Fescue (Festuca arundinacea

    Directory of Open Access Journals (Sweden)

    Longxing eHu

    2016-02-01

    Full Text Available Citric acid may be involved in plant response to high temperature. The objective of this study was to investigate whether exogenous citric acid could improve heat tolerance in a cool‐season turfgrass species, tall fescue (Lolium arundinaceum, and to determine the physiological mechanisms of citric acid effects on heat stress tolerance. The grasses were subjected to four citric acid levels (0, 0.2, 2 and 20 mM and two temperature levels (25/20 and 35/30 ± 0.5 ̊C, day/night treatments in growth chambers. Heat stress increased an electrolyte leakage (EL and malonaldehyde (MDA content, while reduced plant growth, chlorophyll (Chl content, photochemical efficiency (Fv/Fm, root activity and antioxidant enzyme activities (superoxide dismutase, SOD; catalase, CAT; peroxidase, POD. External citric acid alleviated the detrimental effects of heat stress on tall fescue, which was evidenced by decreased EL and MDA content, and improved plant growth under stress conditions. Additionally, the reduction in Chl content, Fv/Fm, SOD, POD, CAT and root activity were ameliorated in citric acid treated plants under heat stressed conditions. High temperature induced the expression of heat shock protein (HSP genes, which exhibited greater expression levels after citric acid treatment under heat stress. These results suggest that exogenous citric acid application may alleviate growth and physiological damage caused by high temperature. In addition, the exogenously applied citric acid might be responsible for maintaining membrane stability, root activity, and activation of antioxidant response and HSP genes which could contribute to the protective roles of citric acid in tall fescue responses to heat stress.

  20. Ameliorating Role of Lycopene, Tomato Puree, and Spirulina + Tomato Puree on the Hematology of Fluoride-Exposed Swiss Albino Mice.

    Science.gov (United States)

    Sharma, Shweta; Parashar, Puneet; Sharma, Subhasini; Sharma, Kanta Prasad

    2018-01-16

    Plant species rich in antioxidants (vitamins, flavonoids, lignans, and carotenoids) have been explored for complementary therapy of chronic diseases (cancers, coronary heart disease) and mitigation of pollutant toxicity. This article investigates their ameliorative role on selective hematological and serum biochemical parameters in fluoride-exposed (190 mg/kg body weight) Swiss albino mice pretreated with the antioxidant-rich diet supplements tomato puree (with and without peels), spirulina (cyanobacteria), and lycopene (present in tomato) for 45 days prior to entry into experimental protocol. Compared with standard feed control, diet-modulated controls had more hairy and lustrous white fur, hemodilution, increase in platelet counts (2- to 5-fold), red blood cell (RBC) size (11%-14%), mean corpuscular hemoglobin (Hb) concentration (MCHC; 5%-14%), and serum albumin (23%-27%). Fluoride-exposed mice reared on standard feed had less hairy, pale white, lusterless fur and black nails, reduction in RBC and white blood cell (WBC) counts and Hb content, and morphological abnormalities in RBCs (poikilocytosis). By contrast, fur quality of fluoride-treated diet-modulated groups was similar to standard feed control; counts and morphology of their RBCs and Hb content similar to the respective controls, and increase in WBC counts greater than controls. In comparison to the fluoride-treated standard feed group, platelet counts were higher in the treated mice of the diet-modulated groups. This study thus revealed the hemoprotective role of diet supplements in fluoride-treated mice. Considering the prevalence of fluoride-induced chronic toxicity in developing countries, our findings have relevance in minimizing hematological disorders among people residing in the fluoride-affected areas, because indigenously cultivated low-price tomato fruits are easily available for consumption.

  1. Quercetin ameliorates imiquimod-induced psoriasis-like skin inflammation in mice via the NF-κB pathway.

    Science.gov (United States)

    Chen, Haiming; Lu, Chuanjian; Liu, Huazhen; Wang, Maojie; Zhao, Hui; Yan, Yuhong; Han, Ling

    2017-07-01

    Quercetin (QC) is a dietary flavonoid abundant in many natural plants. A series of studies have shown that it has been shown to exhibit several biological properties, including anti-inflammatory, anti-oxidant, cardio-protective, vasodilatory, liver-protective and anti-cancer activities. However, so far the possible therapeutic effect of QC on psoriasis has not been reported. The present study was undertaken to evaluate the potential beneficial effect of QC in psoriasis using a generated imiquimod (IMQ)-induced psoriasis-like mouse model, and to further elucidate its underlying mechanisms of action. Effects of QC on PASI scores, back temperature, histopathological changes, oxidative/anti-oxidative indexes, pro-inflammatory cytokines and NF-κB pathway in IMQ-induced mice were investigated. Our results showed that QC could significantly reduce the PASI scores, decrease the temperature of the psoriasis-like lesions, and ameliorate the deteriorating histopathology in IMQ-induced mice. Moreover, QC effectively attenuated levels of TNF-α, IL-6 and IL-17 in serum, increased activities of GSH, CAT and SOD, and decreased the accumulation of MDA in skin tissue induced by IMQ in mice. The mechanism may be associated with the down-regulation of NF-κB, IKKα, NIK and RelB expression and up-regulation of TRAF3, which were critically involved in the non-canonical NF-κB pathway. In conclusion, our present study demonstrated that QC had appreciable anti-psoriasis effects in IMQ-induced mice, and the underlying mechanism may involve the improvement of antioxidant and anti-inflammatory status and inhibition on the activation of the NF-κB signaling. Hence, QC, a naturally occurring flavone with potent anti-psoriatic effects, has the potential for further development as a candidate for psoriasis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Antioxidants: Characterization, natural sources, extraction and analysis

    OpenAIRE

    OROIAN, MIRCEA; Escriche Roberto, Mª Isabel

    2015-01-01

    [EN] Recently many review papers regarding antioxidants fromdifferent sources and different extraction and quantification procedures have been published. However none of them has all the information regarding antioxidants (chemistry, sources, extraction and quantification). This article tries to take a different perspective on antioxidants for the new researcher involved in this field. Antioxidants from fruit, vegetables and beverages play an important role in human health, fo...

  3. Partitioning of selected antioxidants in mayonnaise

    DEFF Research Database (Denmark)

    Jacobsen, Charlotte; Schwarz, K.; Stockmann, H.

    1999-01-01

    This study examined partitioning of alpha-, beta-, and gamma- tocopherol and six polar antioxidants (Trolox, ferulic acid, caffeic acid, propyl gallate, gallic acid, and catechin) in mayonnaise. Partitioning of antioxidants between different phases was determined after separation of mayonnaise...... by either (a) centrifugation + ultracentrifugation or (b) centrifugation + dialysis. Antioxidants partitioned in accordance with their chemical structure and polarity: Tocopherols were concentrated in the oil phase (93-96%), while the proportion of polar antioxidants in the oil phase ranged from 0% (gallic...

  4. Antiradical and antioxidant activities of new bio-antioxidants.

    Science.gov (United States)

    Kancheva, V D; Saso, L; Angelova, S E; Foti, M C; Slavova-Kasakova, A; Daquino, C; Enchev, V; Firuzi, O; Nechev, J

    2012-02-01

    Antioxidants could be promising agents for management of oxidative stress-related diseases. New biologically active compounds, belonging to a rare class of natural lignans with antiangiogenic, antitumoral and DNA intercalating properties, have been recently synthesized. These compounds are benzo[kl]xanthene lignans (1,2) and dihydrobenzofuran neolignans (3,4). The radical scavenging and chain-breaking antioxidant activities of compounds 1-4 were studied by applying different methods: radical scavenging activity by DPPH rapid test, chain-breaking antioxidant activity and quantum chemical calculations. All studied compounds were found to be active as DPPH scavengers but reaction time with DPPH and compounds' concentrations influenced deeply the evaluation. The highest values of radical scavenging activity (%RSAmax) and largest rate constants for reaction with DPPH were obtained for compounds 2 and 3. Comparison of %RSAmax with that of standard antioxidants DL-α-tocopherol (TOH), caffeic acid (CA) and butylated hydroxyl toluene (BHT) give the following new order of %RSA max: TOH (61.1%) > CA (58.6%) > 3 (36.3%) > 2 (28.1%) > 4 (6.7%) > 1 (3.6%) = BHT (3.6%). Chain-breaking antioxidant activities of individual compounds (0.1-1.0 mM) and of their equimolar binary mixtures (0.1 mM) with TOH were determined from the kinetic curves of lipid autoxidation at 80 °C. On the basis of a comparable kinetic analysis with standard antioxidants a new order of the antioxidant efficiency (i.e., protection factor, PF) of compounds 1-4 were obtained: 2 (7.2) ≥ TOH (7.0) ≥ CA (6.7) > 1 (3.1) > 3 (2.2) > ferulic acid FA (1.5) > 4 (0.6); and of the antioxidant reactivity (i.e. inhibition degree, ID): 2 (44.0) > TOH (18.7) > CA (9.3) > 1 (8.4) > 3 (2.8) > FA (1.0) > 4 (0.9). The important role of the catecholic structure in these compounds, which is responsible for the high chain-breaking antioxidant activity, is discussed and a reaction

  5. 1,4-Naphthoquinone, a pro-oxidant, ameliorated radiation induced gastro-intestinal injury through perturbation of cellular redox and activation of Nrf2 pathway.

    Science.gov (United States)

    Gambhir, Lokesh

    Detrimental effects of ionizing radiation (IR) are observed at the doses above 1 Gy. Treatment modalities are available up to doses of 6 Gy including bonemarrow transplantation and administration of antibiotics. However, exposure to IR doses above 8 Gy results in gastro-intestinal (GI) syndrome characterised by denudated villi, apoptosis of crypt cells and elevated inflammatory responses. Multiple strategies have been employed to investigate novel agents to protect against IR induced injury. Since cellular redox homeostasis plays a pivotal role in deciding the cell fate, present study was undertaken to explore the potential of 1,4-naphthoquinone (NQ), a pro-oxidant, to ameliorate IR induced GI syndrome. NQ protected INT 407 cells against IR induced cell death of intestinal epithelial cells in vitro. NQ induced perturbation in cellular redox status and induced the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. Thiol antioxidant and inhibitors of Nrf2 pathway abrogated the radioprotection offered by NQ. Further, knocking down Nrf2 rescind the NQ mediated protection against IR induced cell death. In conclusion, NQ protects against IR radiation induced GI syndrome in vitro by perturbing cellular redox and activating Nrf2 pathway. This is the first report highlighting the potential of a pro-oxidant to ameliorate IR induced GI injury.

  6. Astragalus membranaceus-Polysaccharides Ameliorates Obesity, Hepatic Steatosis, Neuroinflammation and Cognition Impairment without Affecting Amyloid Deposition in Metabolically Stressed APPswe/PS1dE9 Mice

    Directory of Open Access Journals (Sweden)

    Yung-Cheng Huang

    2017-12-01

    Full Text Available Astragalus membranaceus is commonly used in traditional Chinese medicine for strengthening the host defense system. Astragalus membranaceus-polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine the effects of Astragalus membranaceus-polysaccharides on metabolically stressed transgenic mice in order to develop this macromolecules for treatment of sporadic Alzheimer’s disease, a neurodegenerative disease with metabolic risk factors. Transgenic mice, at 10 weeks old prior to the appearance of senile plaques, were treated in combination of administrating high-fat diet and injecting low-dose streptozotocin to create the metabolically stressed mice model. Astragalus membranaceus-polysaccharides was administrated starting at 14 weeks for 7 weeks. We found that Astragalus membranaceus-polysaccharides reduced metabolic stress-induced increase of body weight, insulin and insulin and leptin level, insulin resistance, and hepatic triglyceride. Astragalus membranaceus-polysaccharides also ameliorated metabolic stress-exacerbated oral glucose intolerance, although the fasting blood glucose was only temporally reduced. In brain, metabolic stress-elicited astrogliosis and microglia activation in the vicinity of plaques was also diminished by Astragalus membranaceus-polysaccharides administration. The plaque deposition, however, was not significantly affected by Astragalus membranaceus-polysaccharides administration. These findings suggest that Astragalus membranaceus-polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.

  7. Sulforaphane Ameliorates Bladder Dysfunction through Activation of the Nrf2-ARE Pathway in a Rat Model of Partial Bladder Outlet Obstruction

    Directory of Open Access Journals (Sweden)

    Chong Liu

    2016-01-01

    Full Text Available Purpose. We evaluated the effect of sulforaphane (SFN treatment on the function and changes of expression of Nrf2-ARE pathway in the bladder of rats with bladder outlet obstruction (BOO. Materials and Methods. A total of 18 male Sprague-Dawley rats at age of 8 weeks were divided into 3 groups (6 of each: the sham operated group, the BOO group, and the BOO+SFN group. We examined histological alterations and the changes of oxidative stress markers and the protein expression of the Nrf2-ARE pathway. Results. We found that SFN treatment could prolong micturition interval and increase bladder capacity and bladder compliance. However, the peak voiding pressure was lower than BOO group. SFN treatment can ameliorate the increase of collagen fibers induced by obstruction. SFN treatment also increased the activity of SOD, GSH-Px, and CAT compared to the other groups. The level of bladder cell apoptosis was decreased in BOO rats with SFN treatment. Moreover, SFN could reduce the ratio of Bax/Bcl-2 expression. Furthermore, SFN could activate the Nrf2 expression with elevation of its target antioxidant proteins. Conclusions. The sulforaphane-mediated decrease of oxidative stress and activation of the Nrf2-ARE pathway may ameliorate bladder dysfunction caused by bladder outlet obstruction.

  8. Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Jan Šilhavý

    Full Text Available Inflammation and oxidative stress have been implicated in the pathogenesis of metabolic disturbances. Esters of fumaric acid, mainly dimethyl fumarate, exhibit immunomodulatory, anti-inflammatory, and anti-oxidative effects. In the current study, we tested the hypothesis that fumaric acid ester (FAE treatment of an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP, will ameliorate inflammation, oxidative stress, and metabolic disturbances. We studied the effects of FAE treatment by administering Fumaderm, 10 mg/kg body weight for 4 weeks, to male SHR-CRP. Untreated male SHR-CRP rats were used as controls. All rats were fed a high sucrose diet. Compared to untreated controls, rats treated with FAE showed significantly lower levels of endogenous CRP but not transgenic human CRP, and amelioration of inflammation (reduced levels of serum IL6 and TNFα and oxidative stress (reduced levels of lipoperoxidation products in liver, heart, kidney, and plasma. FAE treatment was also