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  1. Adult neurogenesis is reduced in the dorsal hippocampus of rats displaying learned helplessness behavior.

    Science.gov (United States)

    Ho, Y C; Wang, S

    2010-11-24

    Clinical and preclinical studies suggest that the hippocampus has a role in the pathophysiology of major depression. In the learned helplessness (LH) animal model of depression after inescapable shocks (ISs) animals that display LH behavior have reduced cell proliferation in the hippocampus; this effect can be reversed by antidepressant treatment. Using this model, we compared rats that displayed LH behavior and rats that did not show LH behavior (NoLH) after ISs to determine whether reduced hippocampal cell proliferation is associated with the manifestation of LH behavior or is a general response to stress. Specifically, we examined cell proliferation, neurogenesis, and synaptic function in dorsal and ventral hippocampus of LH and NoLH animals and control rats that were not shocked. The LH rats had showed reduced cell proliferation, neurogenesis, and synaptic transmission in the dorsal hippocampus, whereas no changes were seen in the ventral hippocampus. These changes were not observed in the NoLH animals. In a group of NoLH rats that received the same amount of electrical shock as the LH rats to control for the unequal shocks received in these two groups, we observed changes in Ki-67(+) cells associated with acute stress. We conclude that reduced hippocampal cell proliferation and neurogenesis are associated with the manifestation of LH behavior and that the dorsal hippocampus is the most affected area. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome

    DEFF Research Database (Denmark)

    Buhl, Esben Selmer; Jessen, Niels; Pold, Rasmus

    2002-01-01

    , upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat. Furthermore, acute AICAR exposure has been found to reduce sterol and fatty acid synthesis in rat hepatocytes incubated in vitro as well as suppress endogenous glucose production in rats under euglycemic......-treated animals exhibited a tendency toward decreased intra-abdominal fat content. Furthermore, AICAR administration normalized the oral glucose tolerance test and decreased fasting concentrations of glucose and insulin close to the level of the lean animals. Finally, in line with previous findings, AICAR...... treatment was also found to enhance GLUT4 protein expression and to increase maximally insulin-stimulated glucose transport in primarily white fast-twitch muscles. Our data provide strong evidence that long-term administration of AICAR improves glucose tolerance, improves the lipid profile, and reduces...

  3. Prosocial Choice in Rats Depends on Food-Seeking Behavior Displayed by Recipients.

    Science.gov (United States)

    Márquez, Cristina; Rennie, Scott M; Costa, Diana F; Moita, Marta A

    2015-06-29

    Animals often are prosocial, displaying behaviors that result in a benefit to one another [1-15] even in the absence of self-benefit [16-21] (but see [22-25]). Several factors have been proposed to modulate these behaviors, namely familiarity [6, 13, 18, 20] or display of seeking behavior [16, 21]. Rats have been recently shown to be prosocial under distress [17, 18] (but see [26-29]); however, what drives prosociality in these animals remains unclear. To address this issue, we developed a two-choice task in which prosocial behavior did not yield a benefit or a cost to the focal rat. We used a double T-maze in which only the focal rat controlled access to the food-baited arms of its own and the recipient rat's maze. In this task, the focal rat could choose between one side of the maze, which yielded food only to itself (selfish choice), and the opposite side, which yielded food to itself and the recipient rat (prosocial choice). Rats showed a high proportion of prosocial choices. By manipulating reward delivery to the recipient and its ability to display a preference for the baited arm, we found that the display of food-seeking behavior leading to reward was necessary to drive prosocial choices. In addition, we found that there was more social investigation between rats in selfish trials than in prosocial trials, which may have influenced the focals' choices. This study shows that rats provide access to food to others in the absence of added direct self-benefit, bringing new insights into the factors that drive prosociality. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Reduce blurring and distortion in a projection type virtual image display using integrated small optics

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    Hasegawa, Tatsuya; Yendo, Tomohiro

    2015-03-01

    Head Up Display (HUD) is being applied to automobile. HUD displays information as far virtual image on the windshield. Existing HUD usually displays planar information. If the image corresponding to scenery on the road like Augmented Reality (AR) is displayed on the HUD, driver can efficiently get the information. To actualize this, HUD covering large viewing field is needed. However existing HUD cannot cover large viewing field. Therefore we have proposed system consisting of projector and many small diameter convex lenses. However observed virtual image has blurring and distortion . In this paper, we propose two methods to reduce blurring and distortion of images. First, to reduce blurring of images, distance between each of screen and lens comprised in lens array is adjusted. We inferred from the more distant the lens from center of the array is more blurred that the cause of blurring is curvature of field of lens in the array. Second, to avoid distortion of images, each lens in the array is curved spherically. We inferred from the more distant the lens from center of the array is more distorted that the cause of distortion is incident angle of ray. We confirmed effectiveness of both methods.

  5. Instrument-mounted displays for reducing cognitive load during surgical navigation.

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    Herrlich, Marc; Tavakol, Parnian; Black, David; Wenig, Dirk; Rieder, Christian; Malaka, Rainer; Kikinis, Ron

    2017-09-01

    Surgical navigation systems rely on a monitor placed in the operating room to relay information. Optimal monitor placement can be challenging in crowded rooms, and it is often not possible to place the monitor directly beside the situs. The operator must split attention between the navigation system and the situs. We present an approach for needle-based interventions to provide navigational feedback directly on the instrument and close to the situs by mounting a small display onto the needle. By mounting a small and lightweight smartwatch display directly onto the instrument, we are able to provide navigational guidance close to the situs and directly in the operator's field of view, thereby reducing the need to switch the focus of view between the situs and the navigation system. We devise a specific variant of the established crosshair metaphor suitable for the very limited screen space. We conduct an empirical user study comparing our approach to using a monitor and a combination of both. Results from the empirical user study show significant benefits for cognitive load, user preference, and general usability for the instrument-mounted display, while achieving the same level of performance in terms of time and accuracy compared to using a monitor. We successfully demonstrate the feasibility of our approach and potential benefits. With ongoing technological advancements, instrument-mounted displays might complement standard monitor setups for surgical navigation in order to lower cognitive demands and for improved usability of such systems.

  6. Displays mounted on cutting blocks reduce the learning curve in navigated total knee arthroplasty.

    Science.gov (United States)

    Schnurr, Christoph; Eysel, Peer; König, Dietmar Pierre

    2011-01-01

    The use of computer navigation in total knee arthroplasty (TKA) improves the implant alignment but increases the operation time. Studies have shown that the operation time is further prolonged due to the surgeon's learning curve, and longer operation times have been associated with higher morbidity risks. It has been our hypothesis that an improvement in the human-machine interface might reduce the time required during the learning curve. Accordingly, we asked whether the use of navigation devices with a display fixed on the surgical instruments would reduce the operation time in navigated TKAs performed by navigation beginners. Thirty medical students were randomized and used two navigation devices in rotation: these were the Kolibri® device with an external display and the Dash® device with a display that was fixed on the cutting blocks. The time for adjustment of the tibial and femoral cutting blocks on knee models while using these devices was measured. A significant time reduction was demonstration when the Dash® device was used: The time reduction was 21% for the tibial block (p = 0.007), 40% for the femoral block (p learning curve may be diminished.

  7. Unsaturated Fatty Acids Supplementation Reduces Blood Lead Level in Rats

    Science.gov (United States)

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: “super lecithin” (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

  8. Social instability stress in adolescent male rats reduces social interaction and social recognition performance and increases oxytocin receptor binding.

    Science.gov (United States)

    Hodges, Travis E; Baumbach, Jennet L; Marcolin, Marina L; Bredewold, Remco; Veenema, Alexa H; McCormick, Cheryl M

    2017-09-17

    Social experiences in adolescence are essential for displaying context-appropriate social behaviors in adulthood. We previously found that adult male rats that underwent social instability stress (SS) in adolescence had reduced social interactions with unfamiliar peers compared with non-stressed controls (CTL). Here we determined whether SS altered social recognition and social reward and brain oxytocin and vasopressin receptor density in adolescence. We confirmed that SS rats spent less time interacting with unfamiliar peers than did CTL rats (p=0.006). Furthermore, CTL rats showed a preference for novel over familiar conspecifics in a social recognition test whereas SS rats did not, which may reflect reduced recognition, impaired memory, or reduced preference for novelty in SS rats. The reward value of social interactions was not affected by SS based on conditioned place preference tests and based on the greater time SS rats spent investigating stimulus rats than did CTL rats when the stimulus rat was behind wire mesh (p=0.03). Finally, oxytocin receptor binding density was higher in the dorsal lateral septum and nucleus accumbens shell in SS rats compared with CTL rats (p=0.02, p=0.01, respectively). No effect of SS was found for vasopressin 1a receptor binding density in any of the brain regions analyzed. We discuss the extent to which the differences in social behavior exhibited after social instability in adolescence involve changes in social salience and social competency, and the possibility that changes in oxytocin signaling in the brain underlie the differences in social behavior. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Red maca (Lepidium meyenii reduced prostate size in rats

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    Rubio Julio

    2005-01-01

    Full Text Available Abstract Background Epidemiological studies have found that consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer. This effect seems to be due to aromatic glucosinolate content. Glucosinolates are known for have both antiproliferative and proapoptotic actions. Maca is a cruciferous cultivated in the highlands of Peru. The absolute content of glucosinolates in Maca hypocotyls is relatively higher than that reported in other cruciferous crops. Therefore, Maca may have proapoptotic and anti-proliferative effects in the prostate. Methods Male rats treated with or without aqueous extracts of three ecotypes of Maca (Yellow, Black and Red were analyzed to determine the effect on ventral prostate weight, epithelial height and duct luminal area. Effects on serum testosterone (T and estradiol (E2 levels were also assessed. Besides, the effect of Red Maca on prostate was analyzed in rats treated with testosterone enanthate (TE. Results Red Maca but neither Yellow nor Black Maca reduced significantly ventral prostate size in rats. Serum T or E2 levels were not affected by any of the ecotypes of Maca assessed. Red Maca also prevented the prostate weight increase induced by TE treatment. Red Maca administered for 42 days reduced ventral prostatic epithelial height. TE increased ventral prostatic epithelial height and duct luminal area. These increases by TE were reduced after treatment with Red Maca for 42 days. Histology pictures in rats treated with Red Maca plus TE were similar to controls. Phytochemical screening showed that aqueous extract of Red Maca has alkaloids, steroids, tannins, saponins, and cardiotonic glycosides. The IR spectra of the three ecotypes of Maca in 3800-650 cm (-1 region had 7 peaks representing 7 functional chemical groups. Highest peak values were observed for Red Maca, intermediate values for Yellow Maca and low values for Black Maca. These functional groups correspond among others to benzyl

  10. Sildenafil reduces polyuria in rats with lithium-induced NDI.

    Science.gov (United States)

    Sanches, Talita Rojas; Volpini, Rildo Aparecido; Massola Shimizu, Maria H; Bragança, Ana Carolina de; Oshiro-Monreal, Fabíola; Seguro, Antonio Carlos; Andrade, Lúcia

    2012-01-01

    Lithium (Li)-treated patients often develop urinary concentrating defect and polyuria, a condition known as nephrogenic diabetes insipidus (NDI). In a rat model of Li-induced NDI, we studied the effect that sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, has on renal expression of aquaporin-2 (AQP2), urea transporter UT-A1, Na(+)/H(+) exchanger 3 (NHE3), Na(+)-K(+)-2Cl(-) cotransporter (NKCC2), epithelial Na channel (ENaC; α-, β-, and γ-subunits), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase. We also evaluated cGMP levels in medullary collecting duct cells in suspension. For 4 wk, Wistar rats received Li (40 mmol/kg food) or no treatment (control), some receiving, in weeks 2-4, Sil (200 mg/kg food) or Li and Sil (Li+Sil). In Li+Sil rats, urine output and free water clearance were markedly lower, whereas urinary osmolality was higher, than in Li rats. The cGMP levels in the suspensions of medullary collecting duct cells were markedly higher in the Li+Sil and Sil groups than in the control and Li groups. Semiquantitative immunoblotting revealed the following: in Li+Sil rats, AQP2 expression was partially normalized, whereas that of UT-A1, γ-ENaC, and eNOS was completely normalized; and expression of NKCC2 and NHE3 was significantly higher in Li rats than in controls. Inulin clearance was normal in all groups. Mean arterial pressure and plasma arginine vasopressin did not differ among the groups. Sil completely reversed the Li-induced increase in renal vascular resistance. We conclude that, in experimental Li-induced NDI, Sil reduces polyuria, increases urinary osmolality, and decreases free water clearance via upregulation of renal AQP2 and UT-A1.

  11. 30.2 Digital PWM-driven AMOLED display on flex reducing static power consumption

    NARCIS (Netherlands)

    Genoe, J.; Obata, K.; Ameys, M.; Myny, K.; Ke, T.H.; Nag, M.; Steudel, S.; Schols, S.; Maas, J.; Tripathi, A.; Van Der Steen, J.-L.; Ellis, T.; Gelinck, G.H.; Heremans, P.

    2014-01-01

    The efficiency of small-molecule OLED devices increased substantially in recent years, creating opportunities for power-efficient displays, as only light is generated proportional to the subpixel intensity. However, current active matrix OLED (AMOLED) displays on foil do not validate this

  12. A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats

    Directory of Open Access Journals (Sweden)

    Vegard Lysne

    2015-06-01

    Full Text Available The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP, with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP.

  13. Exposure to Mozart music reduces cognitive impairment in pilocarpine-induced status epilepticus rats.

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    Xing, Yingshou; Qin, Yi; Jing, Wei; Zhang, Yunxiang; Wang, Yanran; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2016-02-01

    Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients.

  14. Reducing Peripheral Inflammation with Infliximab Reduces Neuroinflammation and Improves Cognition in Rats with Hepatic Encephalopathy

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    Dadsetan, Sherry; Balzano, Tiziano; Forteza, Jerónimo; Cabrera-Pastor, Andrea; Taoro-Gonzalez, Lucas; Hernandez-Rabaza, Vicente; Gil-Perotín, Sara; Cubas-Núñez, Laura; García-Verdugo, José-Manuel; Agusti, Ana; Llansola, Marta; Felipo, Vicente

    2016-01-01

    Inflammation contributes to cognitive impairment in patients with hepatic encephalopathy (HE). However, the process by which peripheral inflammation results in cognitive impairment remains unclear. In animal models, neuroinflammation and altered neurotransmission mediate cognitive impairment. Taking into account these data, we hypothesized that in rats with HE: (1) peripheral inflammation is a main contributor to neuroinflammation; (2) neuroinflammation in hippocampus impairs spatial learning by altering AMPA and/or NMDA receptors membrane expression; (3) reducing peripheral inflammation with infliximab (anti-TNF-a) would improve spatial learning; (4) this would be associated with reduced neuroinflammation and normalization of the membrane expression of glutamate receptors. The aims of this work were to assess these hypotheses. We analyzed in rats with portacaval shunt (PCS) and control rats, treated or not with infliximab: (a) peripheral inflammation by measuring prostaglandin E2, IL10, IL-17, and IL-6; (b) neuroinflammation in hippocampus by analyzing microglial activation and the content of TNF-a and IL-1b; (c) AMPA and NMDA receptors membrane expression in hippocampus; and (d) spatial learning in the Radial and Morris water mazes. We assessed the effects of treatment with infliximab on peripheral inflammation, on neuroinflammation and AMPA and NMDA receptors membrane expression in hippocampus and on spatial learning and memory. PCS rats show increased serum prostaglandin E2, IL-17, and IL-6 and reduced IL-10 levels, indicating increased peripheral inflammation. PCS rats also show microglial activation and increased nuclear NF-kB and expression of TNF-a and IL-1b in hippocampus. This was associated with altered AMPA and NMDA receptors membrane expression in hippocampus and impaired spatial learning and memory in the radial and Morris water maze. Treatment with infliximab reduces peripheral inflammation in PCS rats, normalizing prostaglandin E2, IL-17, IL-6, and

  15. Shenfu injection reduces toxicity of bupivacaine in rats

    Institute of Scientific and Technical Information of China (English)

    王强; 刘艳红; 雷毅; 杨静; 陈绍洋; 陈敏; 熊利泽

    2003-01-01

    Objective To investigate the effects of injecting Shenfu, an extract of traditional Chinese herbal medicines, on the central nervous system (CNS) and the cardiac toxicity of bupivacaine in rats. Methods Sixteen male Sprague-Dawley rats, weighing form 280 to 320 g, were randomly assigned to two groups (n=8 in each group). Animals in the control group received a saline injection 10 ml/kg while animals in the Shenfu group received an injection of Shenfu 10 ml/kg intraperitoneally 30 minutes before intravenous infusion of bupivacaine. Lead Ⅱ of an electrocardiogram (EEG) was continuously monitored after 3 needles were inserted into the skin of both forelimbs and the left hind-leg of each rat. The femoral artery was cannulated for measurement of arterial blood pressure and blood sampling. The femoral vein was cannulated for the infusion of bupivacaine. After baseline measurement (arterial blood pressure, heart rate and arterial blood gas), 0.5% bupivacaine was infused intravenously at a rate of 2 mg*kg-1*min-1 to all animals until asystole occurred. The time of bupivacaine-induced convulsions, arrhythmia and asystole were determined. The dose of bupivacaine was then calculated at the corresponding time point. Results The doses of bupivacaine that induced convulsions, arrhythmia and cardiac arrest were remarkably larger in Shenfu injection-treated animals than in saline-treated rats [convulsions, (10.5±1.9) mg/kg vs (7.2±1.5) mg/kg; arrhythmia (10.5±2.0) mg/kg vs (7.2±1.9) mg/kg; asystole, (32.8±8.5) mg/kg vs (25.0±5.0) mg/kg; P=0.006, 0.009 and 0.044, respectively]. Conclusion The Shenfu injection is able to reduce the toxicity of bupiralaine to CNS and cardiac system in rats.

  16. Exercise reduces inflammation and cell proliferation in rat colon carcinogenesis.

    Science.gov (United States)

    Demarzo, Marcelo Marcos Piva; Martins, Lisandra Vanessa; Fernandes, Cleverson Rodrigues; Herrero, Fábio Augusto; Perez, Sérgio Eduardo de Andrade; Turatti, Aline; Garcia, Sérgio Britto

    2008-04-01

    There is evidence that the risk of colon cancer is reduced by appropriate levels of physical exercise. Nevertheless, the mechanisms involved in this protective effect of exercise remain largely unknown. Inflammation is emerging as a unifying link between a range of environment exposures and neoplastic risk. The carcinogen dimethyl-hydrazine (DMH) induces an increase in epithelial cell proliferation and in the expression of the inflammation-related enzyme cyclooxigenase-2 (COX-2) in the colon of rats. Our aim was to verify whether these events could be attenuated by exercise. Four groups of eight Wistar rats were used in the experiment. The groups G1 and G3 were sedentary (controls), and the groups G2 and G4 were submitted to 8 wk of swimming training, 5 d.wk. The groups G3 and G4 were given subcutaneous injections of DMH immediately after the exercise protocols. Fifteen days after the neoplasic induction, the rats were sacrificed and the colon was processed for histological examination and immunohistochemistry staining of proliferating cell nuclear antigen (PCNA) and COX-2. We found a significant increase in the PCNA-labeling index in both DMH-treated groups of rats. However, this increase was significantly attenuated in the training group G4 (P < 0.01). Similar results were observed in relation to the COX-2 expression. From our findings, we conclude that exercise training exerts remarkable antiproliferative and antiinflammatory effects in the rat colonic mucosa, suggesting that this may be an important mechanism to explain how exercise protects against colonic cancer.

  17. Fermented Citrus Lemon Reduces Liver Injury Induced by Carbon Tetrachloride in Rats

    Directory of Open Access Journals (Sweden)

    Yi Jinn Lillian Chen

    2018-01-01

    Full Text Available Fermented lemon juice displays a variety of important biological activities, including anti-inflammatory and antioxidant capabilities. The aim of the present study is to investigate hepatic-protective effects of no-sugar-added fermented lemon juice (FLJ for liver inflammation caused by carbon tetrachloride (CCl4 in rats. Rats are divided into six groups: H2O, CCl4 + H2O, CCl4 + silymarin, and CCl4 plus three different FLJ doses by oral administration, respectively. The results show that the contents of plasma ALT and AST, hepatic lipid peroxidation, splenomegaly, and liver water are reduced significantly in rats under FLJ treatment, and pathological examination of liver fibrosis is improved. The reduced hepatic injury by increasing liver soluble protein and glutathione and albumin is observed in FLJ treated groups, and FLJ has comparable efficacies to medicine silymarin in liver therapies. The no-sugar-added FLJ differs from traditional fermentation by adding lots of sugar and prevents any hidden sugar intake while taking it as a complimentary treatment for liver inflammation. The green color and the taste of sourness are both associated with treating and healing the liver based on the five-element theory in traditional Chinese medicine, and the green and sour FLJ may be applied to the ancient theory in preventing hepatic injury accordingly.

  18. Lifelong Aerobic Exercise Reduces the Stress Response in Rats.

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    Pietrelli, A; Di Nardo, M; Masucci, A; Brusco, A; Basso, N; Matkovic, L

    2018-04-15

    The aim of this study was to analyze the effects of lifelong aerobic exercise (AE) on the adaptive response of the stress system in rats. It is well known that hypothalamic-pituitary-adrenal axis (HPA) activity differs when triggered by voluntary or forced exercise models. Male Wistar rats belonging to exercise (E) or control (C) groups were subjected to chronic AE, and two cutoff points were established at 8 (middle age) and 18 months (old age). Behavioral, biochemical and histopathological studies were performed on the main components/targets of the stress system. AE increased adrenal sensitivity (AS), brain corticosterone (CORT) and corticotropin-releasing factor (CRF), but had no effect on the thymus, adrenal glands (AGs) weight or plasma CORT. In addition, AE exerted no effect on the sympathetic tone, but significantly reduced anxiety-related behavior and emotionality. Aging decreased AS and deregulated neuroendocrine feedback, leading to an anxiogenic state which was mitigated by AE. Histopathological and morphometric analysis of AGs showed no alterations in middle-aged rats but adrenal vacuolization in approximately 20% old rats. In conclusion, lifelong AE did not produce adverse effects related to a chronic stress state. On the contrary, while AE upregulated some components of the HPA axis, it generated an adaptive response to cumulative changes, possibly through different compensatory and/or super compensatory mechanisms, modulated by age. The long-term practice of AE had a strong positive impact on stress resilience so that it could be recommended as a complementary therapy in stress and depression disease. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Perceived Intensity of Emotional Point-Light Displays Is Reduced in Subjects with ASD

    Science.gov (United States)

    Krüger, Britta; Kaletsch, Morten; Pilgramm, Sebastian; Schwippert, Sven-Sören; Hennig, Jürgen; Stark, Rudolf; Lis, Stefanie; Gallhofer, Bernd; Sammer, Gebhard; Zentgraf, Karen; Munzert, Jörn

    2018-01-01

    One major characteristic of autism spectrum disorder (ASD) is problems with social interaction and communication. The present study explored ASD-related alterations in perceiving emotions expressed via body movements. 16 participants with ASD and 16 healthy controls observed video scenes of human interactions conveyed by point-light displays. They…

  20. Jinlida reduces insulin resistance and ameliorates liver oxidative stress in high-fat fed rats.

    Science.gov (United States)

    Liu, Yixuan; Song, An; Zang, Shasha; Wang, Chao; Song, Guangyao; Li, Xiaoling; Zhu, Yajun; Yu, Xian; Li, Ling; Wang, Yun; Duan, Liyuan

    2015-03-13

    Jinlida (JLD) is a compound preparation formulated on the basis of traditional Chinese medicine and is officially approved for the treatment of type 2 diabetes (T2DM) in China. We aimed to elucidate the mechanism of JLD treatment, in comparison to metformin treatment, on ameliorating insulin sensitivity in insulin resistant rats and to reveal its anti-oxidant properties. Rats were fed with standard or high-fat diet for 6 weeks. After 6 weeks, the high-fat fed rats were subdivided into five groups and orally fed with JLD or metformin for 8 weeks. Fasting blood glucose (FBG), fasting blood insulin, blood lipid and antioxidant enzymes were measured. Intraperitoneal glucose tolerance test (IPGTT) and hyperinsulinemic euglycemic clamp technique were carried out to measure insulin sensitivity. Gene expression of the major signaling pathway molecules that regulate glucose uptake, including insulin receptor (INSR), insulin receptor substrate-1 (IRS-1), phosphoinositide-3-kinase (PI3K), protein kinase beta (AKT), and glucose transporter type 2 (GLUT2), were assessed by quantitative RT-PCR. The totle and phosphorylation expression of IRS-1, AKT, JNK and p38MAPK were determined by Western blot. Treatment with JLD effectively ameliorated the high-fat induced hyperglycemia, hyperinsulinemia and hyperlipidemia. Similar to metformin, the high insulin resistance in high-fat fed rats was significantly decreased by JLD treatment. JLD displayed anti-oxidant effects, coupled with up-regulation of the insulin signaling pathway. The attenuation of hepatic oxidative stress by JLD treatment was associated with reduced phosphorylation protein levels of JNK and p38MAPK. Treatment with JLD could moderate glucose and lipid metabolism as well as reduce hepatic oxidative stress, most likely through the JNK and p38MAPK pathways. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Infusions of muscimol into the lateral septum do not reduce rats' defensive behaviors toward a cat odor stimulus.

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    Chee, San-San A; Patel, Ronak; Menard, Janet L

    2015-01-01

    The lateral septum (LS) is implicated in behavioral defense. We tested whether bilateral infusions of the GABAA receptor agonist muscimol into the LS suppress rats' defensive responses to cat odor. Rats received intra-LS infusions of either saline or muscimol (40 ng/rat) and were exposed to either a piece of a cat collar that had been previously worn by a cat or to a control (cat odor free) collar. Rats exposed to the cat odor collar displayed more head-out postures, while intra-LS application of muscimol reduced the number of head-out postures. However, this reduction was also present in rats exposed to a control (cat odor free) collar. This latter finding suggests that despite its involvement in other defensive behaviors (e.g., open arm avoidance in the elevated plus maze), the LS does not selectively regulate rats' receptor defensive responding to the olfactory cues present in our cat odor stimulus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Ulinastatin Reduces T Cell Apoptosis in Rats with Severe Acute ...

    African Journals Online (AJOL)

    in rats with severe acute pancreatitis (SAP) and to elucidate its underlying molecular mechanism. Methods: Thirty .... on T lymphocytes apoptosis in SAP rat model and elucidated ..... oxygen radicals, the exhaustion of adenine nucleotide and ...

  3. Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats.

    Science.gov (United States)

    Meng, Li; Rijntjes, Eddy; Swarts, Hans J M; Keijer, Jaap; Teerds, Katja J

    2017-03-16

    There is substantial evidence both in humans and in animals that a prolonged reduction in plasma thyroid hormone concentration leads to reproductive problems, including disturbed folliculogenesis, impaired ovulation and fertilization rates, miscarriage and pregnancy complications. The objective of the present study is to examine the consequences of chronic hypothyroidism, induced in adulthood, for the size of the ovarian follicle pool. In order to investigate this, adult female rats were provided either a control or an iodide deficient diet in combination with perchlorate supplementation to inhibit iodide uptake by the thyroid. Sixteen weeks later animals were sacrificed. Blood was collected for hormone analyses and ovaries were evaluated histologically. At the time of sacrifice, plasma thyroid-stimulating hormone concentrations were 20- to 40-fold increased, thyroxine concentrations were negligible while tri-iothyronin concentrations were decreased by 40% in the hypothyroid group, confirming that the animals were hypothyroid. Primordial, primary and preantral follicle numbers were significantly lower in the hypothyroid ovaries compared to the euthyroid controls, while a downward trend in antral follicle and corpora lutea numbers was observed. Surprisingly the percentage of atretic follicles was not significantly different between the two groups, suggesting that the reduced preantral and antral follicle numbers were presumably not the consequence of increased degeneration of these follicle types in the hypothyroid group. Plasma anti-Müllerian hormone (AMH) levels showed a significant correlation with the growing follicle population represented by the total ovarian number of primary, preantral and antral follicles, suggesting that also under hypothyroid conditions AMH can serve as a surrogate marker to assess the growing ovarian follicle population. The induction of a chronic hypothyroid condition in adult female rats negatively affects the ovarian follicular

  4. Histomorphologic change of radiation pneumonitis in rat lungs: captopril reduces rat lung injury induced by irradiation

    International Nuclear Information System (INIS)

    Kim, Jin Hee

    1999-01-01

    To assess the histomorphologic changes in the rat lung injury induced by radiation, to determine whether captopril reduces the rat lung injury and to evaluate change in TNF-α and TGF β and rat lung damage by radiation and captopril. Right lungs in male Sprague-Dawley rats were divided irradiation alone (10, 20, 30 Gy) or radiation (same dose with radiation alone group) with captopril (500 mg/L). Radiation alone group were sacrificed at twelve hours and eleven weeks after radiation and radiation with captopril group (captopril group) were sacrificed at eleven weeks after radiation with captopril. We examined the light microscope and electron microscopic features in the groups. In radiation alone group, there were patch parenchymal collapse and consolidation at twelve hours after radiation. The increase of radiation dose shows more prominent the severity and broader the affected areas. Eleven weeks after radiation, the severity and areas of fibrosis had increased in proportion to radiation dose given in the radiation alone group. There was notable decrease of lung fibrosis in captopril group than in radiation alone group. The number of mast cells rapidly increased with increase of radiation dose in radiation alone group and the degree of increase of mast cell number and severity of collagen accumulation more decreased in captopril group than in radiation alone group. In radiation alone group expression of TNF-α and TGF-β] increased according to increase of radiation dose at twelve hours after radiation in both group. At eleven weeks after radiation, expression of TGF- P increased according to increase of radiation dose in radiation group but somewhat decreased in captopril group. In the captopril group the collagen deposition increased but less dense than those of radiation alone group. The severity of perivascular thickening, capillary change, the number and degranulation of mast cells more decreased in the captopril group than in the radiation alone group. It

  5. Reducing pulmonary injury by hyperbaric oxygen preconditioning during simulated high altitude exposure in rats.

    Science.gov (United States)

    Li, Zhuo; Gao, Chunjin; Wang, Yanxue; Liu, Fujia; Ma, Linlin; Deng, Changlei; Niu, Ko-Chi; Lin, Mao-Tsun; Wang, Chen

    2011-09-01

    Hyperbaric oxygen preconditioning (HBO₂P + HAE) has been found to be beneficial in preventing the occurrence of ischemic damage to brain, spinal cord, heart, and liver in several disease models. In addition, pulmonary inflammation and edema are associated with a marked reduction in the expression levels of both aquaporin (AQP) 1 and AQP5 in the lung. Here, the aims of this study are first to ascertain whether acute lung injury can be induced by simulated high altitude in rats and second to assess whether HBO2P + HAE is able to prevent the occurrence of the proposed high altitude-induced ALI. Rats were randomly divided into the following three groups: the normobaric air (NBA; 21% O₂ at 1 ATA) group, the HBO₂P + high altitude exposure (HAE) group, and the NBA + HAE group. In HBO₂P + HAE group, animals received 100% O₂ at 2.0 ATA for 1 hour per day, for five consecutive days. In HAE groups, animals were exposed to a simulated HAE of 6,000 m in a hypobaric chamber for 24 hours. Right after being taken out to the ambient, animals were anesthetized generally and killed and thoroughly exsanguinated before their lungs were excised en bloc. The lungs were used for both histologic and molecular evaluation and analysis. In NBA + HAE group, the animals displayed higher scores of alveolar edema, neutrophil infiltration, and hemorrhage compared with those of NBA controls. In contrast, the levels of both AQP1 and AQP5 proteins and mRNA expression in the lung in the NBA + HAE group were significantly lower than those of NBA controls. However, the increased lung injury scores and the decreased levels of both AQP1 and AQP5 proteins and mRNA expression in the lung caused by HAE was significantly reduced by HBO₂P + HAE. Our results suggest that high altitude pulmonary injury may be prevented by HBO2P + HAE in rats.

  6. Solanum paniculatum root extract reduces diarrhea in rats

    Directory of Open Access Journals (Sweden)

    Jonh A.B. Tenório

    Full Text Available Abstract Solanum paniculatum L., Solanaceae, locally known as "jurubeba", is widely used in Brazil for culinary purposes, and in folk medicine to treat of diverse disorder including gastric dysfunctions. In this study we investigated the antidiarrheal activity of S. paniculatum roots extract in rats at different concentrations (125, 250 and 500 mg/kg, p.o using different experimental models such as castor oil-induced diarrhea, enteropooling and gastrointestinal motility, determined by in vivo experimental models. The major compound of root extract was characterized as chlorogenic acid based in the IR, 1D and 2D NMR analysis. All the extract doses achieved antidiarrheal potency, as indicated by reduced weight of feces in castor oil-induced diarrhea, decreased intestinal motility and significantly inhibited castor oil-induced enteropooling compared to the vehicle group. The highest dose (500 mg/kg produced greater anti-motility effect and better reduction of enteropooling, similar to the reference drug Loperamide (5 mg/kg. Extract from S. paniculatum L. roots had antidiarrheal activity, as shown by the lower weight of the feces as well as decrease in the accumulation of intestinal fluid and slower transit, justifying the traditional use of plant for diarrhea.

  7. Nonabsorbable Antibiotics Reduce Bacterial and Endotoxin Translocation in Hepatectomised Rats

    Directory of Open Access Journals (Sweden)

    S. K. Kakkos

    1997-01-01

    Full Text Available There is increasing evidence that septic complications, occurring after major hepatectomies, may be caused by gram negative bacteria, translocating from the gut. We investigated in rats, the effect of extended hepatectomy on the structure and morphology of the intestinal mucosa as well as on the translocation of intestinal bacteria and endotoxins. We also examined the effect of nonabsorbable antibiotics on reducing the intestinal flora and consequently the phenomenon of translocation by administering neomycin sulphate and cefazoline. Hepatectomy was found to increase translocation, while administration of nonabsorbable antibiotics decreased it significantly. In addition, hepatectomy increased the aerobic cecal bacterial population, which normalised in the group receiving antibiotics. Among the histological parameters evaluated, villus height demonstrated a significant reduction after hepatectomy, while the number of villi per cm and the number of mitoses per crypt, remained unchanged. Our results indicate that administration of nonabsorbable antibiotics presents a positive effect on bacterial and endotoxin translocation after extended hepatectomy, and this may be related to reduction of colonic bacterial load as an intraluminal effect of antibiotics.

  8. Patients in a vegetative state following traumatic brain injury display a reduced intracortical modulation.

    Science.gov (United States)

    Bagnato, Sergio; Boccagni, Cristina; Sant'Angelo, Antonino; Prestandrea, Caterina; Rizzo, Silvia; Galardi, Giuseppe

    2012-10-01

    Patients in coma who fail to wake develop a condition known as a vegetative state (VS). While we know that some cortical activities exist in patients in VS, it remains unclear whether interneuronal modulation can be abnormal in the cerebral cortex of these patients. The aim of the study was to evaluate the inhibitory and excitatory interneuronal circuits in patients in VS following a traumatic brain injury. Cortical excitability was studied in 5 VS patients and in 10 healthy subjects using paired pulses transcranial magnetic stimulation (TMS). Resting motor threshold and intracortical inhibition and facilitation at short intervals (2 and 10 ms, respectively) were evaluated. Two patients were studied again after their level of consciousness transitioned into a minimally conscious state (MCS). Both intracortical inhibition and facilitation were significantly reduced in patients compared to healthy subjects (p<0.05). In addition, these results did not significantly change in the 2 patients who evolved into a MCS. This is the first report showing an abnormal cortical excitability in patients in VS. Our findings suggest a pathophysiological base for future work aiming to restore the lack of interneuronal transmission in patients in VS. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Wall lizards display conspicuous signals to conspecifics and reduce detection by avian predators

    Science.gov (United States)

    Stevens, Martin

    2014-01-01

    Visual signals are often under conflicting selection to be hidden from predators while being conspicuous to mates and rivals. Here, we investigated whether 3 different island populations of Aegean wall lizards (Podarcis erhardii) with variable coloration among diverse island habitats exhibit simultaneous camouflage and sexual signals. We examined whether signals appear better tuned to conspecific vision as opposed to that of avian predators, and whether background-matching camouflage and sexual signals are partitioned to specific body regions. This could facilitate both covert sexual signaling and camouflage according to the viewing perspectives of predators and conspecifics. We found that lizards typically appeared twice as conspicuous to conspecifics than to avian predators against the same visual background, largely due to lizards’ enhanced sensitivity to ultraviolet, suggesting that P. erhardii signals are tuned to conspecific vision to reduce detection by predators. Males were more conspicuous than females to both predators and conspecifics. In 2 populations, male backs were relatively more camouflaged to predators compared to signaling flanks, whereas in females, exposed and concealed surfaces were camouflaged to predators and generally did not differ in background matching. These findings indicate that lizard coloration evolves under the competing demands of natural and sexual selection to promote signals that are visible to conspecifics while being less perceptible to avian predators. They also elucidate how interactions between natural and sexual selection influence signal detectability and partitioning to different body regions, highlighting the importance of considering receiver vision, viewing perspectives, and signaling environments in studies of signal evolution. PMID:25419083

  10. Investigating the procedural variables that determine whether rats will display negative anticipatory contrast or positive induction.

    Science.gov (United States)

    Weatherly, Jeffrey N; Nurnberger, Jeri T; Hanson, Brent C

    2005-08-31

    Previous studies have demonstrated that consumption of a low-valued food substance may decrease if access to a high-valued substance will soon be available (negative anticipatory contrast). Research has also demonstrated that responding for a low-valued reinforcer may increase if responding for a high-valued reinforcer will soon be possible (positive induction). The present experiment employed rats to respond in a procedure similar to that typically used to produce negative anticipatory contrast. The goal was to determine what factors contribute to when a contrast or an induction effect will occur. Based on previous research, the influence of auditory cues, temporal delays, food deprivation, and location of substance delivery were investigated. Auditory cues and temporal delays did little to influence whether subjects increased or decreased their consumption of 1% sucrose when access to 32% sucrose was upcoming. The appearance of contrast or induction was related to level of deprivation, with deprivation promoting induction. Which effect occurred also depended on whether subjects consumed the two substances from one spout in one location (induction) or from two different spouts in two different locations (contrast). The present results help identify the procedural link(s) between these two effects. They also provide insight to why positive induction may occur (i.e., higher-order place conditioning).

  11. Bexarotene reduces blood-brain barrier permeability in cerebral ischemia-reperfusion injured rats.

    Directory of Open Access Journals (Sweden)

    Lu Xu

    Full Text Available Matrix metalloproteinase-9 (MMP-9 over-expression disrupts the blood-brain barrier (BBB in the ischemic brain. The retinoid X receptor agonist bexarotene suppresses MMP-9 expression in endothelial cells and displays neuroprotective effects. Therefore, we hypothesized that bexarotene may have a beneficial effect on I/R-induced BBB dysfunction.A total of 180 rats were randomized into three groups (n = 60 each: (i a sham-operation group, (ii a cerebral ischemia-reperfusion (I/R group, and (iii an I/R+bexarotene group. Brain water content was measured by the dry wet weight method. BBB permeability was analyzed by Evans Blue staining and the magnetic resonance imaging contrast agent Omniscan. MMP-9 mRNA expression, protein expression, and activity were assessed by reverse transcription polymerase chain reaction, Western blotting, and gelatin zymography, respectively. Apolipoprotein E (apoE, claudin-5, and occludin expression were analyzed by Western blotting.After 24 h, 48 h, and 72 h post-I/R, several effects were observed with bexarotene administration: (i brain water content and BBB permeability were significantly reduced; (ii MMP-9 mRNA and protein expression as well as activity were significantly decreased; (iii claudin-5 and occludin expression were significantly increased; and (iv apoE expression was significantly increased.Bexarotene decreases BBB permeability in rats with cerebral I/R injury. This effect may be due in part to bexarotene's upregulation of apoE expression, which has been previously shown to reduce BBB permeability through suppressing MMP-9-mediated degradation of the tight junction proteins claudin-5 and occludin. This work offers insight to aid future development of therapeutic agents for cerebral I/R injury in human patients.

  12. Memory Retrieval before or after Extinction Reduces Recovery of Fear in Adolescent Rats

    Science.gov (United States)

    Baker, Kathryn D.; McNally, Gavan P.; Richardson, Rick

    2013-01-01

    Adolescent rats exhibit impaired extinction retention compared to pre-adolescent and adult rats. A single nonreinforced exposure to the conditioned stimulus (CS; a retrieval trial) given shortly before extinction has been shown in some circumstances to reduce the recovery of fear after extinction in adult animals. This study investigated whether a…

  13. Melatonin reduces dimethylnitrosamine-induced liver fibrosis in rats.

    Science.gov (United States)

    Tahan, Veysel; Ozaras, Resat; Canbakan, Billur; Uzun, Hafize; Aydin, Seval; Yildirim, Beytullah; Aytekin, Huseyin; Ozbay, Gulsen; Mert, Ali; Senturk, Hakan

    2004-09-01

    Increased deposition of the extracellular matrix components, particularly collagen, is a central phenomenon in liver fibrosis. Stellate cells, the central mediators in the pathogenesis of fibrosis are activated by free radicals, and synthesize collagen. Melatonin is a potent physiological scavenger of hydroxyl radicals. Melatonin has also been shown to be involved in the inhibitory regulation of collagen content in tissues. At present, no effective treatment of liver fibrosis is available for clinical use. We aimed to test the effects of melatonin on dimethylnitrosamine (DMN)-induced liver damage in rats. Wistar albino rats were injected with DMN intraperitoneally. Following a single dose of 40 mg/kg DMN, either saline (DMN) or 100 mg/kg daily melatonin was administered for 14 days. In other rats, physiologic saline or melatonin were injected for 14 days, following a single injection of saline as control. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) levels were evaluated in blood and tissue homogenates. DMN caused hepatic fibrotic changes, whereas melatonin suppressed these changes in five of 14 rats (P < 0.05). DMN administration resulted in increased hydroxyproline and MDA levels, and decreased GSH and SOD levels, whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice.

  14. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction.

    Science.gov (United States)

    Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

    2013-08-15

    From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

  15. Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats

    International Nuclear Information System (INIS)

    Winocour, P.D.; Colwell, J.A.

    1985-01-01

    Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, the authors used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. The authors conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis

  16. Metformin reduces intrahepatic fibrosis and intrapulmonary shunts in biliary cirrhotic rats

    Directory of Open Access Journals (Sweden)

    Mu-Tzu Ko

    2017-08-01

    Conclusion: Metformin reduced liver injury and improved hepatic fibrosis in cirrhotic rats. It also attenuated the intrapulmonary shunts. However, the effects of metformin on pulmonary angiogenesis and hypoxia were insignificant.

  17. Equisetum sylvaticum base reduces atherosclerosis risk factors in rats fed a high-fat diet

    Directory of Open Access Journals (Sweden)

    Cheng-He Lin

    2014-08-01

    Full Text Available We identify an Equisetum sylvaticum alkaloid (ESA derived from E. hyemale, which has robust antihyperlipidemic effects in rats fed a high-fat diet. ESA was isolated from E. hyemale and identified by IR, 13C NMR and 1H NMR. Rats were induced to hyperlipidemia and subjected to ESA treatment. In hyperlipidemic model, fed with a high-fat diet, the blood levels of TC, TG and LDL-C were increased. The administration of ESA (20 or 40 mg/kg to those rats significantly improved the HDL-C level and reduced the levels of TC, TG, LDL-C. The atherosclerosis index and atherosclerosis risk of these rats were significantly reduced by ESA. In addition, the administration of ESA in rats increased the activity of SOD and decreased the level of MDA. These results reveal the antihyperlipidemic and anti-oxidative effects of ESA in vivo.

  18. Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats

    DEFF Research Database (Denmark)

    Liaset, Bjørn; Madsen, Lise; Hao, Qin

    2009-01-01

    levels relative to rats fed soy protein or casein. Concomitantly, the saithe FPH fed rats had reduced liver lipids and fasting plasma TAG levels. Furthermore, visceral adipose tissue mass was reduced and expression of genes involved in fatty acid oxidation and energy expenditure was induced in perirenal....../retroperitoneal adipose tissues of rats fed saithe FPH. Our results provide the first evidence that dietary protein sources with different amino acid compositions can modulate the level of plasma bile acids and our data suggest potential novel mechanisms by which dietary protein sources can affect energy metabolism....

  19. Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by contralateral nerve root transfer.

    Science.gov (United States)

    Zong, Haiyang; Ma, Fenfen; Zhang, Laiyin; Lu, Huiping; Gong, Jingru; Cai, Min; Lin, Haodong; Zhu, Yizhun; Hou, Chunlin

    2016-12-01

    Lower extremity spasticity is a common sequela among patients with acquired brain injury. The optimum treatment remains controversial. The aim of our study was to test the feasibility and effectiveness of contralateral nerve root transfer in reducing post stroke spasticity of the affected hindlimb muscles in rats. In our study, we for the first time created a novel animal hindlimb spastic hemiplegia model in rats with photothrombotic lesion of unilateral motor cortex and we established a novel surgical procedure in reducing motor cortex lesion-induced hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three groups. In group A, rats received sham operation. In group B, rats underwent unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5 ventral root of the affected side. Footprint analysis, Hoffmann reflex (H-reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter 1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length recovered significantly in group C compared with group B (Pmotor cortex lesion-induced hindlimb spasticity in rats. Our data indicated that this could be an alternative treatment for unilateral lower extremity spasticity after brain injury. Therefore, contralateral neurotization may exert a potential therapeutic candidate to improve the function of lower extremity in patients with spastic hemiplegia. © 2016 The Author(s).

  20. Critically ill neonates displayed stable vital parameters and reduced metabolic acidosis during neonatal emergency airborne transport in Sweden.

    Science.gov (United States)

    Frid, Ingrid; Ågren, Johan; Kjellberg, Mattias; Normann, Erik; Sindelar, Richard

    2018-02-26

    This study evaluated the medical quality of acute airborne transports carried out by a neonatal emergency transport service in a Swedish healthcare region from 2012 to 2015. The transport charts and patient records of all infants transported to the regional centre were reviewed for transport indications and vital parameters and outcomes. We identified 187 acute airborne transports and the main indications for referral were therapeutic hypothermia after perinatal asphyxia, extremely preterm birth and respiratory failure. There were 37 deaths, but none of these occurred during transport and none of the deaths that occurred within 24 hours after transport were found to be related to the transport per se. No differences were found in vital parameters or ventilator settings before and after transport, except for an improvement in blood pH (7.22 ± 0.13 versus 7.27 ± 0.13, mean ± SD, p < 0.01), due to a decrease in base deficit (-8.0 ± 6.8 versus -5.4 ± 6.3 mmol, p < 0.001), while the partial pressure of carbon dioxide remained unchanged. During air transport, critically ill neonates displayed stable vital parameters and reduced metabolic acidosis. No transport-related mortality was found, but the high number of extremely preterm infants transported indicates the potential for improving in-utero transport. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  1. Reduced gluconeogenesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Gorski, J.R. (Kansas Univ., Kansas City, KS (USA). Dept. of Pharmacology, Toxicology and Therapeutics); Weber, L.W.D.; Rozman, K. (Kansas Univ., Kansas City, KS (USA). Dept. of Pharmacology, Toxicology and Therapeutics Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen (GSF), Neuherberg (Germany, F.R.). Inst. fuer Toxikologie)

    1990-01-01

    The effect of a usually lethal dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 125 {mu}g/kg) was studied on the conversion of {sup 14}C-alanine into {sup 14}C-glucose in male Sprague-Dawley rats by established procedures (determination of plasma alanine and blood glucose by enzymatic assays and isolation of {sup 14}C-alanine and {sup 14}C-glucose from whole blood by column chromatography). TCDD-treated rats converted significantly (p < 0.05) less {sup 14}C-alanine into {sup 14}C-glucose than did their pair-fed or ad libitum-fed counterparts, indicating reduced gluconeogenesis as a result of TCDD treatment. This finding suggests that reduced gluconeogenesis in TCDD-treated rats contributed to the progressively developing, severe hypoglycemia observed in these animals. Corticosterone, a key hormone in gluconeogenesis, provides partial protection from TCDD-induced toxicity in hypophysectomized rats. Therefore, the conversion of {sup 14}C-alanine into {sup 14}C-glucose was also determined in hypophysectomized rats dosed with TCDD (125 {mu}g/kg) and given corticosterone (25 {mu}g/ml in drinking water). These rats also converted significantly (p < 0.05) less {sup 14}C-alanine into {sup 14}C-glucose than did their pair-fed counterparts. However, in contrast to non-hypophysectomized TCDD-treated rats, these rats maintained marginal normoglycemia even at 64 days after dosing with TCDD, which suggests that the partial protective effect of corticosterone in hypophysectomized, TCDD-treated rats is unrelated to its efffect on gluconeogenesis. The protection provided by corticosterone supplementation in TCDD toxicity is more likely due to reduced peripheral utilization of glucose enabling the animals to maintain marginal normoglycemia. (orig.).

  2. Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia.

    Science.gov (United States)

    Yakabi, Koji; Sadakane, Chiharu; Noguchi, Masamichi; Ohno, Shino; Ro, Shoki; Chinen, Katsuya; Aoyama, Toru; Sakurada, Tomoya; Takabayashi, Hideaki; Hattori, Tomohisa

    2010-08-01

    Although chemotherapy with cisplatin is a widely used and effective cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients' quality of life. To elucidate the mechanism underlying chemotherapy-induced anorexia, focusing on the hypothalamic ghrelin secretion-anorexia association, we measured hypothalamic ghrelin secretion in fasted and cisplatin-treated rats. Hypothalamic ghrelin secretion changes after vagotomy or administration of cisplatin. Cisplatin + rikkunshito, a serotonin 2C receptor antagonist or serotonin 3 receptor antagonist, was investigated. The effects of intracerebroventricular (icv) administration of ghrelin or the serotonin 2C receptor antagonist SB242084 on food intake were also evaluated in cisplatin-treated rats. Hypothalamic ghrelin secretion significantly increased in 24-h-fasted rats compared to freely fed rats and was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, although their plasma ghrelin levels were comparable. In cisplatin-treated rats, icv ghrelin administration reversed the decrease in food intake, vagotomy partially restored hypothalamic ghrelin secretion, and hypothalamic serotonin 2C receptor mRNA expression increased significantly. Administration of rikkunshito (an endogenous ghrelin enhancer) or a serotonin 2C receptor antagonist reversed the decrease in hypothalamic ghrelin secretion and food intake 24 h after cisplatin treatment. Cisplatin-induced anorexia is mediated through reduced hypothalamic ghrelin secretion. Cerebral serotonin 2C receptor activation partially induces decrease in hypothalamic ghrelin secretion, and rikkunshito suppresses cisplatin-induced anorexia by enhancing this secretion.

  3. Oral Morphine Consumption Reduces Lens Development in Rat Embryos

    Directory of Open Access Journals (Sweden)

    Hossein Bahadoran

    2012-07-01

    Full Text Available Objective: Consumption of morphine, during pregnancy, in addition to inducing defects in the mother’s nervous system function, caused defects or delays in the formation and evolution of embryonic visual system. In the present study, changes in lens development was assessed in embryos exposed in utero to morphine. Material and Methods: Female Wistar rats (250-300 g were mated with male rats and pregnancy was determined by sperm observation in vaginal smear. This day was considered as embryonic day zero (E0. The females were then divided randomly into the experimental and the control groups. The control group received tap water and the experimental group received morphine (0.05 mg/ml in their water. On embryonic day 13 ( E13, blood samples were collected from the retro-orbital sinus of all animals for plasma corticosterone detection. On embryonic day 17(E17, the animals were killed by an overdose of chloroform and the embryos were taken out surgically. The embryos were fixed in 10% formalin for 30 days. At this time, the head of the embryos were removed for tissue processing and Hematoxylin- Eosin (H&E staining. The samples were evaluated using light microscope and MOTIC software. Results: Our data indicated that plasma corticosterone level was dramatically increased and the lens was thinner in the experimental group. (Although the proliferation of lens cells increased in the experiment group but that lens had delay in removing the proliferated and elongation cells with abnormal density in the lateral part of the lens in compare with control group. I have no idea what the authors are stating here. Moreover, the opening of the eyelids was delayed in the off springs of the mothers who received morphine. Conclusions: This study showed that morphine consumption during pregnancy leads to defects in fetal visual system development, particularly in the lens, and eyelids.

  4. Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats.

    Science.gov (United States)

    Atta, Hussein; El-Rehany, Mahmoud; Roeb, Elke; Abdel-Ghany, Hend; Ramzy, Maggie; Gaber, Shereen

    2016-02-01

    Postoperative peritoneal adhesions continue to be a major source of morbidity and occasional mortality. Studies have shown that matrix metalloproteinase-9 (MMP-9) levels are decreased postoperatively which may limits matrix degradation and participate in the development of peritoneal adhesions. In this proof-of-principle study, we evaluated the effect of gene therapy with catalytically inactive mutant MMP-9 on postoperative peritoneal adhesions in rats. Adenovirus encoding mutant MMP-9 (Ad-mMMP-9) or saline was instilled in the peritoneal cavity after cecal and parietal peritoneal injury in rats. Expression of mutant MMP-9 transcript was verified by sequencing. Adenovirus E4 gene expression, adhesion scores, MMP-9, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-β1 (TGF-β1) expression were evaluated at sacrifice one week after treatment. Both mutant MMP-9 transcripts and adenovirus E4 gene were expressed in Ad-mMMP-9 treated adhesions. Adhesions severity decreased significantly (p = 0.036) in the Ad-mMMP-9-treated compared with saline-treated adhesions. Expression of MMP-9 mRNA and protein were elevated (p = 0.001 and p = 0.029, respectively) in the Ad-mMMP-9-treated adhesions compared with saline-treated adhesions. While tPA levels were increased (p = 0.02) in Ad-mMMP-9 treated adhesions compared with saline-treated adhesions, TGF-β1 and PAI-1 levels were decreased (p = 0.017 and p = 0.042, respectively). No difference in mortality were found between groups (p = 0.64). Mutant MMP-9 gene therapy effectively transduced peritoneal adhesions resulting in reduction of severity of primary peritoneal adhesions. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  5. Inhibition of cyclooxygenase-2 reduces hypothalamic excitation in rats with adriamycin-induced heart failure.

    Directory of Open Access Journals (Sweden)

    Min Zheng

    Full Text Available BACKGROUND: The paraventricular nucleus (PVN of the hypothalamus plays an important role in the progression of heart failure (HF. We investigated whether cyclooxygenase-2 (COX-2 inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS and renin-angiotensin system (RAS in rats with adriamycin-induced heart failure. METHODOLOGY/PRINCIPAL FINDING: Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg/kg. On day 19, rats received intragastric administration daily with either COX-2 inhibitor celecoxib (CLB or normal saline. Treatment with CLB reduced mortality and attenuated both myocardial atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle to body weight (VW/BW and lung to body weight (LW/BW ratios, heart rate (HR, left ventricular end-diastolic pressure (LVEDP, left ventricular peak systolic pressure (LVPSP and maximum rate of change in left ventricular pressure (LV±dp/dtmax were improved in HF+CLB rats. Angiotensin II (ANG II, norepinephrine (NE, COX-2 and glutamate (Glu in the PVN were increased in HF rats. HF rats had higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium, and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated these HF-induced changes. HF rats had more COX-2-positive neurons and more corticotropin releasing hormone (CRH positive neurons in the PVN than did control rats. Treatment with CLB decreased COX-2-positive neurons and CRH positive neurons in the PVN of HF rats. CONCLUSIONS: These results suggest that PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory neurotransmitter release, which further contributes to sympathoexcitation and RAS activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor attenuates sympathoexcitation and RAS activation in adriamycin-induced heart failure.

  6. Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

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    Doaa A. Ghareeb

    2015-01-01

    Full Text Available Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL. The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE and amyloid beta precursor protein (AβPP. These changes were significantly correlated with decreased insulin degrading enzyme (IDE and beta-amyloid40 (Aβ40 and increased beta-amyloid42 (Aβ42 in the hippocampal region. Daily administration of berberine (50 mg/kg for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity.

  7. Mechanical Stimulation of the HT7 Acupuncture Point to Reduce Ethanol Self-Administration in Rats

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    Suk-Yun Kang

    2017-01-01

    Full Text Available Background. Alcoholism, which is a disabling addiction disorder, is a major public health problem worldwide. The present study was designed to determine whether the application of acupuncture at the Shenmen (HT7 point suppresses voluntary alcohol consumption in addicted rats and whether this suppressive effect is potentiated by the administration of naltrexone. Methods. Rats were initially trained to self-administer a sucrose solution by operating a lever. A mechanical acupuncture instrument (MAI for objective mechanical stimulation was used on rats whose baseline response had been determined. In addition, the effect of HT7 acupuncture on beta-endorphin concentration and ethanol intake via naltrexone were investigated in different groups. Results. We found that ethanol intake and beta-endorphin level in rats being treated with the MAI at the HT7 point reduced significantly. The treatment of naltrexone at high doses reduced the ethanol intake and low-dose injection of naltrexone in conjunction with the MAI also suppressed ethanol intake. Conclusions. The results of the current study indicate that using the MAI at the HT7 point effectively reduces ethanol consumption in rats. Furthermore, the coadministration of the MAI and a low dose of naltrexone can produce some more potent reducing effect of ethanol intake than can acupuncture alone.

  8. Immunoneutralization of endogenous glucagon-like peptide-2 reduces adaptive intestinal growth in diabetic rats

    DEFF Research Database (Denmark)

    Hartmann, Bolette; Thulesen, Jesper; Hare, Kristine Juul

    2002-01-01

    in the proximal part of the small intestine (10.84+/-0.44 mm(2)). Antibody treatment had no effect on body weight, blood glucose concentrations and food intake. Thus, blocking of endogenous GLP-2 in a model of adaptive intestinal growth reduces the growth response, providing strong evidence for a physiological......Supraphysiological doses of glucagon-like peptide-2 (GLP-2) have been shown to induce intestinal growth by increasing villus height and crypt depth and by decreasing apoptosis, but a physiological effect of GLP-2 has not yet been demonstrated. Earlier, we found elevated levels of endogenous GLP-2...... in untreated streptozotocin diabetic rats associated with marked intestinal growth. In the present study, we investigated the role of endogenous GLP-2 for this adaptive response. We included four groups of six rats: (1) diabetic rats treated with saline, (2) diabetic rats treated with non-specific antibodies...

  9. Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats

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    Suhana Samat

    2017-01-01

    Full Text Available Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

  10. Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats.

    Science.gov (United States)

    Samat, Suhana; Kanyan Enchang, Francis; Nor Hussein, Fuzina; Wan Ismail, Wan Iryani

    2017-01-01

    Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

  11. Ranitidine reduced levodopa-induced dyskinesia in a rat model of Parkinson’s disease

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    Cui G

    2013-12-01

    Full Text Available Guiyun Cui,1,* Xinxin Yang,1,* Xiaoying Wang,2,* Zunsheng Zhang,1 Xuanye Yue,1 Hongjuan Shi,1 Xia Shen11Department of Neurology, 2Department of Ultrasound, the Affiliated Hospital of Xuzhou Medical College, Jiangsu, People’s Republic of China *These authors contributed equally to this workBackground: Chronic administration of levodopa in Parkinson’s disease leads to debilitating involuntary movements, termed levodopa-induced dyskinesia (LID. The pathogenesis of LID is poorly understood. Previous research has shown that histamine H2 receptors are highly expressed in the input (striatum and output (globus pallidus, substantia nigra regions of the basal ganglia, particularly in the GABAergic striatopallidal and striatonigral pathways. Therefore, a histamine H2 receptor antagonist could be used to reduce LID. In the present work, we investigated whether ranitidine has the potential to diminish LID in rats with dyskinesia and explored the underlying mechanisms involved.Methods: A rat model of PD was induced by 6-hydroxydopamine. Valid PD rats were then treated with levodopa (25 mg/kg, intraperitoneally and benserazide (12.5 mg/kg, intraperitoneally for 21 days to induce a rat model of LID. The acute and chronic effects of administration of ranitidine at different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg on abnormal involuntary movements, levodopa-induced rotations, and the forelimb adjusting steps test were investigated in LID rats. The chronic effect of ranitidine (10 mg/kg on the expression of Arc and proenkephalin was also evaluated.Results: Levodopa elicited increased dyskinesia in PD rats. Acute ranitidine treatment had no effect on LID, but chronic ranitidine administration (10 mg/kg, 20 mg/kg reduced LID in rats with dyskinesia. Importantly, levodopa-induced rotations were not affected by chronic treatment with ranitidine. In addition, chronic ranitidine (10 mg/kg, 20 mg/kg significantly improved stepping of the lesioned forepaw. Real

  12. Placental Underperfusion in a Rat Model of Intrauterine Growth Restriction Induced by a Reduced Plasma Volume Expansion.

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    Karine Bibeau

    Full Text Available Lower maternal plasma volume expansion was found in idiopathic intrauterine growth restriction (IUGR but the link remains to be elucidated. An animal model of IUGR was developed by giving a low-sodium diet to rats over the last week of gestation. This treatment prevents full expansion of maternal circulating volume and the increase in uterine artery diameter, leading to reduced placental weight compared to normal gestation. We aimed to verify whether this is associated with reduced remodeling of uteroplacental circulation and placental hypoxia. Dams were divided into two groups: IUGR group and normal-fed controls. Blood velocity waveforms in the main uterine artery were obtained by Doppler sonography on days 14, 18 and 21 of pregnancy. On day 22 (term = 23 days, rats were sacrificed and placentas and uterine radial arteries were collected. Diameter and myogenic response of uterine arteries supplying placentas were determined while expression of hypoxia-modulated genes (HIF-1α, VEGFA and VEGFR2, apoptotic enzyme (Caspase -3 and -9 and glycogen cells clusters were measured in control and IUGR term-placentas. In the IUGR group, impaired blood velocity in the main uterine artery along with increased resistance index was observed without alteration in umbilical artery blood velocity. Radial uterine artery diameter was reduced while myogenic response was increased. IUGR placentas displayed increased expression of hypoxia markers without change in the caspases and increased glycogen cells in the junctional zone. The present data suggest that reduced placental and fetal growth in our IUGR model may be mediated, in part, through reduced maternal uteroplacental blood flow and increased placental hypoxia.

  13. Systemic propranolol acts centrally to reduce conditioned fear in rats without impairing extinction.

    Science.gov (United States)

    Rodriguez-Romaguera, Jose; Sotres-Bayon, Francisco; Mueller, Devin; Quirk, Gregory J

    2009-05-15

    Previous work has implicated noradrenergic beta-receptors in the consolidation and reconsolidation of conditioned fear. Less is known, however, about their role in fear expression and extinction. The beta-receptor blocker propranolol has been used clinically to reduce anxiety. With an auditory fear conditioning task in rats, we assessed the effects of systemic propranolol on the expression and extinction of two measures of conditioned fear: freezing and suppression of bar-pressing. One day after receiving auditory fear conditioning, rats were injected with saline, propranolol, or peripheral beta-receptor blocker sotalol (both 10 mg/kg, IP). Twenty minutes after injection, rats were given either 6 or 12 extinction trials and were tested for extinction retention the following day. The effect of propranolol on the firing rate of neurons in prelimbic (PL) prefrontal cortex was also assessed. Propranolol reduced freezing by more than 50%, an effect that was evident from the first extinction trial. Suppression was also significantly reduced. Despite this, propranolol had no effect on the acquisition or retention of extinction. Unlike propranolol, sotalol did not affect fear expression, although both drugs significantly reduced heart rate. This suggests that propranolol acts centrally to reduce fear. Consistent with this, propranolol reduced the firing rate of PL neurons. Propranolol reduced the expression of conditioned fear, without interfering with extinction learning. Reduced fear with intact extinction suggests a possible use for propranolol in reducing anxiety during extinction-based exposure therapies, without interfering with long-term clinical response.

  14. Tofacitinib attenuates arthritis manifestations and reduces the pathogenic CD4 T cells in adjuvant arthritis rats.

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    Gertel, Smadar; Mahagna, Hussein; Karmon, Gidi; Watad, Abdulla; Amital, Howard

    2017-11-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by pronounced inflammation and leukocyte infiltration in affected joints. Tofacitinib is new agent, a selective inhibitor of Janus kinase (JAK) signaling pathways mediated by JAK1 and JAK3 and inhibits the key transcription factors STAT1 and STAT3. We investigated the action mechanisms of tofacitinib in rats with adjuvant-induced-arthritis (AIA). AIA-rats were treated orally with tofacitinib or with methotrexate. Arthritis severity and serum C-reactive protein (CRP) levels were evaluated, splenic cells were examined by flow cytometry and cytokines were analyzed by real-time PCR. Tofacitinib markedly reduced the clinical status of treated rats in comparison to control group. Reduced joints inflammation and down-regulated serum CRP levels reflected the clinical manifestations of the treated rats. Tofacitinib down-regulated significantly the frequency of CD4 + IFN-γ + T cells and reduced IL-1β mRNA expression levels in the spleen of the treated rats. These results show that tofacitinib attenuated arthritis severity, modified splenic populations and cytokine imbalance. Copyright © 2017. Published by Elsevier Inc.

  15. Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus.

    Science.gov (United States)

    Reyes-Haro, Daniel; Labrada-Moncada, Francisco Emmanuel; Varman, Durairaj Ragu; Krüger, Janina; Morales, Teresa; Miledi, Ricardo; Martínez-Torres, Ataúlfo

    2016-01-01

    Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (-23%) and dentate gyrus (-48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression.

  16. Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

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    Tufik Sergio

    2007-03-01

    Full Text Available Abstract Background Paradoxical sleep deprivation (PSD associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. Methods The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group. To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg or testosterone (0.5 mg/kg or 1.0 mg/kg administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. Results A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role

  17. Orofacial neuropathic pain reduces spontaneous burrowing behavior in rats.

    Science.gov (United States)

    Deseure, K; Hans, G

    2018-07-01

    It was recently reported that spontaneous burrowing behavior is decreased after tibial nerve transection, spinal nerve transection and partial sciatic nerve ligation. It was proposed that spontaneous burrowing could be used as a measure of the impact of neuropathic pain after peripheral nerve injury. It has remained unclear whether the reduction in burrowing behavior is caused directly by pain or hypersensitivity in the affected limbs, making it more difficult to perform burrowing, or by a pain induced decrease in the general wellbeing, thus reducing the motivation to burrow. We studied burrowing behavior after infraorbital nerve injury, a model of orofacial neuropathic pain that does not affect the limbs. Burrowing behavior was significantly reduced after infraorbital nerve injury. Isolated face grooming and responsiveness to mechanical von Frey stimulation of the infraorbital nerve territory were significantly increased after infraorbital nerve injury, indicative, respectively, of spontaneous pain and mechanical allodynia. It is concluded that spontaneous burrowing may provide a measure of the global impact of pain on the animal's wellbeing after peripheral nerve injury and incorporation of this behavioral assay in preclinical drug testing may improve the predictive validity of currently used pain models. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Weight Loss and Melatonin Reduce Obesity-Induced Oxidative Damage in Rat Testis

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    Dogan Atilgan

    2013-01-01

    Full Text Available Aim. We aimed to evaluate the antioxidant effects of weight loss and melatonin on the obesity-induced oxidative damage in rat testes. Materials and Methods. 28 male Wistar albino rats were randomly divided into 4 groups, each consisting of 7 rats: control group (Group 1, obesity group (Group 2, obesity + MLT group (Group 3, and weight loss group (Group 4. Rats were weighed at the beginning and at the end of the study. Bilateral orchiectomy was performed and 5 cc blood samples were obtained from all of the rats. Superoxide dismutase (SOD, malondialdehyde (MDA, and protein carbonyl (PC levels were analysed in the testicular tissues and serum. Spermatogenesis was evaluated with the Johnsen scoring system. Results. The testicular tissue and serum levels of MDA, PC, and SOD activity were increased in the obesity group in comparison to the sham operated group (P<0.05. Weight loss and melatonin treatment ameliorated MDA, PC, and SOD levels in testicular tissue and serum significantly (P<0.05. There was no significant difference between groups in terms of mean Johnsen score (P=0.727. Conclusion. Experimentally created obesity caused oxidative stress and both melatonin and weight loss reduced oxidative stress parameters in rat testes.

  19. Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

    Science.gov (United States)

    Vilaseca, Marina; García-Calderó, Héctor; Lafoz, Erica; Ruart, Maria; López-Sanjurjo, Cristina Isabel; Murphy, Michael P; Deulofeu, Ramon; Bosch, Jaume; Hernández-Gea, Virginia; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

    2017-07-01

    In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl 4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl 4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. A fibre cocktail of fenugreek, guar gum and wheat bran reduces oxidative modification of LDL induced by an atherogenic diet in rats.

    Science.gov (United States)

    Venkatesan, Nandini; Devaraj, S Niranjali; Devaraj, H

    2007-01-01

    LDL (low-density lipoprotein) oxidation is a key trigger factor for the development of atherosclerosis. Relatively few studies exist on the impact of dietary fibre on LDL oxidation. This study was undertaken to evaluate the influence of a novel fibre mix of fenugreek seed powder, guar gum and wheat bran (Fibernat) on LDL oxidation induced by an atherogenic diet. Male Wistar albino rats were administered one of the following diets: (1) a control diet that was fibre-free (Group I); (2) an atherogenic diet containing 1.5% cholesterol and 0.1% cholic acid (Group II) or (3) an atherogenic diet supplemented with Fibernat (Group III). Peroxidative changes in low-density lipoprotein (LDL) and the oxidative susceptibility of LDL and the LDL + VLDL (very low-density lipoprotein) fraction were determined. As a corollary to the oxidative modification theory, the titer of autoantibodies to oxidised LDL (oxLDL) was determined at various time points of the study. In addition, plasma homocysteine (tHcy) and lipoprotein (Lp (a)), apolipoprotein (apoB), cholesterol, triglyceride, phospholipid and alpha-tocopherol content of LDL were determined. A decrease in malonaldehyde (MDA) content (p<0.05) and relative electrophoretic mobility (REM) of LDL was observed in the group III rats as compared to the group II rats. An increase in lag time to oxidation (p<0.01) and decrease in maximum oxidation (p<0.01) and oxidation rate (p<0.01) were observed in the LDL + VLDL fraction of group III rats. In group II rats, formation of autoantibodies to oxLDL occurred at an earlier time point and at levels greater than in the group III rats. Fibernat, had a sparing effect on LDL alpha-tocopherol, which was about 51% higher in the group III rats than in the group II rats; apo B content of LDL was reduced by 37.6% in group III rats. LDL of group III rats displayed a decrease in free and ester cholesterol (p<0.01) as compared to that of group II. A decrease in plasma homocysteine (p<0.01) and an increase

  1. Injected phage-displayed-VP28 vaccine reduces shrimp Litopenaeus vannamei mortality by white spot syndrome virus infection.

    Science.gov (United States)

    Solís-Lucero, G; Manoutcharian, K; Hernández-López, J; Ascencio, F

    2016-08-01

    White spot syndrome virus (WSSV) is the most important viral pathogen for the global shrimp industry causing mass mortalities with huge economic losses. Recombinant phages are capable of expressing foreign peptides on viral coat surface and act as antigenic peptide carriers bearing a phage-displayed vaccine. In this study, the full-length VP28 protein of WSSV, widely known as potential vaccine against infection in shrimp, was successfully cloned and expressed on M13 filamentous phage. The functionality and efficacy of this vaccine immunogen was demonstrated through immunoassay and in vivo challenge studies. In ELISA assay phage-displayed VP28 was bind to Litopenaeus vannamei immobilized hemocyte in contrast to wild-type M13 phage. Shrimps were injected with 2 × 10(10) cfu animal(-1) single dose of VP28-M13 and M13 once and 48 h later intramuscularly challenged with WSSV to test the efficacy of the vaccine against the infection. All dead challenged shrimps were PCR WSSV-positive. The accumulative mortality of the vaccinated and challenged shrimp groups was significantly lower (36.67%) than the unvaccinated group (66.67%). Individual phenoloxidase and superoxide dismutase activity was assayed on 8 and 48 h post-vaccination. No significant difference was found in those immunological parameters among groups at any sampled time evaluated. For the first time, phage display technology was used to express a recombinant vaccine for shrimp. The highest percentage of relative survival in vaccinated shrimp (RPS = 44.99%) suggest that the recombinant phage can be used successfully to display and deliver VP28 for farmed marine crustaceans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Repeated administration of amitriptyline reduces oxaliplatin-induced mechanical allodynia in rats.

    Science.gov (United States)

    Sada, Hikaru; Egashira, Nobuaki; Ushio, Soichiro; Kawashiri, Takehiro; Shirahama, Masafumi; Oishi, Ryozo

    2012-01-01

    Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Amitriptyline has widely been used in patients with painful neuropathy. In this study, we investigated the effect of amitriptyline on the oxaliplatin-induced neuropathy in rats. Repeated administration of amitriptyline (5 and 10 mg/kg, p.o., once a day) reduced the oxaliplatin-induced mechanical allodynia but not cold hyperalgesia and reversed the oxaliplatin-induced increase in the expression of NR2B protein and mRNA in rat spinal cord. These results suggest that amitriptyline is useful for the treatment of oxaliplatin-induced neuropathy clinically.

  3. Exendin-4 reduces tau hyperphosphorylation in type 2 diabetic rats via increasing brain insulin level.

    Science.gov (United States)

    Yang, Yan; Ma, Delin; Xu, Weijie; Chen, Fuqiong; Du, Tingting; Yue, Wenzhu; Shao, Shiying; Yuan, Gang

    2016-01-01

    Type 2 diabetes (T2D) is a high risk factor for Alzheimer's disease (AD). Our previous study identified that hyperphosphorylation of tau protein, which is one of the pathophysiologic hallmarks of AD, also occurred in T2D rats' brain; while glucagon-like peptide-1 (GLP-1) mimetics, a type of drug used in T2D, could decrease the phosphorylation of tau, probably via augmenting insulin signaling pathway. The purpose of this study was to further explore the mechanisms that underlie the effect of exendin-4 (ex-4, a GLP-1 receptor agonist) in reducing tau phosphorylation. We found that peripheral ex-4 injection in T2D rats reduced hyperphosphorylation of tau protein in rat hippocampus, probably via increasing hippocampal insulin which activated insulin signaling. Furthermore, we found that ex-4 could neither activate insulin signaling, nor reduce tau phosphorylation in HT22 neuronal cells in the absence of insulin. These results suggested that insulin is required in reduction of tau hyperphosphorylation by ex-4 in brain rats with T2D. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Naloxone and rimonabant reduce the reinforcing properties of exercise in rats.

    Science.gov (United States)

    Rasmussen, Erin B; Hillman, Conrad

    2011-12-01

    Naloxone and rimonabant block neurotransmitter action of some drugs of abuse (such as ethanol, opiates, and nicotine), and thereby reduce drug seeking and self-administration by suppressing the drugs' reinforcing properties. The present study represents an attempt to elucidate whether these drugs may also reduce rewarding properties of other events, in this case, activity-based reinforcement. In Experiment 1, 10 obese and 10 lean Zucker rats pressed a locked door under a progressive ratio schedule of reinforcement that, when unlocked, provided access to a running wheel for 2-min intervals. After baseline breakpoints were established, doses of naloxone (0.3-10 mg/kg) were administered prior to experimental sessions. Obese rats exhibited lower baseline breakpoints for wheel activity, lower response rates, and fewer revolutions compared to lean rats. Naloxone decreased revolutions and response rates for lean and obese rats, but did not reduce breakpoints. In Experiment 2, five Long-Evans rats pressed a door to unlock a wheel for 20 s of wheel activity. Doses of rimonabant (1-10 mg/kg) were administered before some experimental sessions. The highest dose of rimonabant suppressed breakpoints and response rates, but did not affect revolutions. These data suggest that both drugs reduce the reinforcing properties of wheel running, but do so in different manners: naloxone may suppress wheel-based activity (consummatory behavior), but not seeking (appetitive behavior), and rimonabant does the converse. The data also support the role of endocannabinoids in the reinforcing properties of exercise, an implication that is important in terms of CB1 antagonists as a type of pharmacotherapy.

  5. Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats.

    Science.gov (United States)

    Song, Yu; Liu, Junxiu; Ma, Furong; Mao, Lanqun

    2016-12-01

    Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally.

  6. 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.

  7. Dipyridamole reduces penile apoptosis in a rat model of post-prostatectomy erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Omer Kutlu

    Full Text Available ABSTRACT Purpose: Despite the nerve-sparing technique, many patients suffer from erectile dysfunction after radical prostatectomy (RP due to cavernous nerve injury. The aim of this study was to evaluate dipyridamole as a potential treatment agent of post-radical prostatectomy erectile dysfunction. Material and methods: A total of 18 male Sprague-Dawley rats were randomized into three experimental Groups (SHAM+DMSO, BCNI+DMSO and BCNI+DIP. An animal model of bilateral cavernous nerve crush injury (BCNI was established to mimic the partial nerve damage during nerve-sparing RP. After creating of BCNI, dimethyl sulphoxide (DMSO was administered transperitoneally as a vehicle to SHAM+DMSO and BCNI+DMSO Groups. BCNI+DIP Group received dipyiridamole (10mg/kg/day as a solution in DMSO for 15 days. Afterwards, rats were evaluated for in vivo erectile response to cavernous nerve stimulation. Penile tissues were also analyzed biochemically for transforming growth factor-β1 (TGF-β1 level. Penile corporal apoptosis was determined by TUNEL method. Results: Erectile response was decreased in rats with BCNI and there was no significant improvement with dipyridamole treatment. TGF-β1 levels were increased in rats with BCNI and decreased with dipyridamole treatment. Dipyridamole led to reduced penile apoptosis in rats with BCNI and there was no significant difference when compared to sham operated rats. Conclusions: Although fifteen-day dipyridamole treatment has failed to improve erectile function in rats with BCNI, the decline in both TGF-β1 levels and apoptotic indices with treatment may be helpful in protecting penile morphology after cavernous nerve injury.

  8. Nicardipine reduces calcium accumulation and electrolyte derangements in regional cerebral ischemia in rats

    International Nuclear Information System (INIS)

    Hadani, M.; Young, W.; Flamm, E.S.

    1988-01-01

    We studied the effects of the calcium channel blocker nicardipine on regional tissue Ca 2+ , Na + , K + , and water shifts in the brains of seven Sprague-Dawley rats after permanent occlusions of the middle cerebral artery. We also assessed the entry of [ 14 C]nicardipine into the brains of five rats; the highest concentrations of [ 14 C]nicardipine were in the infarcted area. Nicardipine treatment significantly reduced Ca 2+ accumulation in the middle cerebral artery territory by 60% compared with six untreated rats 6 hours after arterial occlusion. Eight 125-micrograms/kg boluses of nicardipine given every 30 minutes starting 5 minutes after arterial occlusion also significantly reduced the Na + and K + shifts in the middle cerebral artery territory by 40% and 50%, respectively, 6 hours after arterial occlusion. Nicardipine appears to reduce Ca 2+ accumulation more than it reduces Na + and water accumulation and K + loss. Our results suggest that a calcium channel blocker can protect brain tissues in a model of focal cerebral infarction by directly reducing Ca 2+ entry into ischemic cells

  9. Lactobacillus paracasei HII01, xylooligosaccharides, and synbiotics reduce gut disturbance in obese rats.

    Science.gov (United States)

    Thiennimitr, Parameth; Yasom, Sakawdaurn; Tunapong, Wannipa; Chunchai, Titikorn; Wanchai, Keerati; Pongchaidecha, Anchalee; Lungkaphin, Anusorn; Sirilun, Sasithorn; Chaiyasut, Chaiyavat; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2018-03-20

    The beneficial effects of pro-, pre-, and synbiotics on obesity with insulin resistance have been reported previously. However, the strain-specific effect of probiotics and the combination with various types of prebiotic fiber yield controversial outcomes and limit clinical applications. Our previous study demonstrated that the probiotic Lactobacillus paracasei (L. paracasei) HII01, prebiotic xylooligosaccharide (XOS), and synbiotics share similar efficacy in attenuating cardiac mitochondrial dysfunction in obese-insulin resistant rats. Nonetheless, the roles of HII01 and XOS on gut dysbiosis and gut inflammation under obese-insulin resistant conditions have not yet, to our knowledge, been investigated. Our hypothesis was that pro-, pre-, and synbiotics improve the metabolic parameters in obese-insulin resistant rats by reducing gut dysbiosis and gut inflammation. Male Wistar rats were fed with either a normal or high-fat diet that contained 19.77% and 59.28% energy from fat, respectively, for 12 wk. Then, the high-fat diet rats were fed daily with a 10 8 colony forming unit of the probiotic HII01, 10% prebiotic XOS, and synbiotics for 12 wk. The metabolic parameters, serum lipopolysaccharide levels, fecal Firmicutes/Bacteroidetes ratios, levels of Enterobacteriaceae, Bifidobacteria, and gut proinflammatory cytokine gene expression were quantified. The consumption of probiotic L. paracasei HII01, prebiotic XOS, and synbiotics for 12 wk led to a decrease in metabolic endotoxemia, gut dysbiosis (a reduction in the Firmicutes/Bacteroidetes ratio and Enterobacteriaceae), and gut inflammation in obese-insulin resistant rats. Pro-, pre-, and synbiotics reduced gut dysbiosis and gut inflammation, which lead to improvements in metabolic dysfunction in obese-insulin resistant rats. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Myenteric denervation differentially reduces enteroendocrine serotonin cell population in rats during postnatal development.

    Science.gov (United States)

    Hernandes, Luzmarina; Fernandes, Marilda da Cruz; Pereira, Lucieni Cristina Marques da Silva; Freitas, Priscila de; Gama, Patrícia; Alvares, Eliana Parisi

    2006-05-01

    The enteric nervous and enteroendocrine systems regulate different processes in the small intestine. Ablation of myenteric plexus with benzalkonium chloride (BAC) stimulates epithelial cell proliferation, whereas endocrine serotonin cells may inhibit the process. To evaluate the connection between the systems and the influence of myenteric plexus on serotoninergic cells in rats during postnatal development, the ileal plexus was partially removed with BAC. Rats were treated at 13 or 21 days and sacrificed after 15 days. The cell bodies of myenteric neurons were stained by beta NADH-diaphorase to detect the extension of denervation. The number of enteroendocrine cells in the ileum was estimated in crypts and villi in paraffin sections immunostained for serotonin. The number of neurons was reduced by 27.6 and 45% in rats treated on the 13th and 21st days, respectively. We tried to establish a correlation of denervation and the serotonin population according to the age of treatment. We observed a reduction of immunolabelled cells in the crypts of rats treated at 13 days, whereas this effect was seen in the villi of rats denervated at 21 days. These results suggest that the enteric nervous system might control the enteroendocrine cell population and this complex mechanism could be correlated to changes in cell proliferation.

  11. Mangosteen peel extract reduces formalin-induced liver cell death in rats

    Directory of Open Access Journals (Sweden)

    Afiana Rohmani

    2014-08-01

    Full Text Available Background Formalin is a xenobiotic that is now commonly used as a preservative in the food industry. The liver is an organ that has the highest metabolic capacity as compared to other organs. Mangosteen or Garcinia mangostana Linn (GML peel contains xanthones, which are a source of natural antioxidants. The purpose of this study was to evaluate the effect of mangosteen peel extract on formalin-induced liver cell mortality rate and p53 protein expression in Wistar rats. Methods Eighteen rats received formalin orally for 2 weeks, and were subsequently divided into 3 groups, consisting of the formalin-control group receiving a placebo and treatment groups 1 and 2, which were treated with mangosteen peel extract at doses of 200 and 400 mg/kgBW/day, respectively. The treatment was carried out for 1 week, and finally the rats were terminated. The differences in liver cell mortality rate and p53 protein expression were analyzed. Results One-way ANOVA analysis showed significant differences in liver cell mortality rate among the three groups (p=0.004. The liver cell mortality rate in the treatment group receiving 400 mg/kgBW/day extract was lower than that in the formalin-control group. There was no p53 expression in all groups. Conclusions Garcinia mangostana Linn peel extract reduced the mortality rate of liver cells in rats receiving oral formalin. Involvement of p53 expression in liver cell mortality in rats exposed to oral formalin is presumably negligible.

  12. Juvenile Male Rats Exposed to a Low-Dose Mixture of Twenty-Seven Environmental Chemicals Display Adverse Health Effects

    DEFF Research Database (Denmark)

    Hadrup, Niels; Svingen, Terje; Egebjerg, Karen Mandrup

    2016-01-01

    of 27 chemicals administered orally to juvenile male rats for three months could leave a pathophysiological footprint. The mixture contained metals, perfluorinated compounds, PCB, dioxins, pesticides, heterocyclic amines, phthalate, PAHs and others, with a combined dose of 0.16 (Low dose), 0.47 (Mid...

  13. Chicken collagen type II reduces articular cartilage destruction in a model of osteoarthritis in rats.

    Science.gov (United States)

    Xu, D; Shen, W

    2007-06-01

    To evaluate the therapeutic effects of domestic chicken collagen type II (CCII) on rat osteoarthritis (OA) and analyze concomitant changes in the level of Matrix metalloproteinase (MMP)-13, MMP-9, Cathepsin K and their mRNA as well as the tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA in articular cartilage of osteoarthritic rats. Osteoarthritis models were surgically induced. Morphology of articular cartilage was done by haematoxylin and eosin staining and Mankin score was calculated, immunohistochemistry of MMP-13, MMP-9 and Cathepsin K was done by ABC method while the mRNA level for MMP-13, MMP-9, cathepsin K as well as TIMP-1 was evaluated by RT-PCR method. Oral administration of CCII reduced the morphological changes of osteoarthritic cartilage (shown by Mankin score), decreased levels of MMP-13, MMP-9, cathepsin K as well as their mRNA in articular cartilage from osteoarthritic rats while it exhibited no effect on TIMP-1 mRNA. Oral CCII reduced articular cartilage degradation of osteoarthritic rats and may probably be a potent drug candidate for OA treatment.

  14. Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome.

    Science.gov (United States)

    Kusaka, Hiroaki; Koibuchi, Nobutaka; Hasegawa, Yu; Ogawa, Hisao; Kim-Mitsuyama, Shokei

    2016-11-11

    The potential benefit of SGLT2 inhibitors in metabolic syndrome is with prediabetic stage unclear. This work was undertaken to investigate the non-glycemic effect of empagliflozin on metabolic syndrome rats with prediabetes. SHR/NDmcr-cp(+/+) rats (SHRcp), a model of metabolic syndrome with prediabetes, were given empagliflozin for 10 weeks to examine the effects on urinary sodium and water balance, visceral and subcutaneous adipocyte, and cardiac injury. Further, the effect of empagliflozin on blood pressure and autonomic nervous system was continuously investigated by using radiotelemetry system. Empagliflozin significantly reduced urinary sodium and water balance of SHRcp only within 1 week of the treatment, but later than 1 week did not alter them throughout the treatment. Empagliflozin significantly reduced body weight of SHRcp, which was mainly attributed to the significant reduction of subcutaneous fat mass. Empagliflozin significantly reduced the size of visceral adipocytes and increased the number of smaller size of adipocytes, which was associated with the attenuation of oxidative stress. Empagliflozin ameliorated cardiac hypertrophy and fibrosis of SHRcp, in association with the attenuation of cardiac oxidative stress and inflammation. However, empagliflozin did not significantly change blood pressure, heart rate, sympathetic activity, or baroreceptor function, as evidenced by radiotelemetry analysis. Our present work provided the evidence that SGLT2 inhibition reduced visceral adipocytes hypertrophy and ameliorated cardiac injury in prediabetic metabolic syndrome rat, independently of diuretic effect or blood pressure lowering effect. Thus, SGLT2 inhibition seems to be a promising therapeutic strategy for prediabetic metabolic syndrome.

  15. [Study on the weight-reducing effect of Acer truncatum leave extract in alimentary obesity rat].

    Science.gov (United States)

    Gao, Lifang; Cao, Lige; Tian, Mi; Chen, Zhenliang

    2012-07-01

    To investigate the weight-reducing effect of Acer truncatum leave extract on alimentary obesity rats and its effect on fatty acid synthase (FAS). SPF-grade adult male Wistar rats were fed with high-fat diet and Acer truncatum leave extract (10, 30 and 100 mg/kg BW) was given by gavage once a day for 31 days. Body weight (BW), adipose weight and food consumption were recorded, and the activity of hepatic fatty acid synthase (FAS) was measured. Compared with the model-control group, body weight, adipose weight and the ratio of adipose weight to body weight were obviously lower in 30 mg/kg BW and 100 mg/kg BW groups (P Acer truncatum leave extract on reducing body weight.

  16. Melatonin reduces the expression of chemokines in rat with trinitrobenzene sulfonic acid-induced colitis

    International Nuclear Information System (INIS)

    Li, Jun H.; Zhou, W.; Liu, K.; Li, Hong X.; Wang, L.

    2008-01-01

    Objective was to investigate the effect of melatonin on the colon inflammatory injury of rats with colitis and determine whether this effect is associated with inhibition of chemoattractant molecules interleukins (IL-8) and monocyte chemoattractant protein (MCP)-1.The study was designed and implemented in JingMen No.1 People's Hospital, HuBei Province, from May 2006 to April 2007. It involved 72 animals divided into 6 groups of 12 each: normal group, model group, 5-aminosalisalicylic acid group, and melatonin group (dose of 2.5, 5.0 and 10.0mg/kg). Rat colitis model was established by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enema. Interleukin-8 and MCP-1 proteins in colon tissue were examined by immunohistochemistry and western blot. The messenger-RNA expressions of chemokines were determined by reverse transcription polymerase chain reaction analysis. Trinitrobenzene sulfonic acid enema resulted in pronounced pathological changes of colonic mucosa in model rats, which were in accordance with the significantly elevated Myeloperoxidase activity. Expressions of chemokines were up-regulated in colitis. Melatonin treatment reduced colonic lesions and improved colitis symptom, and decreased the protein and mRNA expressions of IL-8 and MCP-1 significantly in colon tissues of rats with colitis. Chemokines IL-8 and MCP-1 are elevated in mucosal tissues in colitis and play an important role in the perpetuation of tissue destructive inflammatory process; melatonin reduces colonic inflammatory injury of rats colitis through down-regulating the expressions of chemokines. Melatonin can be considered as a novel therapeutic alternative for the treatment of inflammatory bowel disease. (author)

  17. Broccoli (Brassica oleracea) Reduces Oxidative Damage to Pancreatic Tissue and Combats Hyperglycaemia in Diabetic Rats.

    Science.gov (United States)

    Suresh, Sithara; Waly, Mostafa Ibrahim; Rahman, Mohammad Shafiur; Guizani, Nejib; Al-Kindi, Mohamed Abdullah Badar; Al-Issaei, Halima Khalfan Ahmed; Al-Maskari, Sultan Nasser Mohd; Al-Ruqaishi, Bader Rashid Said; Al-Salami, Ahmed

    2017-12-01

    Oxidative stress plays a pivotal role in the development of diabetes and hyperglycaemia. The protective effects of natural extracts against diabetes are mainly dependent on their antioxidant and hypoglycaemic properties. Broccoli ( Brassica oleracea ) exerts beneficial health effects in several diseases including diabetes; however, the mechanism has not been elucidated yet. The present study was carried out to evaluate the potential hypoglycaemic and antioxidant properties of aqueous broccoli extracts (BEs) in diabetic rats. Streptozotocin (STZ) drug was used as a diabetogenic agent in a single intraperitoneal injection dose of 50 mg/kg body weight. The blood glucose level for each rat was measured twice a week. After 8 weeks, all animals were fasted overnight and sacrificed; pancreatic tissues were homogenized and used for measuring oxidative DNA damage, biochemical assessment of glutathione (GSH), and total antioxidant capacity (TAC) as well as histopathological examination for pancreatic tissues was examined. Diabetic rats showed significantly higher levels of DNA damage, GSH depletion, and impaired TAC levels in comparison to non-diabetics ( P <0.05). The treatment of diabetic rats with BE significantly reduced DNA damage and conserved GSH and TAC values ( P <0.01). BE attenuated pancreatic histopathological changes in diabetic rats. The results of this study indicated that BE reduced the STZ mediated hyperglycaemia and the STZ-induced oxidative injury to pancreas tissue. The used in vivo model confirmed the efficacy of BE as an anti-diabetic herbal medicine and provided insights into the capacity of BE to be used for phytoremediation purposes for human type 2 diabetes.

  18. Captopril reduces collagen and mast cell accumulation in irradiated rat lung

    International Nuclear Information System (INIS)

    Ward, W.F.; Molteni, A.; Ts'ao, C.H.; Hinz, J.M.

    1990-01-01

    The angiotensin converting enzyme inhibitor captopril ameliorates radiation-induced pulmonary endothelial dysfunction in rats. The present study determined whether captopril also reduces collagen (hydroxyproline) accumulation in the lungs of rats sacrificed 2 months after a range of single doses (0-30 Gy) of 60Co gamma rays to the right hemithorax. Captopril was administered in the feed at a regimen of 0, 25, or 50 mg/kg/day continuously after irradiation. Mast cell counts also were obtained from lungs of all animals exposed to 30 Gy. In rats receiving no captopril, there was a radiation dose-dependent increase in right lung hydroxyproline (HP) content and in HP concentration per g wet weight. Captopril produced a drug dose-dependent suppression in this radiation-induced HP accumulation. At a dose of 50 mg/kg/d, captopril reduced the slope of the radiation dose response curve for lung HP content by a factor of 1.7, and completely prevented the increase in HP concentration. At an isoeffect level of 550 micrograms HP per right superior lobe, this dose of captopril exhibited a DRF of 1.7 +/- 0.2. In rats exposed to 30 Gy, moreover, the number of mast cells per mm2 of alveolar cross-sectional surface area decreased from 105 +/- 8 to 100 +/- 7 and 59 +/- 5 in the groups given 0, 25 or 50 mg/kg/d of captopril, respectively, (vs none in sham-irradiated rats). These data are the first to demonstrate that the ACE inhibitor captopril might provide a novel intervention in the pathogenesis of radiation fibrosis

  19. Alginate enhances excretion and reduces absorption of strontium and cesium in rats

    International Nuclear Information System (INIS)

    Idota, Yoko; Harada, Hitomi; Tomono, Takumi; Morimoto, Kaori; Kakinuma, Chihaya; Ogihara, Takuo; Kobayashi, Shoko; Miyajima, Chihiro; Kasahara, Fumiyoshi

    2013-01-01

    Alginate (ALA), which is an intercellular polysaccharide associated with brown algae, is used as a food additive, a health food and a medicine. Here, we first examined the adsorption of strontium (Sr) and cesium (Cs) by ALA in vitro, and then evaluated the effects of ALA on absorption and excretion of Sr and Cs in rats, in order to evaluate its potential usefulness for minimizing radiation damage from materials released after a nuclear accident. Both Sr and Cs were concentration-dependently adsorbed by sodium alginate (ALA-Na) in vitro. In rats given diet containing either ALA-Na or calcium alginate (ALA-Ca) for two weeks, the plasma concentration of Sr gradually decreased compared with the controls (normal diet); however, in the case of Cs, the plasma concentration was decreased only in the ALA-Ca group, but not the ALA-Na group. Moreover, we examined the effect of preadministration of diet containing either ALA-Na or ALA-Ca on absorption of Sr and Cs administered orally as the chloride salts to rats. Absorption of both Sr and Cs was reduced in the ALA-Ca group, while absorption of only Sr was reduced in the ALA-Na group. Safety assessments indicated that ALA-Ca is safer than ALA-Na. These results indicate that ALA-Ca reduces absorption and promotes excretion of both Sr and Cs, while ALA-Na does so only for Sr. (author)

  20. Efficacy of curcumin to reduce hepatic damage induced by alcohol and thermally treated oil in rats

    Directory of Open Access Journals (Sweden)

    Nasr A.M.N. El-Deen

    2010-03-01

    Full Text Available The authors investigated the effect of curcumin on markers of oxidative stress and liver damage in rats that chronically ingested alcohol and heated oil. Nine groups of ten Wistar male rats received combinations of curcumin 100 mg/kg body weight daily, ethanol 5 mg/kg, 15% dietary sunflower oil and 15% heated sunflower oil for 12 weeks. Serum and liver tissue were collected. Groups 4-6, which had received compounds causing oxidative stress, showed increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, low density lipoprotein, very low density lipoprotein and reduced high density lipoprotein, protein and albumin, compared with the controls. Reductions were observed in glutathione peroxidase and reductase gene expression, superoxide dismutase activity, glutathione peroxidase activity, glutathione reductase activity, reduced glutathione concentration and catalase enzyme activity. Groups 7, 8 and 9 which received curcumin with heated oil, ethanol or both, showed lower elevations in serum and oxidative damage markers compared with the corresponding non-curcumin treated groups.It can be concluded that curcumin reduces markers of liver damage in rats treated with heated sunflower oil or ethanol.

  1. Cyclosporine A at reperfusion fails to reduce infarct size in the in vivo rat heart.

    Science.gov (United States)

    De Paulis, Damien; Chiari, Pascal; Teixeira, Geoffrey; Couture-Lepetit, Elisabeth; Abrial, Maryline; Argaud, Laurent; Gharib, Abdallah; Ovize, Michel

    2013-09-01

    We examined the effects on infarct size and mitochondrial function of ischemic (Isch), cyclosporine A (CsA) and isoflurane (Iso) preconditioning and postconditioning in the in vivo rat model. Anesthetized open-chest rats underwent 30 min of ischemia followed by either 120 min (protocol 1: infarct size assessment) or 15 min of reperfusion (protocol 2: assessment of mitochondrial function). All treatments administered before the 30-min ischemia (Pre-Isch, Pre-CsA, Pre-Iso) significantly reduced infarct as compared to control. In contrast, only Post-Iso significantly reduced infarct size, while Post-Isch and Post-CsA had no significant protective effect. As for the postconditioning-like interventions, the mitochondrial calcium retention capacity significantly increased only in the Post-Iso group (+58 % vs control) after succinate activation. Only Post-Iso increased state 3 (+177 and +62 %, for G/M and succinate, respectively) when compared to control. Also, Post-Iso reduced the hydrogen peroxide (H2O2) production (-46 % vs control) after complex I activation. This study suggests that isoflurane, but not cyclosporine A, can prevent lethal reperfusion injury in this in vivo rat model. This might be related to the need for a combined effect on cyclophilin D and complex I during the first minutes of reperfusion.

  2. Secondhand Smoke Exposure Reduced the Compensatory Effects of IGF-I Growth Signaling in the Aging Rat Hearts.

    Science.gov (United States)

    Wu, Jia-Ping; Hsieh, Dennis Jine-Yuan; Kuo, Wei-Wen; Han, Chien-Kuo; Pai, Peiying; Yeh, Yu-Lan; Lin, Chien-Chung; Padma, V Vijaya; Day, Cecilia Hsuan; Huang, Chih-Yang

    2015-01-01

    Secondhand smoke (SHS) exposure is associated with increased risk of cardiovascular disease. Aging is a physiological process that involves progressive impairment of normal heart functions due to increased vulnerability to damage. This study examines secondhand smoke exposure in aging rats to determine the age-related death-survival balance. Rats were placed into a SHS exposure chamber and exposed to smog. Old age male Sprague-Dawley rats were exposed to 10 cigarettes for 30 min, day and night, continuing for one week. After 4 weeks the rats underwent morphological and functional studies. Left ventricular sections were stained with hematoxylin-eosin for histopathological examination. TUNEL detected apoptosis cells and protein expression related death and survival pathway were analyzed using western blot. Death receptor-dependent apoptosis upregulation pathways and the mitochondria apoptosis proteins were apparent in young SHS exposure and old age rats. These biological markers were enhanced in aging SHS-exposed rats. The survival pathway was found to exhibit compensation only in young SHS-exposed rats, but not in the aging rats. Further decrease in the activity of this pathway was observed in aging SHS-exposed rats. TUNEL apoptotic positive cells were increased in young SHS-exposed rats, and in aging rats with or without SHS-exposure. Aging reduces IGF-I compensated signaling with accelerated cardiac apoptotic effects from second-hand smoke.

  3. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

    Directory of Open Access Journals (Sweden)

    José Jaime Herrera-Pérez

    2013-01-01

    Full Text Available In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT expression associated with low testosterone (T levels. The objectives of this study were to establish (1 if brain SERT expression is reduced by aging and (2 if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population.

  4. Dietary restriction of choline reduces hippocampal acetylcholine release in rats: in vivo microdialysis study.

    Science.gov (United States)

    Nakamura, A; Suzuki, Y; Umegaki, H; Ikari, H; Tajima, T; Endo, H; Iguchi, A

    2001-12-01

    We fed rats with a diet deficient in choline for 12 weeks and studied how dietary choline deficiency affected their behavior and their ability to release acetylcholine in discrete regions of rat brain using step-through passive avoidance task and in vivo microdialysis. In comparison with the control, rats fed the choline-deficient diet showed poorer retention of nociceptive memory in the passive avoidance task. Average choline level in cerebrospinal fluid in the choline-deficient group was significantly less (33.1%) than that of control rats. In vivo microdialysis showed no difference in the pattern of acetylcholine release enhanced by intraperitoneal administration of scopolamine hydrochloride (2 mg/kg) in the striatum between the two groups, whereas in the hippocampus, the maximum and subsequent increase of acetylcholine from the baseline by scopolamine injection was significantly lower in the choline-deficient group than in the control. From the results of our study, we speculate that long-term dietary restriction of choline can affect extra- and intracellular sources of substrates required for acetylcholine synthesis, and eventually limit the ability to release acetylcholine in the hippocampus. Reduced capacity to release acetylcholine in the hippocampus implies that the mechanism, maintaining acetylcholine synthesis on increased neuronal demand, may vary in discrete regions of the brain in response to dietary manipulation. The vulnerability of the mechanism in the hippocampus to dietary choline restriction is indicated by impaired mnemonic performance we observed.

  5. A Novel Hemp Seed Meal Protein Hydrolysate Reduces Oxidative Stress Factors in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Abraham T. Girgih

    2014-12-01

    Full Text Available This report shows the antioxidant effects of a hemp seed meal protein hydrolysate (HMH in spontaneously hypertensive rats (SHR. Defatted hemp seed meal was hydrolyzed consecutively with pepsin and pancreatin to yield HMH, which was incorporated into rat feed as a source of antioxidant peptides. Young (8-week old SHRs were divided into three groups (8 rats/group and fed diets that contained 0.0%, 0.5% or 1.0% (w/w HMH for eight weeks; half of the rats were sacrificed for blood collection. After a 4-week washout period, the remaining 20-week old SHRs were fed for an additional four weeks and sacrificed for blood collection. Plasma total antioxidant capacity (TAC and superoxide dismutase (SOD, catalase (CAT and total peroxides (TPx levels were determined. Results showed that plasma TAC, CAT and SOD levels decreased in the older 20-week old SHRs when compared to the young SHRs. The presence of HMH in the diets led to significant (p < 0.05 increases in plasma SOD and CAT levels in both young and adult SHR groups; these increases were accompanied by decreases in TPx levels. The results suggest that HMH contained antioxidant peptides that reduced the rate of lipid peroxidation in SHRs with enhanced antioxidant enzyme levels and total antioxidant capacity.

  6. Sepsis Patients Display a Reduced Capacity to Activate Nuclear Factor-κB in Multiple Cell Types

    NARCIS (Netherlands)

    Hoogendijk, Arie J.; Garcia-Laorden, M. Isabel; van Vught, Lonneke A.; Wiewel, Maryse A.; Belkasim-Bohoudi, Hakima; Duitman, Janwillem; Horn, Janneke; Schultz, Marcus J.; Scicluna, Brendon P.; van 't Veer, Cornelis; de Vos, Alex F.; van der Poll, Tom

    2017-01-01

    Sepsis is a complex clinical condition associated with high morbidity and mortality. A distinctive feature of sepsis is the reduced capacity of leukocytes to release proinflammatory cytokines in response to ex vivo stimulation. Cellular signaling events leading to immunosuppression in sepsis are not

  7. Escitalopram reduces increased hippocampal cytogenesis in a genetic rat depression model

    DEFF Research Database (Denmark)

    Petersén, Asa; Wörtwein, Gitta; Gruber, Susanne H M

    2008-01-01

    to stressors, but, so far, not in models of depression. Here we report that the number of BrdU positive cells in hippocampus was (1) significantly higher in a rat model of depression, the Flinders Sensitive Line (FSL) compared to control FRL, (2) increased in both FSL and FRL following maternal separation, (3......) reduced by escitalopram treatment in maternally separated animals to the level found in non-separated animals. These results argue against the prevailing hypothesis that adult cytogenesis is reduced in depression and that the common mechanism underlying antidepressant treatments is to increase adult...

  8. Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation.

    Science.gov (United States)

    Galvão, Marcella C; Chaves-Kirsten, Gabriela P; Queiroz-Hazarbassanov, Nicolle; Carvalho, Virgínia M; Bernardi, Maria M; Kirsten, Thiago B

    2015-01-01

    Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 μg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. We prenatally exposed Wistar rats to LPS (100 μg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. Our findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. A magnesium based phosphate binder reduces vascular calcification without affecting bone in chronic renal failure rats.

    Directory of Open Access Journals (Sweden)

    Ellen Neven

    Full Text Available The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF. In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover.

  10. Immunotoxicity of nucleic acid reduced BioProtein - a bacterial derived single cell protein - in Wistar rats

    DEFF Research Database (Denmark)

    Mølck, Anne-marie; Poulsen, Morten; Christensen, Hanne Risager

    2002-01-01

    , therefore, a nucleic acid reduced variant (NABP) has been developed by the manufacturer. The purpose of the present study was to establish the safety of NABP in a subchronic toxicity rat study. Groups of 10 male and 10 female Wistar rats were fed diets containing 0, 6, 12 or 24% NABP for 13 weeks. Feeding...

  11. Sauroxine reduces memory retention in rats and impairs hippocampal long-term potentiation generation.

    Science.gov (United States)

    Vallejo, Mariana; Carlini, Valeria; Gabach, Laura; Ortega, M G; L Cabrera, José; de Barioglio, Susana Rubiales; Pérez, Mariela; Agnese, Alicia M

    2017-07-01

    In the present paper it was investigated the role of sauroxine, an alkaloid of Phlegmariurus saururus, as a modulator of some types of learning and memory, considering the potential nootropic properties previously reported for the alkaloid extract and the main alkaloid sauroine. Sauroxine was isolated by means of an alkaline extraction, purified by several chromatographic techniques, and assayed in electrophysiological experiments on rat hippocampus slices, tending towards the elicitation of the long-term potentiation (LTP) phenomena. It was also studied the effects of intrahippocampal administration of sauroxine on memory retention in vivo using a Step-down test. Being the bio distribution of a drug an important parameter to be considered, the concentration of sauroxine in rat brain was determined by GLC-MS. Sauroxine blocked LTP generation at both doses used, 3.65 and 3.610 -2 μM. In the behavioral test, the animals injected with this alkaloid (3.6510 -3 nmol) exhibited a significant decrease on memory retention compared with control animals. It was also showed that sauroxine reached the brain (3.435μg/g tissue), after an intraperitoneal injection, displaying its ability to cross the blood-brain barrier. Thus, sauroxine demonstrated to exert an inhibition on these mnemonic phenomena. The effect here established for 1 is defeated by other constituents according to the excellent results obtained for P. saururus alkaloid extract as well as for the isolated alkaloid sauroine. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Tributyltin contributes in reducing the vascular reactivity to phenylephrine in isolated aortic rings from female rats.

    Science.gov (United States)

    Rodrigues, Samya Mere L; Ximenes, Carolina F; de Batista, Priscila R; Simões, Fabiana V; Coser, Pedro Henrique P; Sena, Gabriela C; Podratz, Priscila L; de Souza, Leticia N G; Vassallo, Dalton V; Graceli, Jones B; Stefanon, Ivanita

    2014-03-21

    Organotin compounds such as tributyltin (TBT) are used as antifouling paints by shipping companies. TBT inhibits the aromatase responsible for the transformation of testosterone into estrogen. Our hypothesis is that TBT modulates the vascular reactivity of female rats. Female Wistar rats were treated daily (Control; CONT) or TBT (100 ng/kg) for 15 days. Rings from thoracic aortas were incubated with phenylephrine (PHE, 10(-10)-10(-4) M) in the presence and absence of endothelium, and in the presence of N(G)-Nitro-L-Arginine Methyl Ester (L-NAME), tetraethylammonium (TEA) and apocynin. TBT decreased plasma levels of estrogen and the vascular response to PHE. In the TBT group, the vascular reactivity was increased in the absence of endothelium, L-NAME and TEA. The decrease in PHE reactivity during incubation with apocynin was more evident in the TBT group. The sensitivity to acetylcholine (ACh) and sodium nitroprusside (SNP) was reduced in the TBT group. TBT increased collagen, reduced α1-smooth muscle actin. Female rats treated with TBT for 15 days showed morphology alteration of the aorta and decreased their vascular reactivity, probably due to mechanisms dependent on nitric oxide (NO) bioavailability, K(+) channels and an increase in oxidative stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats.

    Science.gov (United States)

    Dworak, Markus; Kim, Tae; Mccarley, Robert W; Basheer, Radhika

    2017-06-01

    Sleep has been postulated to promote brain energy restoration. It is as yet unknown if increasing the energy availability within the brain reduces sleep need. The guanidine amino acid creatine (Cr) is a well-known energy booster in cellular energy homeostasis. Oral Cr-monohydrate supplementation (CS) increases exercise performance and has been shown to have substantial effects on cognitive performance, neuroprotection and circadian rhythms. The effect of CS on cellular high-energy molecules and sleep-wake behaviour is unclear. Here, we examined the sleep-wake behaviour and brain energy metabolism before and after 4-week-long oral administration of CS in the rat. CS decreased total sleep time and non-rapid eye movement (NREM) sleep significantly during the light (inactive) but not during the dark (active) period. NREM sleep and NREM delta activity were decreased significantly in CS rats after 6 h of sleep deprivation. Biochemical analysis of brain energy metabolites showed a tendency to increase in phosphocreatine after CS, while cellular adenosine triphosphate (ATP) level decreased. Microdialysis analysis showed that the sleep deprivation-induced increase in extracellular adenosine was attenuated after CS. These results suggest that CS reduces sleep need and homeostatic sleep pressure in rats, thereby indicating its potential in the treatment of sleep-related disorders. © 2017 European Sleep Research Society.

  14. Atorvastatin reduces cardiac and adipose tissue inflammation in rats with metabolic syndrome.

    Science.gov (United States)

    Yamada, Yuichiro; Takeuchi, Shino; Yoneda, Mamoru; Ito, Shogo; Sano, Yusuke; Nagasawa, Kai; Matsuura, Natsumi; Uchinaka, Ayako; Murohara, Toyoaki; Nagata, Kohzo

    2017-08-01

    Statins are strong inhibitors of cholesterol biosynthesis and help to prevent cardiovascular disease. They also exert additional pleiotropic effects that include an anti-inflammatory action and are independent of cholesterol, but the molecular mechanisms underlying these additional effects have remained unclear. We have now examined the effects of atorvastatin on cardiac and adipose tissue inflammation in DahlS.Z-Lepr fa /Lepr fa (DS/obese) rats, which we previously established as a model of metabolic syndrome (MetS). DS/obese rats were treated with atorvastatin (6 or 20mgkg -1 day -1 ) from 9 to 13weeks of age. Atorvastatin ameliorated cardiac fibrosis, diastolic dysfunction, oxidative stress, and inflammation as well as adipose tissue inflammation in these animals at both doses. The high dose of atorvastatin reduced adipocyte hypertrophy to a greater extent than did the low dose. Atorvastatin inhibited the up-regulation of peroxisome proliferator-activated receptor γ gene expression in adipose tissue as well as decreased the serum adiponectin concentration in DS/obese rats. It also activated AMP-activated protein kinase (AMPK) as well as inactivated nuclear factor-κB (NF-κB) in the heart of these animals. The down-regulation of AMPK and NF-κB activities in adipose tissue of DS/obese rats was attenuated and further enhanced, respectively, by atorvastatin treatment. The present results suggest that the anti-inflammatory effects of atorvastatin on the heart and adipose tissue are attributable at least partly to increased AMPK activity and decreased NF-κB activity in this rat model of MetS. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Helichrysum and Grapefruit Extracts Boost Weight Loss in Overweight Rats Reducing Inflammation.

    Science.gov (United States)

    de la Garza, Ana Laura; Etxeberria, Usune; Haslberger, Alexander; Aumueller, Eva; Martínez, J Alfredo; Milagro, Fermín I

    2015-08-01

    Obesity is characterized by an increased production of inflammatory markers. High levels of circulating free fatty acids and chronic inflammation lead to increased oxidative stress, contributing to the development of insulin resistance (IR). Recent studies have focused on the potential use of flavonoids for obesity management due to their antioxidant and anti-inflammatory properties. This study was designed to investigate the antioxidant and anti-inflammatory effects of helichrysum and grapefruit extracts in overweight insulin-resistant rats. Thirty-eight male Wistar rats were randomly distributed in two groups: control group (n=8) and high-fat sucrose (HFS) group (n=30). After 22 days of ad libitum water and food access, the rats fed HFS diet changed to standard diet and were reassigned into three groups (n=10 each group): nonsupplemented, helichrysum extract (2 g/kg bw), and grapefruit extract (1 g/kg bw) administered for 5 weeks. Rats supplemented with both extracts gained less body weight during the 5-week period of treatment, showed lower serum insulin levels and liver TBARS levels. Leptin/adiponectin ratio, as an indicator of IR, was lower in both extract-administered groups. These results were accompanied by a reduction in TNFα gene expression in epididymal adipose tissue and intestinal mucosa, and TLR2 expression in intestinal mucosa. Helichrysum and grapefruit extracts might be used as complement hypocaloric diets in weight loss treatment. Both extracts helped to reduce weight gain, hyperinsulinemia, and IR, improved inflammation markers, and decreased the HFS diet-induced oxidative stress in insulin-resistant rats.

  16. Correlation of catecholamine levels in the bed nucleus of the stria terminalis and reduced sexual behavior in middle-aged male rats.

    Science.gov (United States)

    Chen, Joyce C; Tsai, Houng-Wei; Yeh, Kuei-Ying; Tai, Mei-Yun; Tsai, Yuan-Feen

    2008-07-01

    The correlation between dopamine (DA) and norepinephrine (NE) levels in the bed nucleus of the stria terminalis (BNST) and male sexual behavior was examined in middle-aged rats. Male rats (18-19 months) were divided into: (a) Group MIE, consisting of rats showing mounts, intromissions, and ejaculations; (b) Group MI, composed of rats showing mounts and intromissions, but no ejaculation; and (c) Group NC, consisting of noncopulators. Young adult rats (4-5 months) displaying complete copulatory behavior were used as the control. Tissue levels of DA, NE, and DA metabolites in the BNST were measured by high-pressure liquid chromatography. DA, but not NE, levels in MIE rats were significantly lower than those in young controls. DA and NE levels in MIE rats were significantly higher than those in NC rats. These results suggest that DA and NE in the BNST might play an important role in the control of male sexual behavior in middle-aged rats.

  17. Administration of dried Aloe vera gel powder reduced body fat mass in diet-induced obesity (DIO) rats.

    Science.gov (United States)

    Misawa, Eriko; Tanaka, Miyuki; Nabeshima, Kazumi; Nomaguchi, Kouji; Yamada, Muneo; Toida, Tomohiro; Iwatsuki, Keiji

    2012-01-01

    The aim of the present study was to investigate the anti-obesity effects of Aloe vera gel administration in male Sprague-Dawley (SD) rats with diet-induced obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal% fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period. Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body weights (g) and body fat (%) of HFD fed rats were significantly higher than those of StdD-fed rats. Although a modest decrease of body weight (g) was observed with the administration of dried Aloe vera gel powder, both subcutaneous and visceral fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel-treated rats. Serum lipid parameters elevated by HFD were also improved by the Aloe vera gel treatment. The oxygen consumption (VO(2)), an index of energy expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats. Administration of Aloe vera gel reversed the change in VO(2) in the HFD-fed rats. These results suggest that intake of Aloe vera gel reduced body fat accumulation, in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial for the prevention and improvement of diet-induced obesity.

  18. Prepubertal exposure to cow's milk reduces susceptibility to carcinogen-induced mammary tumorigenesis in rats

    DEFF Research Database (Denmark)

    Nielsen, Tina Skau; Khan, Galam; Davis, Jennifer

    2011-01-01

    Cow's milk contains high levels of estrogens, progesterone and insulin-like growth factor 1 (IGF-1), all of which are associated with breast cancer. We investigated whether prepubertal milk exposure affects mammary gland development and carcinogenesis in rats. Sprague-Dawley rats were given either...... whole milk or tap water to drink from postnatal day (PND) 14 to PND 35, and thereafter normal tap water. Mammary tumorigenesis was induced by administering 7,12-dimethylbenz[a]anthracene on PND 50. Milk exposure increased circulating E2 levels on PND 25 by 10-fold (p ... opening, which marks puberty onset, by 2.5 days (p milk before puberty exhibited reduced carcinogen-induced mammary carcinogenesis; that is, their tumor latency was longer (p

  19. Swimming reduces the severity of physical and psychological dependence and voluntary morphine consumption in morphine dependent rats.

    Science.gov (United States)

    Fadaei, Atefeh; Gorji, Hossein Miladi; Hosseini, Shahrokh Makvand

    2015-01-15

    Previous studies have indicated that voluntary exercise decreases the severity of the anxiogenic-like behaviors in both morphine-dependent and withdrawn rats. This study examined the effects of regular swimming exercise during the development of dependency and spontaneous morphine withdrawal on the anxiety-depression profile and voluntary morphine consumption in morphine dependent rats. The rats were chronically treated with bi-daily doses (10 mg/kg, at 12h intervals) of morphine over a period of 14 days. The exercising rats were allowed to swim (45 min/d, five days per a week, for 14 or 21 days) during the development of morphine dependence and withdrawal. Then, rats were tested for the severity of morphine dependence, the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice paradigm in animal models of craving. The results showed that withdrawal signs were decreased in swimmer morphine dependent rats than sedentary rats (Pmorphine-dependent and withdrawn rats exhibited an increase in EPM open arm time and entries (Pmorphine was less in the swimmer morphine-withdrawn rats than the sedentary groups during four periods of the intake of drug (Pmorphine dependence and voluntary morphine consumption with reducing anxiety and depression in morphine-dependent and withdrawn rats. Thus, swimming exercise may be a potential method to ameliorate some of the deleterious behavioral consequences of morphine dependence. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Red algae (Gelidium amansii reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide

    Directory of Open Access Journals (Sweden)

    Tsung-Han Yang

    2015-12-01

    Full Text Available Gelidium amansii (GA is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1 rats without diabetes fed a high-fat diet (control group; (2 rats with diabetes fed a high-fat diet; (3 rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4 rats with diabetes fed a high-fat diet and GA. The experimental diet and drinking water were available ad libitum for 11 weeks. After the 11-week feeding study, plasma glucose, triglyceride, and cholesterol concentrations were lower in rats with diabetes fed the GA diet than in animals with diabetes fed the control diet. In addition, cholesterol and triglyceride excretion were significantly higher in rats with diabetes fed the GA diet. Moreover, GA feeding induced lipolysis in both paraepididymal and perirenal adipose tissues. Adipose tissue (paraepididymal and perirenal weight and triglyceride contents were lower after GA treatment. Plasma adipocytokines including tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor-1 were reduced by GA feeding in rats with diabetes. The results of the current study suggest that GA feeding may regulate plasma glucose and lipid levels and prevent adipose tissue accumulation in rats with diabetes.

  1. Red algae (Gelidium amansii) reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide.

    Science.gov (United States)

    Yang, Tsung-Han; Yao, Hsien-Tsung; Chiang, Meng-Tsan

    2015-12-01

    Gelidium amansii (GA) is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1) rats without diabetes fed a high-fat diet (control group); (2) rats with diabetes fed a high-fat diet; (3) rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4) rats with diabetes fed a high-fat diet and GA. The experimental diet and drinking water were available ad libitum for 11 weeks. After the 11-week feeding study, plasma glucose, triglyceride, and cholesterol concentrations were lower in rats with diabetes fed the GA diet than in animals with diabetes fed the control diet. In addition, cholesterol and triglyceride excretion were significantly higher in rats with diabetes fed the GA diet. Moreover, GA feeding induced lipolysis in both paraepididymal and perirenal adipose tissues. Adipose tissue (paraepididymal and perirenal) weight and triglyceride contents were lower after GA treatment. Plasma adipocytokines including tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor-1 were reduced by GA feeding in rats with diabetes. The results of the current study suggest that GA feeding may regulate plasma glucose and lipid levels and prevent adipose tissue accumulation in rats with diabetes. Copyright © 2015. Published by Elsevier B.V.

  2. Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats.

    Science.gov (United States)

    Philogene-Khalid, Helene L; Hicks, Callum; Reitz, Allen B; Liu-Chen, Lee-Yuan; Rawls, Scott M

    2017-09-01

    The neuropharmacological profile of the synthetic cathinone mephedrone (MEPH) is influenced by stereochemistry. Both MEPH enantiomers are monoamine transporter substrates, but R-MEPH is primarily responsible for rewarding effects of MEPH as it produces greater locomotor activation and intracranial self-stimulation than S-MEPH. S-MEPH is a 50-fold more potent 5-HT releaser than R-MEPH and does not place preference in rats. MEPH is also structurally similar to the cathinone derivative bupropion, an antidepressant and smoking cessation medication, suggesting MEPH has therapeutic and addictive properties. We tested the hypothesis that S-MEPH reduces anxiety- and depression-like behaviors in rats withdrawn from chronic cocaine or methylenedioxypyrovalerone (MDPV) using the elevated plus maze (EPM) and forced swim test (FST), respectively. Rats were tested 48-h after a binge-like paradigm (3×/day for 10days in 1-h intervals) of cocaine (10mg/kg), MDPV (1mg/kg) or saline. In vitro studies assessed the receptor binding and activity of S-MEPH. Rats withdrawn from chronic cocaine or MDPV displayed an increase in anxiety- and depression-like behaviors that was antagonized by treatment with S-MEPH (10, 30mg/kg). S-MEPH displayed affinity, but not agonist activity, for 5-HT 2 receptors (2A-2C) and showed negligible affinity for dopaminergic, adrenergic and nicotinic receptors. S-MEPH attenuated withdrawal behaviors following chronic cocaine or MDPV, perhaps through 5-HT release and/or 5-HT 2 receptor interactions. The present data suggest S-MEPH may be a possible structural and pharmacological template to develop maintenance therapy for acute anxiety and depression during early withdrawal from psychostimulant abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae.

    Science.gov (United States)

    Pham, Toan; Nisbet, Linley; Taberner, Andrew; Loiselle, Denis; Han, June-Chiew

    2018-04-01

    Pulmonary arterial hypertension (PAH) triggers right ventricle (RV) hypertrophy and left ventricle (LV) atrophy, which progressively leads to heart failure. We designed experiments under conditions mimicking those encountered by the heart in vivo that allowed us to investigate whether consequent structural and functional remodelling of the ventricles affects their respective energy efficiencies. We found that peak work output was lower in RV trabeculae from PAH rats due to reduced extent and velocity of shortening. However, their suprabasal enthalpy was unaffected due to increased activation heat, resulting in reduced suprabasal efficiency. There was no effect of PAH on LV suprabasal efficiency. We conclude that the mechanism underlying the reduced energy efficiency of hypertrophied RV tissues is attributable to the increased energy cost of Ca 2+ cycling, whereas atrophied LV tissues still maintain normal mechano-energetic performance. Pulmonary arterial hypertension (PAH) greatly increases the afterload on the right ventricle (RV), triggering RV hypertrophy, which progressively leads to RV failure. In contrast, the disease reduces the passive filling pressure of the left ventricle (LV), resulting in LV atrophy. We investigated whether these distinct structural and functional consequences to the ventricles affect their respective energy efficiencies. We studied trabeculae isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and their respective Control groups. Trabeculae were mounted in a calorimeter at 37°C. While contracting at 5 Hz, they were subjected to stress-length work-loops over a wide range of afterloads. They were subsequently required to undergo a series of isometric contractions at various muscle lengths. In both protocols, stress production, length change and suprabasal heat output were simultaneously measured. We found that RV trabeculae from PAH rats generated higher activation heat, but developed normal active stress. Their

  4. GDNF family ligands display distinct action profiles on cultured GABAergic and serotonergic neurons of rat ventral mesencephalon

    DEFF Research Database (Denmark)

    Ducray, Angélique; Krebs, Sandra H:; Schaller, Benoft

    2006-01-01

    the effects of GFLs on other neuronal populations in the VM is essential for their potential application as therapeutic molecules for Parkinson's disease. Hence, in a comparative study, we investigated the effects of GFLs on cell densities and morphological differentiation of gamma-aminobutyric acid......Glial-cell-line-derived neurotrophic factor (GDNF), neurturin (NRTN), artemin (ARTN) and persephin (PSPN), known as the GDNF family ligands (GFLs), influence the development, survival and differentiation of cultured dopaminergic neurons from ventral mesencephalon (VM). Detailed knowledge about......-immunoreactive (GABA-ir) and serotonin-ir (5-HT-ir) neurons in primary cultures of E14 rat VM. We observed that all GFLs [10 ng/ml] significantly increased GABA-ir cell densities (1.6-fold) as well as neurite length/neuron. However, only GDNF significantly increased the number of primary neurites/neuron, and none...

  5. Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem cell-mediated liver regeneration

    DEFF Research Database (Denmark)

    Jelnes, Peter; Santoni-Rugiu, Eric; Rasmussen, Morten

    2007-01-01

    The experimental protocols used in the investigation of stem cell-mediated liver regeneration in rodents are characterized by activation of the hepatic stem cell compartment in the canals of Hering followed by transit amplification of oval cells and their subsequent differentiation along hepatic...... the molecular phenotypes of oval cells in several of the most commonly used protocols of stem cell-mediated liver regeneration-namely, treatment with 2-acetylaminofluorene and partial (70%) hepatectomy (AAF/PHx); a choline-deficient, ethionine-supplemented (CDE) diet; a 3,5-diethoxycarbonyl-1,4-dihydro...... remarkable phenotypic discrepancies exhibited by oval cells in stem cell-mediated liver regeneration between rats and mice and underline the importance of careful extrapolation between individual species....

  6. Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection.

    Science.gov (United States)

    Lu, Yang; Yang, Yang; He, Xin; Dong, Shangwen; Wang, Wanhua; Wang, Donghao; Zhang, Peng

    2017-10-01

    Esmolol is a highly selective beta 1 receptor blocker with various effects such as slowing heart rate, lowering blood pressure and reducing myocardial oxygen consumption. However, few studies have reported the use of beta blockers in sepsis with multiple organ dysfunctions. This study aimed to investigate the effects of esmolol on reducing apoptosis and inflammation in early sepsis rats with abdominal infection. Rats were randomly divided into sham operation group, sepsis group, antibiotic group, Esmolol + antibiotic group with low, median and high dose Esmolol (L group, M group and H group). Values between two or more groups were compared by independent t-tests. In the liver and kidney, we found inflammatory infiltration in sepsis group while pathological aspects reduced in L, M and H groups. Bcl-2 mRNA and protein levels increased while Bax mRNA and protein levels decreased in the liver and kidney of L, M and H groups. Serum IL-6, HMGB-1 and TNF-α levels decreased but IL-10 level increased in L, M and H groups, compared to sepsis group. Compared to sepsis and antibiotic groups, the levels of myocardial enzymes were lower in L, M and H groups. The administration of esmolol in early sepsis may reduce inflammation, inhibit apoptosis and protect key organs. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

    Science.gov (United States)

    Zonta, Yohan Ricci; Martinez, Marcelo; Camargo, Isabel Cristina C.; Domeniconi, Raquel F.; Lupi Júnior, Luiz Antonio; Pinheiro, Patricia Fernanda F.; Reiter, Russel J.; Martinez, Francisco Eduardo; Chuffa, Luiz Gustavo A.

    2017-01-01

    Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received intraperitoneal injections of melatonin (200 µg/100 g body weight/day) for 60 days. Melatonin-treated animals showed a significant reduction in OC size and microvessel density. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1 was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFβ1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and, notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC in an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy. PMID:28398226

  8. Silymarin ameliorates fructose induced insulin resistance syndrome by reducing de novo hepatic lipogenesis in the rat.

    Science.gov (United States)

    Prakash, Prem; Singh, Vishal; Jain, Manish; Rana, Minakshi; Khanna, Vivek; Barthwal, Manoj Kumar; Dikshit, Madhu

    2014-03-15

    High dietary fructose causes insulin resistance syndrome (IRS), primarily due to simultaneous induction of genes involved in glucose, lipid and mitochondrial oxidative metabolism. The present study evaluates effect of a hepatoprotective agent, silymarin (SYM) on fructose-induced metabolic abnormalities in the rat and also assessed the associated thrombotic complications. Wistar rats were kept on high fructose (HFr) diet throughout the 12-week study duration (9 weeks of HFr feeding and subsequently 3 weeks of HFr plus SYM oral administration [once daily]). SYM treatment significantly reduced the HFr diet-induced increase expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α/β, peroxisome proliferator-activated receptor (PPAR)-α, forkhead box protein O1 (FOXO1), sterol regulatory element binding protein (SREBP)-1c, liver X receptor (LXR)-β, fatty acid synthase (FAS) and PPARγ genes in rat liver. SYM also reduced HFr diet mediated increase in plasma triglycerides (TG), non-esterified fatty acids (NEFA), uric acid, malondialdehyde (MDA), total nitrite and pro-inflammatory cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-gamma [IFN-γ] and tumor necrosis factor [TNF]) levels. Moreover, SYM ameliorated HFr diet induced reduction in glucose utilization and endothelial dysfunction. Additionally, SYM significantly reduced platelet activation (adhesion and aggregation), prolonged ferric chloride-induced blood vessel occlusion time and protected against exacerbated myocardial ischemia reperfusion (MI-RP) injury. SYM treatment prevented HFr induced mRNA expression of hepatic PGC-1α/β and also its target transcription factors which was accompanied with recovery in insulin sensitivity and reduced propensity towards thrombotic complications and aggravated MI-RP injury. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage.

    Science.gov (United States)

    Quek, Hazel; Luff, John; Cheung, KaGeen; Kozlov, Sergei; Gatei, Magtouf; Lee, C Soon; Bellingham, Mark C; Noakes, Peter G; Lim, Yi Chieh; Barnett, Nigel L; Dingwall, Steven; Wolvetang, Ernst; Mashimo, Tomoji; Roberts, Tara L; Lavin, Martin F

    2017-04-01

    Mutations in the ataxia-telangiectasia (A-T)-mutated ( ATM ) gene give rise to the human genetic disorder A-T, characterized by immunodeficiency, cancer predisposition, and neurodegeneration. Whereas a series of animal models recapitulate much of the A-T phenotype, they fail to present with ataxia or neurodegeneration. We describe here the generation of an Atm missense mutant [amino acid change of leucine (L) to proline (P) at position 2262 (L2262P)] rat by intracytoplasmic injection (ICSI) of mutant sperm into oocytes. Atm -mutant rats ( Atm L2262P/L2262P ) expressed low levels of ATM protein, suggesting a destabilizing effect of the mutation, and had a significantly reduced lifespan compared with Atm +/+ Whereas these rats did not show cerebellar atrophy, they succumbed to hind-limb paralysis (45%), and the remainder developed tumors. Closer examination revealed the presence of both dsDNA and ssDNA in the cytoplasm of cells in the hippocampus, cerebellum, and spinal cord of Atm L2262P/L2262P rats. Significantly increased levels of IFN-β and IL-1β in all 3 tissues were indicative of DNA damage induction of the type 1 IFN response. This was further supported by NF-κB activation, as evidenced by p65 phosphorylation (P65) and translocation to the nucleus in the spinal cord and parahippocampus. Other evidence of neuroinflammation in the brain and spinal cord was the loss of motor neurons and the presence of increased activation of microglia. These data provide support for a proinflammatory phenotype that is manifested in the Atm mutant rat as hind-limb paralysis. This mutant represents a useful model to investigate the importance of neuroinflammation in A-T. © Society for Leukocyte Biology.

  10. Gestational or acute restraint in adulthood reduces levels of 5α-reduced testosterone metabolites in the hippocampus and produces behavioral inhibition of adult male rats

    Directory of Open Access Journals (Sweden)

    Alicia A Walf

    2012-12-01

    Full Text Available Stressors, during early life or adulthood, can alter steroid-sensitive behaviors, such as exploration, anxiety, and/or cognitive processes. We investigated if exposure to acute stressors in adulthood may alter behavioral and neuroendocrine responses of male rats that were exposed to gestational stress or not. We hypothesized that rats exposed to gestational and acute stress may show behavioral inhibition, increased corticosterone, and altered androgen levels in the hippocampus. Subjects were adult, male offspring of rat dams that were restrained daily on gestational days 14-20, or did not experience this manipulation. Immediately before testing, rats were restraint-stressed for 20 minutes or not. During week 1, rats were tested in a battery of tasks, including the open field, elevated plus maze, social interaction, tailflick, pawlick, and defensive burying tasks. During week 2, rats were trained and tested 24 hours later in the inhibitory avoidance task. Plasma corticosterone and androgen levels, and hippocampal androgen levels, were measured in all subjects. Gestational and acute restraint stress increased plasma levels of corticosterone, and reduced levels of testosterone’s 5α-reduced metabolites, dihydrotestosterone and 3α-androstanediol, but not the aromatized metabolite, estradiol, in plasma or the hippocampus. Gestational and acute restraint stress reduced central entries made in the open field, and latencies to enter the shock-associated side of the inhibitory avoidance chamber during testing. Gestational stress reduced time spent interacting with a conspecific. These data suggest that gestational and acute restraint stress can have actions to produce behavioral inhibition coincident with increased corticosterone and decreased 5α-reduced androgens of adult male rats. Thus, gestational stress altered neural circuits involved in the neuroendocrine response to acute stress in early adulthood.

  11. Adolescents with clinical type 1 diabetes display reduced red blood cell glucose transporter isoform 1 (GLUT1).

    Science.gov (United States)

    Garg, Meena; Thamotharan, Manikkavasagar; Becker, Dorothy J; Devaskar, Sherin U

    2014-11-01

    Type 1 diabetic (T1D) adolescent children on insulin therapy suffer episodes of both hyper- and hypoglycemic episodes. Glucose transporter isoform GLUT1 expressed in blood-brain barrier (BBB) and red blood cells (RBC) compensates for perturbed circulating glucose toward protecting the supply to brain and RBCs. We hypothesized that RBC-GLUT1 concentration, as a surrogate for BBB-GLUT1, is altered in T1D children. To test this hypothesis, we measured RBC-GLUT1 by enzyme-linked immunosorbent assay (ELISA) in T1D children (n = 72; mean age 15.3 ± 0.2 yr) and control children (CON; n = 11; mean age 15.6 ± 0.9 yr) after 12 h of euglycemia and during a hyperinsulinemic-hypoglycemic clamp with a nadir blood glucose of ~3.3 mmol/L for 90 min (clamp I) or ~3 mmol/L for 45 min (clamp II). Reduced baseline RBC-GLUT1 was observed in T1D (2.4 ± 0.17 ng/ng membrane protein); vs. CON (4.2 ± 0.61 ng/ng protein) (p < 0.0001). Additionally, baseline RBC-GLUT1 in T1D negatively correlated with hemoglobin A1c (HbA1c) (R = -0.23, p < 0.05) but not in CON (R = 0.06, p < 0.9). Acute decline in serum glucose to 3.3 mmol/L (90 min) or 3 mmol/L (45 min) did not change baseline RBC-GLUT1 in T1D or CON children. We conclude that reduced RBC-GLUT1 encountered in T1D, with no ability to compensate by increasing during acute hypoglycemia over the durations examined, may demonstrate a vulnerability of impaired RBC glucose transport (serving as a surrogate for BBB), especially in those with the worst control. We speculate that this may contribute to the perturbed cognition seen in T1D adolescents. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Calpain inhibition reduces NMDA receptor rundown in rat substantia nigra dopamine neurons.

    Science.gov (United States)

    Zhao, Jerry; Baudry, Michel; Jones, Susan

    2018-05-04

    Repeated activation of N-Methyl-d-aspartate receptors (NMDARs) causes a Ca 2+ -dependent reduction in NMDAR-mediated current in dopamine (DA) neurons of the substantia nigra pars compacta (SNc) in one week old rats; however, a Ca 2+ -dependent regulatory protein has not been identified. The role of the Ca 2+ -dependent cysteine protease, calpain, in mediating NMDAR current rundown was investigated. In brain slices from rats aged postnatal day 7-9 ('P7'), bath application of either of the membrane permeable calpain inhibitors, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN, 20 μM) or MDL-28170 (30 μM) significantly reduced whole-cell NMDAR current rundown. To investigate the role of the calpain-2 isoform, the membrane permeable calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I, 200 nM), was applied; C2I application significantly reduced whole cell NMDAR current rundown. Interestingly, ALLN but not C2I significantly reduced rundown of NMDA-EPSCs. These results suggest the calpain-2 isoform mediates Ca 2+ -dependent regulation of extrasynaptic NMDAR current in the first postnatal week, while calpain-1 might mediate rundown of synaptic NMDAR currents. One week later in postnatal development, at P12-P16 ('P14'), there was significantly less rundown in SNc-DA neurons, and no significant effect on rundown of either Ca 2+ chelation or treatment with the calpain inhibitor, ALLN, suggesting that the rundown observed in SNc-DA neurons from two week-old rats might be Ca 2+ -independent. In conclusion, Ca 2+ -dependent rundown of extrasynaptic NMDAR currents in SNc DA neurons involves calpain-2 activation, but Ca 2+ - and calpain-2-dependent NMDAR current rundown is developmentally regulated. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Fenofibrate--a lipid-lowering drug--reduces voluntary alcohol drinking in rats.

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    Karahanian, Eduardo; Quintanilla, Maria Elena; Fernandez, Katia; Israel, Yedy

    2014-11-01

    The administration of disulfiram raises blood acetaldehyde levels when ethanol is ingested, leading to an aversion to alcohol. This study was aimed at assessing the effect of fenofibrate on voluntary ethanol ingestion in rats. Fenofibrate reduces blood triglyceride levels by increasing fatty acid oxidation by liver peroxisomes, along with an increase in the activity of catalase, which can oxidize ethanol to acetaldehyde. UChB drinker rats were allowed to consume alcohol 10% v/v freely for 60 days, until consumption stabilized at around 7 g ethanol/kg/24 h. About 1-1.2 g ethanol/kg of this intake is consumed in the first 2 h of darkness of the circadian cycle. Fenofibrate subsequently administered (50 mg/kg/day by mouth [p.o.]) for 14 days led to a 60-70% (p intake was determined within the first 2 h of darkness, the reduction was 85-90% (p chronically allowed access to ethanol and subsequently treated with fenofibrate, would a) increase liver catalase activity, and b) increase blood acetaldehyde levels after a 24-h ethanol deprivation and the subsequent administration of 1 g ethanol/kg. The oral administration of 1 g ethanol/kg produced a rapid increase in blood (arterial) acetaldehyde in fenofibrate-treated animals versus controls also administered 1 g/kg ethanol (70 μM vs. 7 μM; p alcohol dehydrogenase and aldehyde dehydrogenase) remained unchanged. No liver damage was induced, as measured by serum glutamic-pyruvic transaminase (GPT) activity. The effect of fenofibrate in reducing alcohol intake was fully reversible. Overall, in rats allowed chronic ethanol intake, by mouth (p.o.), fenofibrate administration increased liver catalase activity and reduced voluntary ethanol intake. The administration of 1 g ethanol/kg (p.o.) to these animals increased blood acetaldehyde levels in fenofibrate-treated animals, suggesting the possible basis for the reduction in ethanol intake. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Local anaesthetic refinement of pentobarbital euthanasia reduces abdominal writhing without affecting immunohistochemical endpoints in rats.

    Science.gov (United States)

    Khoo, Shaun Y-S; Lay, Belinda P P; Joya, Josephine; McNally, Gavan P

    2018-04-01

    Sodium pentobarbital is a commonly used agent for euthanizing laboratory rats, however its high pH can cause abdominal discomfort after intraperitoneal injection. Previous studies suggest that the addition of a local anaesthetic may alleviate this discomfort, but the practice has not been widely adopted. We examined the effect of combining lidocaine with pentobarbital on abdominal writhing, defecation, ultrasonic vocalizations, the rat grimace scale and immunohistochemical staining for c-Fos in the nucleus accumbens and basolateral amygdala of the brain. We also compared the amount of abdominal writhing following intraperitoneal administration of pentobarbital-lidocaine with that of pentobarbital-bupivacaine. Our results show that lidocaine reduces abdominal writhing and defecation without affecting immunohistochemistry for c-Fos or latency to loss of posture. However, scores on the rat grimace scale were low in both situations and almost no ultrasonic vocalizations were recorded. Additionally, we found that the amount of abdominal writhing was not significantly different when bupivacaine was used rather than lidocaine. Our results suggest that pentobarbital-induced euthanasia can be refined with the addition of lidocaine or other local anaesthetics.

  15. The Edible Brown Seaweed Ecklonia cava Reduces Hypersensitivity in Postoperative and Neuropathic Pain Models in Rats

    Directory of Open Access Journals (Sweden)

    Jae Goo Kim

    2014-06-01

    Full Text Available The current study was designed to investigate whether edible brown seaweed Ecklonia cava extracts exhibits analgesic effects in plantar incision and spared nerve injury (SNI rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT and thermal hypersensitivity tests measured by von Frey filaments and a hot/cold plate analgesia meter. Pain-related behavior was also determined through analysis of ultrasonic vocalization. The results of experiments showed MWT values of the group that was treated with E. cava extracts by 300 mg/kg significantly increased; on the contrary, number of ultrasonic distress vocalization of the treated group was reduced at 6 h and 24 h after plantar incision operation (62.8%, p < 0.05. Moreover, E. cava 300 mg/kg treated group increased the paw withdrawal latency in hot-and cold-plate tests in the plantar incision rats. After 15 days of continuous treatment with E. cava extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity response by MWT compared with the control group. In conclusion, these results suggest that E. cava extracts have potential analgesic effects in the case of postoperative pain and neuropathic pain in rats.

  16. FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis

    Science.gov (United States)

    Verbeke, Len; Mannaerts, Inge; Schierwagen, Robert; Govaere, Olivier; Klein, Sabine; Vander Elst, Ingrid; Windmolders, Petra; Farre, Ricard; Wenes, Mathias; Mazzone, Massimiliano; Nevens, Frederik; van Grunsven, Leo A.; Trebicka, Jonel; Laleman, Wim

    2016-01-01

    Hepatic inflammation drives hepatic stellate cells (HSC), resulting in liver fibrosis. The Farnesoid-X receptor (FXR) antagonizes inflammation through NF-κB inhibition. We investigated preventive and therapeutic effects of FXR agonist obeticholic acid (OCA) on hepatic inflammation and fibrosis in toxic cirrhotic rats. Cirrhosis was induced by thioacetamide (TAA) intoxication. OCA was given during or after intoxication with vehicle-treated rats as controls. At sacrifice, fibrosis, hemodynamic and biochemical parameters were assessed. HSC activation, cell turn-over, hepatic NF-κB activation, pro-inflammatory and pro-fibrotic cytokines were determined. The effect of OCA was further evaluated in isolated HSC, Kupffer cells, hepatocytes and liver sinusoidal endothelial cells (LSEC). OCA decreased hepatic inflammation and fibrogenesis during TAA-administration and reversed fibrosis in established cirrhosis. Portal pressure decreased through reduced intrahepatic vascular resistance. This was paralleled by decreased expression of pro-fibrotic cytokines (transforming growth-factor β, connective tissue growth factor, platelet-derived growth factor β-receptor) as well as markers of hepatic cell turn-over, by blunting effects of pro-inflammatory cytokines (e.g. monocyte chemo-attractant protein-1). In vitro, OCA inhibited both LSEC and Kupffer cell activation; while HSC remained unaffected. This related to NF-κB inhibition via up-regulated IκBα. In conclusion, OCA inhibits hepatic inflammation in toxic cirrhotic rats resulting in decreased HSC activation and fibrosis. PMID:27634375

  17. Aversion learning can reduce meal size without taste avoidance in rats.

    Science.gov (United States)

    Tracy, Andrea L; Schurdak, Jennifer D; Chambers, James B; Benoit, Stephen C

    2016-03-01

    Nausea and aversive food responses are commonly reported following bariatric surgery, along with post-surgical reduction in meal size. This study investigates whether a meal size limit can be conditioned by associating large meals with aversive outcomes. In rats, the intake of meals exceeding a pre-defined size threshold was paired with lithium chloride-induced gastric illness, and the effects on self-determined food intakes and body weight were measured. Rats given LiCl contingent on the intake of a large meal learned to reliably reduce intake below this meal size threshold, while post-meal saline or LiCl before meals did not change meal size. It was further demonstrated that this is not a conditioned taste aversion and that this effect transferred to foods not explicitly trained. Finally, when rats received LiCl following all large meals, the number of small meals increased, but total food intake and body weight decreased. While further work is needed, this is the first demonstration that meal size may be conditioned, using an aversion procedure, to remain under a target threshold and that this effect is distinct from taste avoidance. Corresponding reduction in food intake and body weight suggests that this phenomenon may have implications for developing weight loss strategies and understanding the efficacy of bariatric surgery. © 2016 The Obesity Society.

  18. Reduced bioavailability of cyclosporine A in rats by mung bean seed coat extract

    Directory of Open Access Journals (Sweden)

    Xiping Li

    2014-09-01

    Full Text Available Mung bean seed coat (MBSC is a healthcare product in Asian countries. The aim of this study was to investigate the effect of an MBSC ethanol extract on the bioavailability of cyclosporine A (CsA in rats. Rats were orally dosed with CsA alone or in combination with MBSC ethanol extracts (500 mg/kg, p.o.. The blood levels of CsA were assayed by liquid chromatography with an electrospray ionization source and tandem mass spectrometry (LC-MS/MS. The everted rat intestinal sac technique was used to determine the influence of MBSC on the absorption of CsA. The results reveal that combined CsA intake with MBSC decreased the Cmax, AUC0-t, t1/2z and MRT0-t values of CsA by 24.96%, 47.28%, 34.73% and 23.58%, respectively (P<0.05, and significantly raised the CL/F by 51.97% (P<0.01. The in vitro results demonstrated that significantly less CsA was absorbed (P<0.05. The overall results indicate that after being concomitantly ingested, MBSC reduced the bioavailability of CsA, at least partially, in the absorption phase.

  19. A1 noradrenergic neurons lesions reduce natriuresis and hypertensive responses to hypernatremia in rats.

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    Elaine Fernanda da Silva

    Full Text Available Noradrenergic neurons in the caudal ventrolateral medulla (CVLM; A1 group contribute to cardiovascular regulation. The present study assessed whether specific lesions in the A1 group altered the cardiovascular responses that were evoked by hypertonic saline (HS infusion in non-anesthetized rats. Male Wistar rats (280-340 g received nanoinjections of antidopamine-β-hydroxylase-saporin (A1 lesion, 0.105 ng.nL(-1 or free saporin (sham, 0.021 ng.nL(-1 into their CVLMs. Two weeks later, the rats were anesthetized (2% halothane in O2 and their femoral artery and vein were catheterized and led to exit subcutaneously between the scapulae. On the following day, the animals were submitted to HS infusion (3 M NaCl, 1.8 ml • kg(-1, b.wt., for longer than 1 min. In the sham-group (n = 8, HS induced a sustained pressor response (ΔMAP: 35±3.6 and 11±1.8 mmHg, for 10 and 90 min after HS infusion, respectively; P<0.05 vs. baseline. Ten min after HS infusion, the pressor responses of the anti-DβH-saporin-treated rats (n = 11were significantly smaller(ΔMAP: 18±1.4 mmHg; P<0.05 vs. baseline and vs. sham group, and at 90 min, their blood pressures reached baseline values (2±1.6 mmHg. Compared to the sham group, the natriuresis that was induced by HS was reduced in the lesioned group 60 min after the challenge (196±5.5 mM vs. 262±7.6 mM, respectively; P<0.05. In addition, A1-lesioned rats excreted only 47% of their sodium 90 min after HS infusion, while sham animals excreted 80% of their sodium. Immunohistochemical analysis confirmed a substantial destruction of the A1 cell group in the CVLM of rats that had been nanoinjected withanti-DβH-saporin. These results suggest that medullary noradrenergic A1 neurons are involved in the excitatory neural pathway that regulates hypertensive and natriuretic responses to acute changes in the composition of body fluid.

  20. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

    Science.gov (United States)

    Tawa, N E; Odessey, R; Goldberg, A L

    1997-07-01

    Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting.

  1. Reduced astrocyte density underlying brain volume reduction in activity-based anorexia rats

    Science.gov (United States)

    Frintrop, Linda; Liesbrock, Johanna; Paulukat, Lisa; Johann, Sonja; Kas, Martien J; Tolba, Rene; Heussen, Nicole; Neulen, Joseph; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

    2018-04-01

    Severe grey and white matter volume reductions were found in patients with anorexia nervosa (AN) that were linked to neuropsychological deficits while their underlying pathophysiology remains unclear. For the first time, we analysed the cellular basis of brain volume changes in an animal model (activity-based anorexia, ABA). Female rats had 24 h/day running wheel access and received reduced food intake until a 25% weight reduction was reached and maintained for 2 weeks. In ABA rats, the volumes of the cerebral cortex and corpus callosum were significantly reduced compared to controls by 6% and 9%, respectively. The number of GFAP-positive astrocytes in these regions decreased by 39% and 23%, total astrocyte-covered area by 83% and 63%. In neurons no changes were observed. The findings were complemented by a 60% and 49% reduction in astrocyte (GFAP) mRNA expression. Volumetric brain changes in ABA animals mirror those in human AN patients. These alterations are associated with a reduction of GFAP-positive astrocytes as well as GFAP expression. Reduced astrocyte functioning could help explain neuronal dysfunctions leading to symptoms of rigidity and impaired learning. Astrocyte loss could constitute a new research target for understanding and treating semi-starvation and AN.

  2. Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat

    Science.gov (United States)

    Wang, T. M.; Hsu, J. F.; Jee, W. S.; Matthews, J. L.

    1993-01-01

    The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

  3. Blood pressure reducing effects of Phalaris canariensis in normotensive and spontaneously hypertensive rats.

    Science.gov (United States)

    Passos, Clévia Santos; Carvalho, Lucimeire Nova; Pontes, Roberto Braz; Campos, Ruy Ribeiro; Ikuta, Olinda; Boim, Mirian Aparecida

    2012-02-01

    The birdseed Phalaris canariensis (Pc) is popularly used as an antihypertensive agent. The aqueous extract of Pc (AEPc) was administered in adult normotensive Wistar rats and spontaneously hypertensive rats (SHR) and in prehypertensive young SHR (SHR(Y), 3 weeks old). Animals received AEPc (400 mg·kg(-1)·day(-1), by gavage) for 30 days, then groups were divided into 2 subgroups: one was treated for another 30 days and the other received water instead of AEPc for 30 days. AEPc reduced systolic blood pressure (SBP) in both adult groups; however, treatment interruption was followed by a gradual return of the SBP to baseline levels. SHR(Y) became hypertensive 30 days after weaning. AEPc minimized the increase in SBP in SHR(Y), but blood pressure rose to levels similar to those in the untreated group with treatment interruption. There were no changes in renal function, diuresis, or Na(+) excretion. Pc is rich in tryptophan, and the inhibition of the metabolism of tryptophan to kynurenine, a potential vasodilator factor, prevented the blood pressure reducing effect of AEPc. Moreover, AEPc significantly reduced sympathoexcitation. Data indicate that the metabolic derivative of tryptophan, kynurenine, may be a mediator of the volume-independent antihypertensive effect of Pc, which was at least in part mediated by suppression of the sympathetic tonus.

  4. Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Marcelo Mendonça Mota

    2014-07-01

    Full Text Available Background: Resistance exercise effects on cardiovascular parameters are not consistent. Objectives: The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Methods: Wistar rats were divided into three groups: control group (n = 8; sedentary diabetic (n = 8; and trained diabetic (n = 8. Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. Results: A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2% and an increase in the trained diabetic group (95 ± 3% without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05 in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05 in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg as compared to the sedentary diabetic group. Conclusions: Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.

  5. Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats

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    Roberto Furlanetto Jr

    2017-02-01

    Full Text Available Objective: We studied the effect of resistance exercise (RE on mRNA levels of atrogin-1, MuRF-1, and myostatin in the gastrocnemius muscle of arthritic rats after loss of ovarian function (LOF. Material and methods : Thirty female Wistar rats (nine weeks old, 195.3 ±17.4 grams were randomly allocated into five groups: control group (CT-Sham; n = 6; group with rheumatoid arthritis (RA; n = 6; group with rheumatoid arthritis subjected to RE (RAEX; n = 6; ovariectomy group with rheumatoid arthritis (RAOV; n = 6; and an ovariectomy group with rheumatoid arthritis subjected to RE (RAOVEX; n = 6. After 15 days of intra-articular injections with Met-BSA the animals were subjected to RE and six hours after workout were euthanised. Results : The rheumatoid arthritis provoked reduction in the cross-sectional area (CSA of muscle fibres, but the CSA was lower in the RAOV when compared to the RA groups. Skeletal muscle atrogin-1 mRNA level was increased in arthritic rats (RA and RAOV, but the atrogin-1 level was higher in RAOV group when compared to other arthritic groups. The Muscle MuRF-1 mRNA level was also increased in the RAOV group. The increased atrogin-1 and MuRF-1 mRNA levels were lower in the RAOVEX group than in the RAOV group. The myostatin mRNA level was similar in all groups, except for the RAOVEX group, in which it was lower than the other groups. Conclusions : LOF results in increased loss of skeletal muscle-related ubiquitin ligases (atrogin-1 and MuRF-1. However, the RE reduces the atrogin-1, MuRF-1, and myostatin mRNA levels in muscle of arthritic rats affected by LOF.

  6. Brown Norway chromosome 1 congenic reduces symptoms of renal disease in fatty Zucker rats.

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    Craig H Warden

    Full Text Available We previously reported that a congenic rat with Brown Norway (BN alleles on chromosome 1 reduces renal disease of 15-week old fatty Zucker rats (ZUC. Development of renal disease in fatty BN congenic and fatty ZUC rats from 9 through 28 weeks is now examined. Analysis of urine metabolites by (1H nuclear magnetic resonance (NMR spectroscopy revealed a significantly increased urinary loss of glucose, myo-inositol, urea, creatine, and valine in ZUC. Food intake was lower in the BN congenic rats at weeks 9-24, but they weighed significantly more at 28 weeks compared with the ZUC group. Fasting glucose was significantly higher in ZUC than congenic and adiponectin levels were significantly lower in ZUC, but there was no significant genotype effect on Insulin levels. Glucose tolerance tests exhibited no significant differences between ZUC and congenic when values were normalized to basal glucose levels. Quantitative PCR on livers revealed evidence for higher gluconeogenesis in congenics than ZUC at 9 weeks. Plasma urea nitrogen and creatinine were more than 2-fold higher in 28-week ZUC. Twelve urine protein markers of glomerular, proximal and distal tubule disease were assayed at three ages. Several proteins that indicate glomerular and proximal tubular disease increased with age in both congenic and ZUC. Epidermal growth factor (EGF level, a marker whose levels decrease with distal tubule disease, was significantly higher in congenics. Quantitative histology of 28 week old animals revealed the most significant genotype effect was for tubular dilation and intratubular protein. The congenic donor region is protective of kidney disease, and effects on Type 2 diabetes are likely limited to fasting glucose and adiponectin. The loss of urea together with a small increase of food intake in ZUC support the hypothesis that nitrogen balance is altered in ZUC from an early age.

  7. Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

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    Mota, Marcelo Mendonça; Silva, Tharciano Luiz Teixeira Braga da; Fontes, Milene Tavares; Barreto, André Sales; Araújo, João Eliakim dos Santos [Departamento de Fisiologia - Universidade Federal de Sergipe (UFS), São Cristóvão, SE (Brazil); Oliveira, Antônio Cesar Cabral de; Wichi, Rogério Brandão [Departamento de Educação Física - UFS, São Cristóvão, SE (Brazil); Santos, Márcio Roberto Viana, E-mail: marciorvsantos@bol.com.br [Departamento de Fisiologia - Universidade Federal de Sergipe (UFS), São Cristóvão, SE (Brazil)

    2014-07-15

    Resistance exercise effects on cardiovascular parameters are not consistent. The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group. Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.

  8. Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

    International Nuclear Information System (INIS)

    Mota, Marcelo Mendonça; Silva, Tharciano Luiz Teixeira Braga da; Fontes, Milene Tavares; Barreto, André Sales; Araújo, João Eliakim dos Santos; Oliveira, Antônio Cesar Cabral de; Wichi, Rogério Brandão; Santos, Márcio Roberto Viana

    2014-01-01

    Resistance exercise effects on cardiovascular parameters are not consistent. The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group. Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats

  9. Amlodipine reduces the antimigratory effect of diclofenac in spontaneously hypertensive rats.

    Science.gov (United States)

    Rodrigues, Stephen Fernandes; Dossantos, Rosangela Aparecida; de Oliveira, Maria Aparecida; Rastelli, Viviani Milan; Nucci, Gilberto de; Tostes, Rita de Cássia; Nigro, Dorothy; Carvalho, Maria Helena; Fortes, Zuleica B

    2008-05-01

    Amlodipine, an antihypertensive drug, and diclofenac, an antiinflammatory drug, may generally be combined, particularly in elderly patients; therefore, the potential for their interaction is high. We aim to determine if amlodipine interferes with the antimigratory effect of diclofenac. For this, male spontaneously hypertensive rats (SHRs) were treated with either diclofenac (1 mg.kg.d, 15 d) alone or combined with amlodipine (10 mg.kg.d, 15 d). Leukocyte rolling, adherence, and migration were studied by intravital microscopy. Diclofenac did not change (180.0 +/- 2.3), whereas amlodipine combined (163.4 +/- 5.1) or not (156.3 +/- 4.3) with diclofenac reduced the blood pressure (BP) levels in SHR (183.1 +/- 4.4). Diclofenac and amlodipine reduced leukocyte adherence, migration, and ICAM-1 expression, whereas only diclofenac reduced rolling leukocytes as well. Combined with amlodipine, the effect of the diclofenac was reduced. Neither treatment tested increased the venular shear rate or modified the venular diameters, number of circulating leukocytes, P-selectin, PECAM-1, L-selectin, or CD-18 expressions. No difference could be found in plasma concentrations of both drugs given alone or in association. In conclusion, amlodipine reduces leukocyte migration in SHR, reducing endothelial cell ICAM-1 expression. Amlodipine reduces the effect of the diclofenac, possibly by the same mechanism. A pharmacokinetic interaction as well as an effect on the other adhesion molecules tested could be discarded.

  10. Remote ischemic preconditioning fails to reduce infarct size in the Zucker fatty rat model of type-2 diabetes: role of defective humoral communication.

    Science.gov (United States)

    Wider, Joseph; Undyala, Vishnu V R; Whittaker, Peter; Woods, James; Chen, Xuequn; Przyklenk, Karin

    2018-03-09

    Remote ischemic preconditioning (RIPC), the phenomenon whereby brief ischemic episodes in distant tissues or organs render the heart resistant to infarction, has been exhaustively demonstrated in preclinical models. Moreover, emerging evidence suggests that exosomes play a requisite role in conveying the cardioprotective signal from remote tissue to the myocardium. However, in cohorts displaying clinically common comorbidities-in particular, type-2 diabetes-the infarct-sparing effect of RIPC may be confounded for as-yet unknown reasons. To investigate this issue, we used an integrated in vivo and in vitro approach to establish whether: (1) the efficacy of RIPC is maintained in the Zucker fatty rat model of type-2 diabetes, (2) the humoral transfer of cardioprotective triggers initiated by RIPC are transported via exosomes, and (3) diabetes is associated with alterations in exosome-mediated communication. We report that a standard RIPC stimulus (four 5-min episodes of hindlimb ischemia) reduced infarct size in normoglycemic Zucker lean rats, but failed to confer protection in diabetic Zucker fatty animals. Moreover, we provide novel evidence, via transfer of serum and serum fractions obtained following RIPC and applied to HL-1 cardiomyocytes subjected to hypoxia-reoxygenation, that diabetes was accompanied by impaired humoral communication of cardioprotective signals. Specifically, our data revealed that serum and exosome-rich serum fractions collected from normoglycemic rats attenuated hypoxia-reoxygenation-induced HL-1 cell death, while, in contrast, exosome-rich samples from Zucker fatty rats did not evoke protection in the HL-1 cell model. Finally, and unexpectedly, we found that exosome-depleted serum from Zucker fatty rats was cytotoxic and exacerbated hypoxia-reoxygenation-induced cardiomyocyte death.

  11. Fenofibrate Administration Reduces Alcohol and Saccharin Intake in Rats: Possible Effects at Peripheral and Central Levels

    Directory of Open Access Journals (Sweden)

    Mario Rivera-Meza

    2017-07-01

    Full Text Available We have previously shown that the administration of fenofibrate to high-drinker UChB rats markedly reduces voluntary ethanol intake. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα agonist, which induces the proliferation of peroxisomes in the liver, leading to increases in catalase levels that result in acetaldehyde accumulation at aversive levels in the blood when animals consume ethanol. In these new studies, we aimed to investigate if the effect of fenofibrate on ethanol intake is produced exclusively in the liver (increasing catalase and systemic levels of acetaldehyde or there might be additional effects at central level. High drinker rats (UChB were allowed to voluntary drink 10% ethanol for 2 months. Afterward, a daily dose of fenofibrate (25, 50 or 100 mg/kg/day or vehicle (as control was administered orally for 14 days. Voluntary ethanol intake was recorded daily. After that time, animals were deprived of ethanol access for 24 h and administered with an oral dose of ethanol (1 g/kg for acetaldehyde determination in blood. Fenofibrate reduced ethanol voluntary intake by 60%, in chronically drinking rats, at the three doses tested. Acetaldehyde in the blood rose up to between 80 μM and 100 μM. Considering the reduction of ethanol consumption, blood acetaldehyde levels and body weight evolution, the better results were obtained at a dose of 50 mg fenofibrate/kg/day. This dose of fenofibrate also reduced the voluntary intake of 0.2% saccharin by 35% and increased catalase levels 2.5-fold in the liver but showed no effects on catalase levels in the brain. To further study if fenofibrate administration changes the motivational properties of ethanol, a conditioned-place preference experiment was carried out. Animals treated with fenofibrate (50 mg/kg/day did not develop ethanol-conditioned place preference (CPP.In an additional experiment, chronically ethanol-drinking rats underwent two cycles of ethanol

  12. Molecular hydrogen ameliorates several characteristics of preeclampsia in the Reduced Uterine Perfusion Pressure (RUPP) rat model.

    Science.gov (United States)

    Ushida, Takafumi; Kotani, Tomomi; Tsuda, Hiroyuki; Imai, Kenji; Nakano, Tomoko; Hirako, Shima; Ito, Yumiko; Li, Hua; Mano, Yukio; Wang, Jingwen; Miki, Rika; Yamamoto, Eiko; Iwase, Akira; Bando, Yasuko K; Hirayama, Masaaki; Ohno, Kinji; Toyokuni, Shinya; Kikkawa, Fumitaka

    2016-12-01

    Oxidative stress plays an important role in the pathogenesis of preeclampsia. Recently, molecular hydrogen (H 2 ) has been shown to have therapeutic potential in various oxidative stress-related diseases. The aim of this study is to investigate the effect of H 2 on preeclampsia. We used the reduced utero-placental perfusion pressure (RUPP) rat model, which has been widely used as a model of preeclampsia. H 2 water (HW) was administered orally ad libitum in RUPP rats from gestational day (GD) 12-19, starting 2 days before RUPP procedure. On GD19, mean arterial pressure (MAP) was measured, and samples were collected. Maternal administration of HW significantly decreased MAP, and increased fetal and placental weight in RUPP rats. The increased levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and diacron reactive oxygen metabolites as a biomarker of reactive oxygen species in maternal blood were decreased by HW administration. However, vascular endothelial growth factor level in maternal blood was increased by HW administration. Proteinuria, and histological findings in kidney were improved by HW administration. In addition, the effects of H 2 on placental villi were examined by using a trophoblast cell line (BeWo) and villous explants from the placental tissue of women with or without preeclampsia. H 2 significantly attenuated hydrogen peroxide-induced sFlt-1 expression, but could not reduce the expression induced by hypoxia in BeWo cells. H 2 significantly attenuated sFlt-1 expression in villous explants from women with preeclampsia, but not affected them from normotensive pregnancy. The prophylactic administration of H 2 attenuated placental ischemia-induced hypertension, angiogenic imbalance, and oxidative stress. These results support the theory that H 2 has a potential benefit in the prevention of preeclampsia. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Fenugreek with reduced bitterness prevents diet-induced metabolic disorders in rats

    Directory of Open Access Journals (Sweden)

    Muraki Etsuko

    2012-05-01

    Full Text Available Abstract Background Various therapeutic effects of fenugreek (Trigonella foenum-graecum L. on metabolic disorders have been reported. However, the bitterness of fenugreek makes it hard for humans to eat sufficient doses of it for achieving therapeutic effects. Fenugreek contains bitter saponins such as protodioscin. Fenugreek with reduced bitterness (FRB is prepared by treating fenugreek with beta-glucosidase. This study has been undertaken to evaluate the effects of FRB on metabolic disorders in rats. Methods Forty Sprague–Dawley rats were fed with high-fat high-sucrose (HFS diet for 12 week to induce mild glucose and lipid disorders. Afterwards, the rats were divided into 5 groups. In the experiment 1, each group (n = 8 was fed with HFS, or HFS containing 2.4% fenugreek, or HFS containing 1.2%, 2.4% and 4.8% FRB, respectively, for 12 week. In the experiment 2, we examined the effects of lower doses of FRB (0.12%, 0.24% and 1.2% under the same protocol (n = 7 in each groups. Results In the experiment 1, FRB dose-dependently reduced food intake, body weight gain, epididymal white adipose tissue (EWAT and soleus muscle weight. FRB also lowered plasma and hepatic lipid levels and increased fecal lipid levels, both dose-dependently. The Plasma total cholesterol levels (mmol/L in the three FRB and Ctrl groups were 1.58 ± 0.09, 1.45 ± 0.05*, 1.29 ± 0.07* and 2.00 ± 0.18, respectively (*; P P P  Conclusions Thus we have demonstrated that FRB (1.2 ~ 4.8% prevents diet-induced metabolic disorders such as insulin resistance, dyslipidemia and fatty liver.

  14. Hepatoprotective Flavonoids in Opuntia ficus-indica Fruits by Reducing Oxidative Stress in Primary Rat Hepatocytes.

    Science.gov (United States)

    Kim, Jung Wha; Kim, Tae Bum; Kim, Hyun Woo; Park, Sang Wook; Kim, Hong Pyo; Sung, Sang Hyun

    2017-01-01

    Liver disorder was associated with alcohol consumption caused by hepatic cellular damages. Opuntia ficus-indica fruit extracts (OFIEs), which contain betalain pigments and polyphenols including flavonoids, have been introduced as reducing hangover symptoms and liver protective activity. To evaluate hepatoprotective activity of OFIEs and isolated compounds by high-speed countercurrent chromatography (HSCCC). The extract of O. ficus-indica fruits was fractionated into methylene chloride and n -butanol. The n -butanol fraction was isolated by HSCCC separation (methylene chloride-methanol- n -butanol-water, 5:4:3:5, v/v/v/v). The hepatoprotective activity of OFIEs and isolated compounds was evaluated on rat primary hepatocytes against ethanol-induced toxicity. Antioxidative parameters such as glutathione reductase and glutathione peroxidase (GSH-P x ) enzymes and the GSH content were measured. Two flavonoids, quercetin 3- O -methyl ester (1) and (+)-taxifolin, and two flavonoid glycosides, isorhamnetin 3- O -β- d -glucoside (3) and narcissin (4), were isolated from the n -butanol fraction by HSCCC separation. Among them, compound 2 significantly protected rat primary hepatocytes against ethanol exposure by preserving antioxidative properties of GR and GSH-P x . OFIEs and (+)-taxifolin were suggested to reduce hepatic damage by alcoholic oxidative stress. Hepatoprotective Flavonoids were isolated from Opuntia ficus-indica by high -speed countercurrent chromatography (HSCCC).

  15. Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney.

    Science.gov (United States)

    Engbersen, R; Moons, M M; Wouterse, A C; Dijkman, H B; Kramers, C; Smits, P; Russel, F G

    2000-08-01

    Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 microM) and glibenclamide (10 microM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3+/-1.5 for hypoxic perfusions vs 4.9+/-1.6 for normoxic perfusions, mean +/- s.e. mean, P<0.05), which could be completely restored by 200 microM tolbutamide (5.7+/-0.4 for tolbutamide vs 14.3+/-1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220+/-100 mU for tolbutamide vs. 1220+/-160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 microM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations.

  16. Photobiomodulation Leads to Reduced Oxidative Stress in Rats Submitted to High-Intensity Resistive Exercise

    Directory of Open Access Journals (Sweden)

    Helenita Antonia de Oliveira

    2018-01-01

    Full Text Available The aim of this study was to determine whether oxidative stress markers are influenced by low-intensity laser therapy (LLLT in rats subjected to a high-intensity resistive exercise session (RE. Female Wistar rats divided into three experimental groups (Ctr: control, 4J: LLLT, and RE and subdivided based on the sampling times (instantly or 24 h postexercise underwent irradiation with LLLT using three-point transcutaneous method on the hind legs, which was applied to the gastrocnemius muscle at the distal, medial, and proximal points. Laser (4J or placebo (device off were carried out 60 sec prior to RE that consisted of four climbs bearing the maximum load with a 2 min time interval between each climb. Lipoperoxidation levels and antioxidant capacity were obtained in muscle. Lipoperoxidation levels were increased (4-HNE and CL markers instantly post-RE. LLLT prior to RE avoided the increase of the lipid peroxidation levels. Similar results were also notified for oxidation protein assays. The GPx and FRAP activities did not reduce instantly or 24 h after RE. SOD increased 24 h after RE, while CAT activity did not change with RE or LLLT. In conclusion, LLLT prior to RE reduced the oxidative stress markers, as well as, avoided reduction, and still increased the antioxidant capacity.

  17. Reduced glomerular angiotensin II receptor density in diabetes mellitus in the rat: time course and mechanism

    International Nuclear Information System (INIS)

    Wilkes, B.M.

    1987-01-01

    Glomerular angiotensin II receptors are reduced in number in early diabetes mellitus, which may contribute to hyperfiltration and glomerular injury. The time course and role of the renin-angiotensin-aldosterone system in the pathogenesis of the receptor abnormality were studied in male Sprague-Dawley rats made diabetic with streptozotocin (65 mg, iv). Glomerular angiotensin II receptors were measured by Scatchard analysis; insulin, renin activity, angiotensin II, and aldosterone were measured by RIA. Diabetes mellitus was documented at 24 h by a rise in plasma glucose (vehicle-injected control, 133 +/- 4; diabetic, 482 +/- 22 mg/dl and a fall in plasma insulin (control, 53.1 +/- 5.7; diabetic, 35.6 +/- 4.0 microIU/ml. At 24 h glomerular angiotensin II receptor density was decreased by 26.5% in diabetic rats (control, 75.5 +/- 9.6 X 10(6); diabetic, 55.5 +/- 8.3 X 10(6) receptors/glomerulus. Receptor occupancy could not explain the defect, because there was reduced binding in diabetic glomeruli after pretreatment with 3 M MgCl 2 , a maneuver that caused dissociation of previously bound hormone. There was a progressive return of the receptor density toward normal over the 60 days following induction of diabetes, with diabetic glomeruli measuring 22.7%, 14.8%, and 3.7% fewer receptors than age-matched controls at 11 days, 1 month, and 2 months, respectively

  18. The influence of age on the effectiveness of DTPA in reducing 141Ce retention in rats

    International Nuclear Information System (INIS)

    Kargacin, B.; Kostial, K.; Landeka, M.

    1983-01-01

    The influence of age on the effectiveness of chelation treatment in reducing retention of radioactive cerium was studied in two- and six-week-old albino rats. 141 Ce was administered intraperitoneally, followed immediately and after 24 and 48 hours by intraperitoneal administration of the tri-sodium calcium salt of diethylenetriaminepentaacetic acid-Na 3 (CaDTPA) at 380 μmol/kg body weight. The whole-body retention was determined 2, 4 and 6 days after radiocerium administration, when the animals were killed and the organ retention was determined. The chelation therapy significantly reduced the whole-body retention of radiocerium. This treatment was however twice as effective in older as in younger animals. (author)

  19. Diphenhydramine and hyaluronic acid derivatives reduce adnexal adhesions and prevent tubal obstructions in rats.

    Science.gov (United States)

    Avsar, Ayse Filiz; Avsar, Fatih Mehmet; Sahin, Mustafa; Topaloglu, Serdar; Vatansev, Husamettin; Belviranli, Metin

    2003-01-10

    The purpose of this study is to investigate the effects of diphenhydramine-HCl and Na-hyaluronate derivatives on the development of postoperative peritoneal adhesion and tubal obstruction. Forty female rats of Sprague-Dawley type were used in the study. The rats were divided into four groups, each comprising 10 subjects. After all the rats were anaesthetized with 50mg/kg ketamine HCl, their abdomens were opened with a lower midline incision. Injury was induced on the right pelvic peritoneum and on the peritoneal surface of left uterine tube. No additional procedure was applied to the first group. 10 mg/kg diphenhydramine-HCl was given to the second group intravenously. In the third group, 0.25 mg/kg Orthovisc, a Na-hyaluronate derivative was diluted with 2 ml physiological saline and poured into the abdomen. For the fourth group, Seprafilm, a Na-hyaluronate derivative was covered in a layer of 0.7 cm x 3 cm over the left uterine tube. After 14 days, the rats were anaesthetized with ketamine HCl again, and 5 cm(3) blood sample was taken with cardiac puncture. The abdomen was opened with an incision transverse to the upper end of the midline incision, and the presence of adhesions was investigated. Detected adhesions were staged according to the Mazuji classification. Tubal patencies were inspected by injecting methylene blue from the uterine corpus into the lumen using an injector. A piece of abdominal wall of 4 cm x 4 cm was removed by extending the incision in the reverse U shape. The tensile strength and bursting pressure of the suture line were determined using the Peacock method. One gram of tissue was taken from the incision line, and hydroxyproline levels were determined by the Bergman-Loxley method. Aspartate aminotransferase (AST) levels were measured. All of the rats completed the study. AST levels, tissue hydroxyproline levels and tensile strength and bursting pressure test results were found to be similar in all groups. While adhesion rates in the groups

  20. Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

    Science.gov (United States)

    Briggs, Scott A; Hall, Brandon J; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H; Rose, Jed E; Levin, Edward D

    2016-03-01

    Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (pdextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self-administration replicating previous findings. Augmenting interactions were observed with

  1. Progranulin Reduced Neuronal Cell Death by Activation of Sortilin 1 Signaling Pathways After Subarachnoid Hemorrhage in Rats.

    Science.gov (United States)

    Li, Bo; He, Yue; Xu, Liang; Hu, Qin; Tang, Junjia; Chen, Yujie; Tang, Jiping; Feng, Hua; Zhang, John H

    2015-08-01

    Progranulin has been reported to have neuroprotective actions in cultured neurons. This study investigated the effect of recombinant rat progranulin on early brain injury after subarachnoid hemorrhage. Controlled in vivo laboratory study. Animal research laboratory. Two hundred thirty adult male Sprague-Dawley rats weighing 280-320 g. Subarachnoid hemorrhage was induced in rats by endovascular perforation. Rat recombinant progranulin (1 and 3 ng) was administrated intracerebroventricularly at 1.5 hours after subarachnoid hemorrhage. Progranulin small interfering RNA was administrated by intracerebroventricularly at 1 day before subarachnoid hemorrhage induction. Subarachnoid hemorrhage grade, neurologic score, and brain water content were measured at 24 and 72 hours after subarachnoid hemorrhage. Neural apoptosis was evaluated by double immunofluorescence staining using terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick-end labeling and neuronal nuclei. For mechanistic study, the expression of progranulin, phosphorylated Akt, Akt, p-Erk, Erk, Bcl-2, and cleaved caspase-3 were analyzed by Western blot at 24 hours after subarachnoid hemorrhage. siRNA for sortilin 1 (a progranulin receptor) was used to intervene the downstream pathway. The expression of progranulin decreased and reached the lowest point at 24 hours after subarachnoid hemorrhage. Administration of rat recombinant progranulin decreased brain water content and improved neurologic functions at both 24 and 72 hours after subarachnoid hemorrhage, while knockdown of endogenous progranulin aggravated neurologic deficits after subarachnoid hemorrhage. Rat recombinant progranulin treatment reduced neuronal apoptosis, while progranulin deficiency promoted neuronal apoptosis at 24 hours after subarachnoid hemorrhage. Rat recombinant progranulin promoted Akt activation, increased Bcl-2 level, but reduced caspase-3 level. Knockdown of progranulin binding factor sortilin 1

  2. Pyrrolidin-2-one derivatives may reduce body weight in rats with diet-induced obesity.

    Science.gov (United States)

    Dudek, Magdalena; Knutelska, Joanna; Bednarski, Marek; Nowiński, Leszek; Zygmunt, Małgorzata; Kazek, Grzegorz; Mordyl, Barbara; Głuch-Lutwin, Monika; Zaręba, Paula; Kulig, Katarzyna; Sapa, Jacek

    2016-04-05

    Obesity affects an increasing number of individuals in the human population and significant importance is attached to research leading to the discovery of drug which would effectively reduce weight. The search for new drugs with anorectic activity and acting within the adrenergic system has attracted the interest of researchers. This study concerns the experimental effects on body weight of α2-adrenoceptor antagonists from the group of pyrrolidin-2-one derivatives in rats with diet-induced obesity. The intrinsic activity of the test compounds at the α-adrenoreceptors was tested. Obesity in rats was obtained by the use of fatty diet and then the influence of the test compounds on body weight, food and water intakes, lipid and glucose profiles and glycerol and cortisol levels were determinated. The effects of the compounds on locomotor activity, body temperature, blood pressure and heart rate were tested. One of the test compounds (1-(3-(4-phenylpiperazin-1-yl)propyl)pyrrolidin-2-one) reduces the animal's body weight and the amount of peritoneal adipose tissue during chronic administration, at the same time it does not cause significant adverse effects on the cardiovascular system. This compound decreases temperature and elevates glycerol levels and does not change the locomotor activity and cortisol level at anti-obese dose. Some derivatives of pyrrolidin-2-one that act as antagonists of the α2-adrenoreceptor may reduce body weight. Reducing body weight for 1-(3-(4-phenylpiperazin-1-yl)propyl)pyrrolidin-2-one can be associated with decrease in food intake, body fat reduction, reduction of blood glucose, and increased thermogenesis and lipolysis. This effect cannot be the result of changes in spontaneous activity or stress. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Melatonin reduces motivation for cocaine self-administration and prevents relapse-like behavior in rats.

    Science.gov (United States)

    Takahashi, Tatiane T; Vengeliene, Valentina; Spanagel, Rainer

    2017-06-01

    Melatonin is a hormone involved in the entrainment of circadian rhythms, which appears dysregulated in drug users. Further, it has been demonstrated that melatonin can modulate the reinforcing effects of several drugs of abuse and may therefore play a role in drug addiction. Here, we investigated whether administration of melatonin reduces relapse-like behavior and the motivation to seek cocaine in rats. Male Sprague-Dawley rats were submitted to long-term cocaine self-administration training. Thereafter, melatonin effects were assessed on: (1) the motivation to work for cocaine in the break point test, (2) the relapse-like behavior in the cue-induced reinstatement test, (3) the distance traveled in the open field test, and (4) sucrose preference in a two-bottle choice paradigm. Melatonin, 25 or 50 mg/kg, was injected 3-4 h after the dark phase onset, 30 min prior to each test. Both doses of melatonin decreased the number of active pokes in both break point and cue-induced reinstatement tests, demonstrating that melatonin can reduce the cocaine-seeking behavior and the motivation to work for cocaine. Administration of the higher dose of this hormone, however, significantly reduced the number of inactive pokes during the cue-induced reinstatement test and tended to reduce animals' locomotor activity in the open field test. Sucrose preference was unchanged in both vehicle- and melatonin-treated animal groups. Our data suggest that melatonin administration may lower the risk of relapse triggered by cues in cocaine-experienced animals.

  4. Biobreeding rat islets exhibit reduced antioxidative defense and N-acetyl cysteine treatment delays type 1 diabetes

    Science.gov (United States)

    Bogdani, Marika; Henschel, Angela M.; Kansra, Sanjay; Fuller, Jessica M.; Geoffrey, Rhonda; Jia, Shuang; Kaldunski, Mary L.; Pavletich, Scott; Prosser, Simon; Chen, Yi-Guang; Lernmark, Åke; Hessner, Martin J.

    2014-01-01

    Islet-level oxidative stress has been proposed as a trigger for type 1 diabetes (T1D), and release of cytokines by infiltrating immune cells further elevates reactive oxygen species (ROS), exacerbating β cell duress. To identify genes/mechanisms involved with diabeto-genesis at the β cell level, gene expression profiling and targeted follow-up studies were used to investigate islet activity in the biobreeding (BB) rat. Forty-day-old spontaneously diabetic lymphopenic BB DRlyp/lyp rats (before T cell insulitis) as well as nondiabetic BB DR+/+ rats, nondiabetic but lymphopenic F344lyp/lyp rats, and healthy Fischer (F344) rats were examined. Gene expression profiles of BB rat islets were highly distinct from F344 islets and under-expressed numerous genes involved in ROS metabolism, including glutathione S-transferase (GST) family members (Gstm2, Gstm4, Gstm7, Gstt1, Gstp1, and Gstk1), superoxide dismutases (Sod2 and Sod3), peroxidases, and peroxiredoxins. This pattern of under-expression was not observed in brain, liver, or muscle. Compared with F344 rats, BB rat pancreata exhibited lower GST protein levels, while plasma GST activity was found significantly lower in BB rats. Systemic administration of the antioxidant N-acetyl cysteine to DRlyp/lyp rats altered abundances of peripheral eosinophils, reduced severity of insulitis, and significantly delayed but did not prevent diabetes onset. We find evidence of β cell dysfunction in BB rats independent of T1D progression, which includes lower expression of genes related to antioxidative defense mechanisms during the pre-onset period that may contribute to overall T1D susceptibility. PMID:23111281

  5. Surface-Displayed IL-10 by Recombinant Lactobacillus plantarum Reduces Th1 Responses of RAW264.7 Cells Stimulated with Poly(I:C) or LPS.

    Science.gov (United States)

    Cai, Ruopeng; Jiang, Yanlong; Yang, Wei; Yang, Wentao; Shi, Shaohua; Shi, Chunwei; Hu, Jingtao; Gu, Wei; Ye, Liping; Zhou, Fangyu; Gong, Qinglong; Han, Wenyu; Yang, Guilian; Wang, Chunfeng

    2016-02-01

    Recently, poly-γ-glutamic acid synthetase A (pgsA) has been applied to display exogenous proteins on the surface of Lactobacillus casei or Lactococcus lactis, which results in a surfacedisplayed component of bacteria. However, the ability of carrying genes encoded by plasmids and the expression efficiency of recombinant bacteria can be somewhat affected by the longer gene length of pgsA (1,143 bp); therefore, a truncated gene, pgsA, was generated based on the characteristics of pgsA by computational analysis. Using murine IL-10 as an exogenous gene, recombinant Lactobacillus plantarum was constructed and the capacity of the surface-displayed protein and functional differences between exogenous proteins expressed by these strains were evaluated. Surface expression of IL-10 on both recombinant bacteria with anchorins and the higher expression levels in L. plantarum-pgsA'-IL-10 were confirmed by western blot assay. Most importantly, up-regulation of IL-1β, IL-6, TNF-α, IFN-γ, and the nuclear transcription factor NF-κB p65 in RAW264.7 cells after stimulation with Poly(I:C) or LPS was exacerbated after co-culture with L. plantarum-pgsA. By contrast, IL-10 expressed by these recombinant strains could reduce these factors, and the expression of these factors was associated with recombinant strains that expressed anchorin (especially in L. plantarum-pgsA'-IL-10) and was significantly lower compared with the anchorin-free strains. These findings indicated that exogenous proteins could be successfully displayed on the surface of L. plantarum by pgsA or pgsA', and the expression of recombinant bacteria with pgsA' was superior compared with bacteria with pgsA.

  6. Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats

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    Chihiro Moriya

    2016-01-01

    Full Text Available We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD or a 60% high-fat diet (HFD with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects.

  7. Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression.

    Science.gov (United States)

    Siebelt, M; Waarsing, J H; Groen, H C; Müller, C; Koelewijn, S J; de Blois, E; Verhaar, J A N; de Jong, M; Weinans, H

    2014-09-01

    Osteoarthritis (OA) is a non-rheumatoid joint disease characterized by progressive degeneration of extra-cellular cartilage matrix (ECM), enhanced subchondral bone remodeling, osteophyte formation and synovial thickening. Alendronate (ALN) is a potent inhibitor of osteoclastic bone resorption and results in reduced bone remodeling. This study investigated the effects of pre-emptive use of ALN on OA related osteoclastic subchondral bone resorption in an in vivo rat model for severe OA. Using multi-modality imaging we measured effects of ALN treatment within cartilage and synovium. Severe osteoarthritis was induced in left rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with subcutaneous ALN injections and compared to twenty untreated controls. Animals were longitudinally monitored for 12weeks with in vivo μCT to measure subchondral bone changes and SPECT/CT to determine synovial macrophage activation using a folate-based radiotracer. Articular cartilage was analyzed at 6 and 12weeks with ex vivo contrast enhanced μCT and histology to measure sulfated-glycosaminoglycan (sGAG) content and cartilage thickness. ALN treatment successfully inhibited subchondral bone remodeling. As a result we found less subchondral plate porosity and reduced osteophytosis. ALN treatment did not reduce subchondral sclerosis. However, after the OA induction phase, ALN treatment protected cartilage ECM from degradation and reduced synovial macrophage activation. Surprisingly, ALN treatment also improved sGAG content of tibia cartilage in healthy joints. Our data was consistent with the hypothesis that osteoclastic bone resorption might play an important role in OA and may be a driving force for progression of the disease. However, our study suggest that this effect might not solely be effects on osteoclastic activity, since ALN treatment also influenced macrophage functioning. Additionally, ALN treatment and physical activity

  8. A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance

    OpenAIRE

    Bosse, John D.; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E. Dale; Pereira, Troy J.; Dolinsky, Vernon W.; Symons, J. David; Jalili, Thunder

    2013-01-01

    Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-...

  9. Treatment with acarbose, an alpha-glucosidase inhibitor, reduces increased albumin excretion in streptozotocin-diabetic rats.

    Science.gov (United States)

    Cohen, M P; Vasselli, J R; Neuman, R G; Witt, J

    1995-10-01

    1. We examined the effect of the alpha-glucosidase inhibitor acarbose on urinary albumin excretion (UAE) in streptozotocin diabetic rats. 2. Treatment with acarbose for 8 weeks after induction of diabetes prevented the significant increase in UAE observed in untreated diabetic rats relative to nondiabetic controls. 3. Acarbose significantly reduced integrated glycemia, which correlated with albumin excretion rates, and exerts a salutary effect on diabetic renal dysfunction.

  10. Ceftriaxone, a beta-lactam antibiotic, reduces ethanol consumption in alcohol-preferring rats.

    Science.gov (United States)

    Sari, Youssef; Sakai, Makiko; Weedman, Jason M; Rebec, George V; Bell, Richard L

    2011-01-01

    Changes in glutamatergic transmission affect many aspects of neuroplasticity associated with ethanol and drug addiction. For instance, ethanol- and drug-seeking behavior is promoted by increased glutamate transmission in key regions of the motive circuit. We hypothesized that because glutamate transporter 1 (GLT1) is responsible for the removal of most extracellular glutamate, up-regulation or activation of GLT1 would attenuate ethanol consumption. Alcohol-preferring (P) rats were given 24 h/day concurrent access to 15 and 30% ethanol, water and food for 7 weeks. During Week 6, P rats received either 25, 50, 100 or 200 mg/kg ceftriaxone (CEF, i.p.), a β-lactam antibiotic known to elevate GLT1 expression, or a saline vehicle for five consecutive days. Water intake, ethanol consumption and body weight were measured daily for 15 days starting on Day 1 of injections. We also tested the effects of CEF (100 and 200 mg/kg, i.p.) on daily sucrose (10%) consumption as a control for motivated behavioral drinking. Statistical analyses revealed a significant reduction in daily ethanol, but not sucrose, consumption following CEF treatment. During the post treatment period, there was a recovery of ethanol intake across days. Dose-dependent increases in water intake were manifest concurrent with the CEF-induced decreases in ethanol intake. Nevertheless, CEF did not affect body weight. An examination of a subset of the CEF-treated ethanol-drinking rats, on the third day post CEF treatment, revealed increases in GTL1 expression levels within the prefrontal cortex and nucleus accumbens. These results indicate that CEF effectively reduces ethanol intake, possibly through activation of GLT1, and may be a potential therapeutic drug for alcohol addiction treatment.

  11. Phaleria macrocarpa reduces glomerular growth factor expression in alloxan-induced diabetic rats

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    Evy Sulistyoningrum

    2013-08-01

    Full Text Available Background Diabetic nephropathy (DN is the most serious complication of diabetes, causing end-stage renal disease throughout the world. Recent studies have reported a direct role of vascular endothelial growth factor (VEGF and transforming growth factor-â (TGF-â in DN pathogenesis. VEGF and TGF-â are expressed early in glomeruli in response to hyperglycemia. Active substances of Phaleria macrocarpa (PM pericarp are known to have nephroprotective effects. This study aimed to evaluate the effects of Phaleria macrocarpa (Scheff. Boerl pericarp extract on VEGF and TGF-â expression in alloxan-induced diabetic rats. Methods An experimental study was conducted on twenty five male albino (Sprague Dawley rats divided into five groups (of five each: normal control; diabetic; diabetic + metformin 100 mg/kgBW; diabetic + methanolic PM extract 250 mg/kgBW; and diabetic + aqueous PM extract 250 mg/kgBW. Diabetes was induced by alloxan monohydrate 150 mg/BW intraperitoneally. Treatment was given for 3 weeks. VEGF and TGF-â expression analysis was performed by means of immunohistochemical technique. Differences between groups were assessed by one-way ANOVA. Results VEGF expression in the PM extract group was significantly lower than that in the diabetic group and even metformin group (p<0.01. TGF-â expression in methanolic PM extract group was significantly lower than in diabetic and metformin group (p<0.01, but aqueous PM extract group only showed significancy when compared with diabetic group (p< 0.01. Conclusions Phaleria macrocarpa pericarp extract reduces glomerular expression of TGF-â and VEGF in alloxan-induced diabetic rats.

  12. Glycine reduces tissue lipid peroxidation in hypoxia-reoxygenation-induced necrotizing enterocolitis in rats

    Directory of Open Access Journals (Sweden)

    Meyer Karine Furtado

    2006-01-01

    Full Text Available PURPOSE: To assess the protective effect of glycine in an experimental model of Neonatal Necrotizing Enterocolitis (NEC. METHODS: Fifty (50 neonatal Wistar rats, from a litter of six female rats and weighing 4 to 6 grams, were used. Five animals were cannibalized and the 45 remaining were distributed into three groups: the G1 normal control group (n=12; the G2 Group (n=16, of animals that underwent hypoxia-reoxygenation (HR; the G3 Group of animals (n=17 that underwent HR following a 5% intraperitoneal glycine infusion. The animals underwent hypoxia in a CO2 chamber receiving an air flow of 100% CO2 for 5 minutes and reoxygenation receiving an O2 flow at 100% for 5 minutes. One centimeter long small bowel and colon segments were prepared for histological analysis. The rest of the bowel was removed in a block and frozen at minus 80degreesC for homogenization and determination of tissue malondialdehyde (MDA. Tissue lesions were classified as Grade 0 to Grade 5, according to the level of damaged mucosa. RESULTS: The animals in Group G1 had levels of small bowel and colon lesion significantly smaller as compared to the animals in Groups G2 and G3. The G2 group had mean MDA values significantly higher than the animals in the G1 (p = .015 and G3 (p=0.021 groups. MDA values did not differ significantly (p = 0.992 for the animals in groups G1 and G3. CONCLUSION: Glycine reduces tissue MDA levels (a measurement of lipid peroxidation following HR in neonatal rats.

  13. Pyruvate administration reduces recurrent/moderate hypoglycemia-induced cortical neuron death in diabetic rats.

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    Bo Young Choi

    Full Text Available Recurrent/moderate (R/M hypoglycemia is common in type 1 diabetes patients. Moderate hypoglycemia is not life-threatening, but if experienced recurrently it may present several clinical complications. Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored. Pyruvate, however, can be metabolized in the absence of cytosolic NAD. We therefore hypothesized that pyruvate may be able to improve the outcome in diabetic rats subjected to insulin-induced R/M hypoglycemia by terminating hypoglycemia with glucose plus pyruvate, as compared with delivering just glucose alone. In an effort to mimic juvenile type 1 diabetes the experiments were conducted in one-month-old young rats that were rendered diabetic by streptozotocin (STZ, 50mg/kg, i.p. injection. One week after STZ injection, rats were subjected to moderate hypoglycemia by insulin injection (10 U/kg, i.p. without anesthesia for five consecutive days. Pyruvate (500 mg/kg was given by intraperitoneal injection after each R/M hypoglycemia. Three hours after last R/M hypoglycemia, zinc accumulation was evaluated. Three days after R/M hypoglycemia, neuronal death, oxidative stress, microglial activation and GSH concentrations in the cerebral cortex were analyzed. Sparse neuronal death was observed in the cortex. Zinc accumulation, oxidative injury, microglial activation and GSH loss in the cortex after R/M hypoglycemia were all reduced by pyruvate injection. These findings suggest that when delivered alongside glucose, pyruvate may significantly improve the outcome after R/M hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation.

  14. Blockade of central vasopressin receptors reduces the cardiovascular response to acute stress in freely moving rats.

    Science.gov (United States)

    Stojicić, S; Milutinović-Smiljanić, S; Sarenac, O; Milosavljević, S; Paton, J F R; Murphy, D; Japundzić-Zigon, N

    2008-04-01

    To investigate the contribution of central vasopressin receptors to blood pressure (BP) and heart rate (HR) response to stress we injected non-peptide selective V(1a) (SR49059), V(1b) (SSR149415), V(2) (SR121463) receptor antagonists, diazepam or vehicle in the lateral cerebral ventricle of conscious freely moving rats stressed by blowing air on their heads for 2 min. Cardiovascular effects of stress were evaluated by analyzing maximum increase of BP and HR (MAX), latency of maximum response (LAT), integral under BP and HR curve (integral), duration of their recovery and spectral parameters of BP and HR indicative of increased sympathetic outflow (LF(BP) and LF/HF(HR)). Moreover, the increase of serum corticosterone was measured. Exposure to air-jet stress induced simultaneous increase in BP and HR followed by gradual decline during recovery while LF(BP) oscillation remained increased as well as serum corticosterone level. Rats pre-treated with vasopressin receptor antagonists were not sedated while diazepam induced sedation that persisted during exposure to stress. V(1a), V(1b) and V(2) receptor antagonists applied separately did not modify basal values of cardiovascular parameters but prevented the increase in integral(BP). In addition, V(1b) and V(2) receptor antagonists reduced BP(MAX) whereas V(1a), V(1b) antagonist and diazepam reduced HR(MAX) induced by exposure to air-jet stress. All drugs shortened the recovery period, prevented the increase of LF(BP) without affecting the increase in serum corticosterone levels. Results indicate that vasopressin receptors located within the central nervous system mediate, in part, the cardiovascular response to air-jet stress without affecting either the neuroendocrine component or inducing sedation. They support the view that the V(1b) receptor antagonist may be of potential therapeutic value in reducing arterial pressure induced by stress-related disorders.

  15. Linseed Dietary Fibers Reduce Apparent Digestibility of Energy and Fat and Weight Gain in Growing Rats

    Directory of Open Access Journals (Sweden)

    Arne Astrup

    2013-08-01

    Full Text Available Dietary fibers (DF may affect energy balance, an effect often ascribed to the viscous nature of some water soluble DF, which affect luminal viscosity and thus multiple physiological processes. We have tested the hypothesis that viscous linseed DF reduce apparent nutrient digestibility, and limit weight gain, in a randomized feeding trial where 60 male, growing, Wistar rats, with an initial weight of ~200 g, were fed different diets (n = 10 per group: low DF control (C, 5% DF from cellulose (5-CEL, CEL + 5% DF from whole (5-WL or ground linseed (5-GL, CEL + 5% DF from linseed DF extract (5-LDF, and CEL + 10% DF from linseed DF extract (10-LDF. Diets were provided ad libitum for 21 days. Feed intake and faecal output were measured during days 17–21. Faecal fat excretion increased with increasing DF content and was highest in the 10-LDF group. Apparent fat digestibility was highest with the C diet (94.9% ± 0.8% and lowest (74.3% ± 0.6% with the 10-LDF diet, and decreased in a non-linear manner with increasing DF (p < 0.001. Apparent fat digestibility also decreased with increased accessibility of DF (5-WL vs. 5-GL and when the proportion of viscous DF increased (5-GL vs. 5-LDF. The 10-LDF resulted in a lower final body weight (258 ± 6.2 g compared to C (282 ± 5.9 g, 5-CEL (281 ± 5.9 g, and 5-WL (285 ± 5.9 g (p < 0.05. The 10-LDF diet reduced body fat compared to 5-CEL (p < 0.01. In conclusion, DF extracted from linseed reduced apparent energy and fat digestibility and resulted in restriction of body weight gain in growing rats.

  16. Ginger extract and aerobic training reduces lipid profile in high-fat fed diet rats.

    Science.gov (United States)

    Khosravani, M; Azarbayjani, M A; Abolmaesoomi, M; Yusof, A; Zainal Abidin, N; Rahimi, E; Feizolahi, F; Akbari, M; Seyedjalali, S; Dehghan, F

    2016-04-01

    Obesity, hyperglycemia and dyslipidemia, are major risk factors. However, natural therapies, dietary components, and physical activity may effect on these concerns. The aim of this study was to examine the effect of aerobic exercise and consumption of liquid ginger extract on lipid profile of Male rats with a high-fat fed diet. 32 rats were randomly divided into 4 groups: 1) aerobic exercise, 2) Ginger extract, 3) combined aerobic exercise and Ginger extract, and 4) the control. Subjects of the first three groups received ginger extract via gavage feeding of 250 mg/kg. The exercise program was 3 sessions per week on 3 different days over 4 weeks. Total cholesterol (TC), Triglyceride (TG), HDL and LDL were measured 24-h before the first session and 24-h after the final training session. The concentration of TG in the control group was significantly higher than other groups. In addition, the mean concentration of TG in the aerobic exercise group was significantly lower than Ginger extract group but there was no significant difference as compared to combined aerobic exercise and ginger extract group. The combination of aerobic exercise and ginger consumption significantly reduced the TG level compared to ginger group. TC and LDL concentrations were significantly decreased in all groups compare to control. The combination of aerobic exercise and ginger extract feeding caused a significant increase in HDL levels. The finding of this study suggests that the combination of aerobic exercise and liquid ginger extract consumption might be an effective method of reducing lipid profiles, which will reduce the risk of cardiovascular diseases caused by high-fat diets.

  17. Chlorhexidine-releasing implant coating on intramedullary nail reduces infection in a rat model

    Directory of Open Access Journals (Sweden)

    SM Shiels

    2018-03-01

    Full Text Available The use of internal intramedullary nails for long bone fracture fixation is a common practice among surgeons. Bacteria naturally attach to these devices, increasing the risk for wound infection, which can result in non- or malunion, additional surgical procedures and extended hospital stays. Intramedullary nail surface properties can be modified to reduce bacterial colonisation and potentially infectious complications. In the current study, a coating combining a non-fouling property with leaching chlorhexidine for orthopaedic implantation was tested. Coating stability and chlorhexidine release were evaluated in vitro. Using a rat model of intramedullary fixation and infection, the effect of the coating on microbial colonisation and fracture healing was evaluated in vivo by quantitative microbiology, micro-computed tomography, plain radiography, three-point bending and/or histology. Low dose systemic cefazolin was administered to increase the similarities to clinical practice, without overshadowing the effect of the anti-infective coating. When introduced into a contaminated wound, the non-fouling chlorhexidine-coated implant reduced the overall bacteria colonisation within the bone and on the implant, reduced the osteolysis and increased the radiographic union, confirming its potential for reducing complications in wounds at high risk of infection. However, when implanted into a sterile wound, non-union increased. Further studies are required to best optimise the anti-microbial effectiveness, while not sacrificing fracture union.

  18. Extract of Lycopus europaeus L. reduces cardiac signs of hyperthyroidism in rats.

    Science.gov (United States)

    Vonhoff, Christian; Baumgartner, Andreas; Hegger, Mirjam; Korte, Brigitte; Biller, Andreas; Winterhoff, Hilke

    2006-02-02

    Extracts from the plant Lycopus europaeus L. are traditionally used in mild forms of hyperthyroidism. High doses caused a reduction of TSH or thyroid hormone levels in animal experiments, whereas in hyperthyroid patients treated with low doses of Lycopus an improvement of cardiac symptoms was reported without major changes in TSH or thyroid hormone concentrations. Lycopus extract was tested in thyroxine treated hyperthyroid rats (0.7 mg/kg BW i.p.). Co-treatment with an hydroethanolic extract from L. europaeus L. started one week later than T4-application and lasted 5.5 weeks. As reference substance atenolol was used. The raised body temperature was reduced very effectively even by the low dose of the plant extract, whereas the reduced gain of body weight and the increased food intake remained unaffected by any treatment. No significant changes of thyroid hormone concentrations or TSH levels were observed. Lycopus extract and atenolol reduced the increased heart rate and blood pressure. The cardiac hypertrophy was alleviated significantly by both treatment regimes. beta-Adrenoceptor density in heart tissue was significantly reduced by the Lycopus extract or the beta-blocking agent showing an almost equal efficacy. Although the mode of action remains unclear, these organo-specific anti-T4-effects seem to be of practical interest, for example in patients with latent hyperthyroidism.

  19. Prolonged hydrocephalus induced by intraventricular hemorrhage in rats is reduced by curcumin therapy.

    Science.gov (United States)

    Qi, Zhihua; Zhang, Huiqin; Fu, Chuhua; Liu, Xiao; Chen, Bo; Dang, Yanwei; Chen, Huayun; Liu, Lijun

    2017-01-10

    Prolonged hydrocephalus is a major cause of severe disability and death of intraventricular hemorrhage (IVH) patients. However, the therapeutic options to minimize the detrimental effects of post-hemorrhagic hydrocephalus are limited. Curcumin has been reported to confer neuroprotective effects in numerous neurological diseases and injuries, but its role in IVH-induced hydrocephalus has not been determined. The aim of present study was to determine whether curcumin treatment ameliorates blood brain barrier (BBB) damage and reduces the incidence of post-hemorrhagic hydrocephalus in IVH rat model. Autologous blood intraventricular injection was used to establish the IVH model. Our results revealed that repeated intraperitoneal injection of curcumin ameliorated IVH-induced learning and memory deficits as determined by Morris water maze and reduced the incidence of post-hemorrhagic hydrocephalus in a dose-dependent manner at 28 d post-IVH induction. Further, the increased BBB permeability and brain edema induced by IVH were significantly reduced by curcumin administration. In summary, these findings highlighted the important role of curcumin in improving neurological function deficits and protecting against BBB disruption via promoting the neurovascular unit restoration, and thus it reduced the severity of post-hemorrhagic hydrocephalus in the long term. It is believed that curcumin might prove to be an effective therapeutic component in prevent the post-IVH hydrocephalus in the near future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Intracerebroventricular C75 decreases meal frequency and reduces AgRP gene expression in rats.

    Science.gov (United States)

    Aja, Susan; Bi, Sheng; Knipp, Susan B; McFadden, Jill M; Ronnett, Gabriele V; Kuhajda, Francis P; Moran, Timothy H

    2006-07-01

    3-Carboxy-4-alkyl-2-methylenebutyrolactone (C75), an inhibitor of fatty acid synthase and stimulator of carnitine palmitoyltransferase-1, reduces food intake and body weight in rodents when given systemically or centrally. Intracellular molecular mechanisms involving changes in cellular energy status are proposed to initiate the feeding and body weight reductions. However, effectors that lie downstream of these initial steps are not yet fully identified. Present experiments characterize the time courses of hypophagia and weight loss after single injections of C75 into the lateral cerebroventicle in rats and go on to identify specific meal pattern changes and coinciding alterations in gene expression for feeding-related hypothalamic neuropeptides. C75 reduced chow intake and body weight dose dependently. Although the principal effects occurred on the first day, weight losses relative to vehicle control were maintained over multiple days. C75 did not affect generalized locomotor activity. C75 began to reduce feeding after a 6-h delay. The hypophagia was due primarily to decreased meal number during 6-12 h without a significant effect on meal size, suggesting that central C75 reduced the drive to initiate meals. C75 prevented the anticipated hypophagia-induced increases in mRNA for AgRP in the arcuate nucleus at 22 h and at 6 h when C75 begins to suppress feeding. Overall, the data suggest that gene expression changes leading to altered melanocortin signaling are important for the hypophagic response to intracerebroventricular C75.

  1. Passiflora incarnata L. Improves Spatial Memory, Reduces Stress, and Affects Neurotransmission in Rats.

    Science.gov (United States)

    Jawna-Zboińska, Katarzyna; Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Wawer, Adriana; Pyrzanowska, Justyna; Piechal, Agnieszka; Mirowska-Guzel, Dagmara; Widy-Tyszkiewicz, Ewa

    2016-05-01

    Passiflora incarnata L. has been used as a medicinal plant in South America and Europe since the 16th century. Previous pharmacological studies focused mainly on the plant's sedative, anxiolytic, and anticonvulsant effects on the central nervous system and its supporting role in the treatment of addiction. The aim of the present study was to evaluate the behavioral and neurochemical effects of long-term oral administration of P. incarnata. The passionflower extract (30, 100, or 300 mg/kg body weight/day) was given to 4-week-old male Wistar rats via their drinking water. Tests were conducted after 7 weeks of treatment. Spatial memory was assessed in a water maze, and the levels of amino acids, monoamines, and their metabolites were evaluated in select brain regions by high performance liquid chromatography (HPLC). We observed reduced anxiety and dose-dependent improvement of memory in rats given passionflower compared to the control group. In addition, hippocampal glutamic acid and cortical serotonin content were depleted, with increased levels of metabolites and increased turnover. Thus, our results partially confirmed the proposed mechanism of action of P. incarnata involving GABAA receptors. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

    Science.gov (United States)

    Pinsky, C; Dua, A K; LaBella, F S

    1982-07-15

    Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

  3. Prenatal ethanol exposure reduces the effects of excitatory amino acids in the rat hippocampus

    International Nuclear Information System (INIS)

    Noble, E.P.; Ritchie, T.

    1989-01-01

    Chronic alcohol ingestion during pregnancy can lead to the Fetal Alcohol Syndrome (FAS), a disorder marked by learning disabilities. A rat model of FAS was used by introducing pregnant Sprague-Dawley rats to a liquid diet containing 35% ethanol-derived calories (E), while a second group was pair-fed an isocaloric liquid diet without ethanol (P). A third group of pregnant dams received ad libitum lab chow (C). At parturition, pups from the E and P groups were cross fostered by C mothers and all groups received lab chow. During adulthood, male offspring were sacrificed and hippocampal and prefrontal cortical slices were prelabeled with [3H]inositol. Phosphoinositide (PI) hydrolysis was determined by measuring the accumulation of [3H]inositol phosphates in the presence of LiCl in response to activation of various excitatory amino acid (EAA) receptors. In hippocampal slices, ibotenate- and quisqualate-induced PI hydrolysis was reduced in E compared to P and C animals. Moreover, the inhibitory effect of N-methyl-D-aspartate (NMDA) on carbachol-induced PI hydrolysis, evident in P and C animals, was completely abolished in the hippocampus of E animals. In contrast, in the prefrontal cerebral cortex, this inhibitory effect of NMDA prevailed even in the E animals. The evidence suggests that prenatal ethanol exposure alters the activity of EAA receptors in the hippocampal generation of 2nd messengers

  4. Synbiotic loaded chitosan-Ca-alginate microparticles reduces inflammation in the TNBS model of rat colitis.

    Science.gov (United States)

    Ivanovska, Tanja Petreska; Mladenovska, Kristina; Zhivikj, Zoran; Pavlova, Maja Jurhar; Gjurovski, Ivica; Ristoski, Trpe; Petrushevska-Tozi, Lidija

    2017-07-15

    New therapeutic strategies against inflammatory bowel disease (IBD) consider the usage of probiotics, prebiotics and synbiotics as beneficial for the intestinal microbial balance. Limitations of such an approach are addressed into difference in survival, persistence, colonization and variable effects among different probiotic strains, lack in understanding of probiotic mechanisms of action, as well the complex etiology of IBD. The anti-inflammatory activity of Lactobacillus casei 01 (L. casei 01) was assessed in trinitrobenzenesulphonic (TNBS) acid model of rat colitis when the probiotic was used alone and/or in combination with oligofructose-enriched inulin (Synergy 1), and as synbiotic (L. casei 01+Synergy 1) loaded chitosan-Ca-alginate microparticles; all suspended in ayran. The results from the probiotic/synbiotic treatments (8.5-8.9log CFU g -1 L. casei 01 and 1.5% Synergy 1) have shown reduction in the colonic damage and increased lactobacilli counts in feces. Lactobacilli translocation to sterile extra-intestinal organs demonstrated acceptable safety of the probiotic strain used. The best effect at reducing inflammation and lesions associated with a significant decline in myeloperoxidase (MPO) activity was observed in rats that received synbiotic microparticles. This finding suggests colon targeted delivery of the probiotics/synbiotics, as an advantageous approach in prevention and treatment of IBD. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Melatonin treatment reduces astrogliosis and apoptosis in rats with traumatic brain injury

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    Abdolreza Babaee

    2015-09-01

    Full Text Available Objective(s:Melatonin is known as an anti-inflammatory agent, and it has been proven to exert neuroprotection through inhibition of cell death (apoptosis in several models of brain injury.Secondary injury following the primary traumatic brain injury (TBI results in glial cells activation, especially astrocytes. In fact, astrocyte activation causes the production of pro-inflammatory cytokines that may lead to secondary injury. Since most TBI research studies have focused on injured neurons and paid little attention to glial cells, the aim of current study was to investigate the effects of melatonin against astrocytes activation (astrogliosis, as well as inhibition of apoptosis in brain tissue of male rats after TBI. Materials and Methods: The animals were randomly allocated into five groups: sham group, TBI+ vehicle group (1% ethanol in saline and TBI+ melatonin groups (5 mg/kg, 10 mg/kg and 20 mg/kg. All rats were intubated and then exposed to diffuse TBI, except for the sham group. Immunohistochemical methods were conducted using glial fibrillary acidic protein (GFAP marker and TUNEL assay to evaluate astrocyte reactivity and cell death, respectively. Results: The results showed that based on the number of GFAP positive astrocytes in brain cortex, astrogliosis was reduced significantly (P

  6. Aldosterone Blockade Reduces Mortality without Changing Cardiac Remodeling in Spontaneously Hypertensive Rats

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    Marcelo D.M. Cezar

    2013-11-01

    Full Text Available Background: The role of aldosterone blockers during transition from long-term compensated hypertrophy to dilated failure is not completely understood. In this study we evaluated the effects of early administration of spironolactone on cardiac remodeling, myocardial function, and mortality in spontaneously hypertensive rats (SHR. Methods: Sixteen-month-old SHR received no treatment (SHR-C, n=72 or spironolactone (SHR-SPR, 20 mg/kg/day, n=34 for six months. Echocardiogram was performed before and after treatment. Myocardial function was analyzed in left ventricular (LV papillary muscle preparations. Myocardial collagen and hydroxyproline concentration were evaluated by morphometry and spectrophotometry, respectively. LV gene expression was assessed by real time RT-PCR. Statistics: Student's t test; Log rank test (Kaplan Meyer. Results: SHR-C and SHR-SPR presented mortality rates of 71 and 38%, respectively (p=0.004. Systolic arterial pressure did not differ between groups (SHR-C 199±43; SHR-SPR 200±35 mmHg. Initial and final echocardiograms did not show significant differences in cardiac structures or LV function between groups. Myocardial function was similar between groups at basal and after inotropic stimulation. Collagen fractional area, hydroxyproline concentration, gene expression for α- and β-myosin heavy chain, atrial natriuretic peptide, and Serca2a were not different between groups. Conclusion: Early spironolactone administration reduces mortality without changing cardiac remodeling in spontaneous hypertensive rats.

  7. Tiaolipiwei Acupuncture Reduces Albuminuria by Alleviating Podocyte Lesions in a Rat Model of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Zhilong Zhang

    2018-01-01

    Full Text Available Background. Diabetic nephropathy is a common and serious complication of diabetes and a major cause of end-stage renal disease. Tiaolipiwei acupuncture is a safe treatment approach that may be effective for lowering albuminuria in diabetic nephropathy. Yet, the exact mechanisms of this therapeutic effect are unclear. Methods. A rodent model of type 2 diabetic nephropathy (T2DN was induced by a high-fat diet combined with low-dose streptozotocin. T2DN rats were treated with Tiaolipiwei acupuncture (ACU for 4, 8, or 12 weeks. At the end of treatment, urinary and blood samples were collected for analysis. Transmission electron microscopy was used to observe morphological changes, and protein expression levels of nephrin, CD2AP, podocalyxin, and desmin were quantified in renal tissue. Results. Compared to the T2DN groups, the T2DN + ACU groups showed significant improvements in 24-hour urinary protein, serum urea, cholesterol, and triglycerides at all time points. ACU treatment also improved the density of slit diaphragms. Simultaneously, ACU promoted the renal expression of nephrin, CD2AP, and podocalyxin and decreased the expression of desmin. Conclusion. Our study suggests that Tiaolipiwei acupuncture ameliorates podocyte lesions to reduce albuminuria and prevent the progression of T2DN in a rat model.

  8. Nerve growth factor reduces apoptotic cell death in rat facial motor neurons after facial nerve injury.

    Science.gov (United States)

    Hui, Lian; Yuan, Jing; Ren, Zhong; Jiang, Xuejun

    2015-01-01

    To assess the effects of nerve growth factor (NGF) on motor neurons after induction of a facial nerve lesion, and to compare the effects of different routes of NGF injection on motor neuron survival. This study was carried out in the Department of Otolaryngology Head & Neck Surgery, China Medical University, Liaoning, China from October 2012 to March 2013. Male Wistar rats (n = 65) were randomly assigned into 4 groups: A) healthy controls; B) facial nerve lesion model + normal saline injection; C) facial nerve lesion model + NGF injection through the stylomastoid foramen; D) facial nerve lesion model + intraperitoneal injection of NGF. Apoptotic cell death was detected using the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. Expression of caspase-3 and p53 up-regulated modulator of apoptosis (PUMA) was determined by immunohistochemistry. Injection of NGF significantly reduced cell apoptosis, and also greatly decreased caspase-3 and PUMA expression in injured motor neurons. Group C exhibited better efficacy for preventing cellular apoptosis and decreasing caspase-3 and PUMA expression compared with group D (pfacial nerve injury in rats. The NGF injected through the stylomastoid foramen demonstrated better protective efficacy than when injected intraperitoneally.

  9. Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans.

    Science.gov (United States)

    d'Alessio, Patrizia A; Ostan, Rita; Bisson, Jean-François; Schulzke, Joerg D; Ursini, Matilde V; Béné, Marie C

    2013-07-10

    To further explore the anti-inflammatory properties of d-Limonene. A rat model was used to compare evolution of TNBS (2,5,6-trinitrobenzene sulfonic acid)-induced colitis after oral feeding with d-Limonene compared to ibuprofen. Peripheral levels of TNF-α (Tumor Necrosis Factor alpha) were assessed in all animals. Cell cultures of fibroblasts and enterocytes were used to test the effect of d-Limonene respectively on TNFα-induced NF-κB (nuclear factor-kappa B) translocation and epithelial resistance. Finally, plasmatic inflammatory markers were examined in an observational study of diet supplementation with d-Limonene-containing orange peel extract (OPE) in humans. Administered per os at a dose of 10mg/kg p.o., d-Limonene induced a significant reduction of intestinal inflammatory scores, comparable to that induced by ibuprofen. Moreover, d-Limonene-fed rats had significantly lowered serum concentrations of TNF-α compared to untreated TNBS-colitis rats. The anti-inflammatory effect of d-Limonene also involved inhibition of TNFα-induced NF-κB translocation in fibroblast cultures. The application of d-Limonene on colonic HT-29/B6 cell monolayers increased epithelial resistance. Finally, inflammatory markers, especially peripheral IL-6, markedly decreased upon OPE supplementation of elderly healthy subjects submitted or not to 56 days of dietary supplementation with OPE. In conclusion, d-Limonene indeed demonstrates significant anti-inflammatory effects both in vivo and in vitro. Protective effects on the epithelial barrier and decreased cytokines are involved, suggesting a beneficial role of d-Limonene as diet supplement in reducing inflammation. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardium

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    D.V. Vassallo

    2008-09-01

    Full Text Available Lead (Pb2+ poisoning causes hypertension, but little is known regarding its acute effects on cardiac contractility. To evaluate these effects, force was measured in right ventricular strips that were contracting isometrically in 45 male Wistar rats (250-300 g before and after the addition of increasing concentrations of lead acetate (3, 7, 10, 30, 70, 100, and 300 µM to the bath. Changes in rate of stimulation (0.1-1.5 Hz, relative potentiation after pauses of 15, 30, and 60 s, effect of Ca2+ concentration (0.62, 1.25, and 2.5 mM, and the effect of isoproterenol (20 ng/mL were determined before and after the addition of 100 µM Pb2+. Effects on contractile proteins were evaluated after caffeine treatment using tetanic stimulation (10 Hz and measuring the activity of the myosin ATPase. Pb2+ produced concentration-dependent force reduction, significant at concentrations greater than 30 µM. The force developed in response to increasing rates of stimulation became smaller at 0.5 and 0.8 Hz. Relative potentiation increased after 100 µM Pb2+ treatment. Extracellular Ca2+ increment and isoproterenol administration increased force development but after 100 µM Pb2+ treatment the force was significantly reduced suggesting an effect of the metal on the sarcolemmal Ca2+ influx. Concentration of 100 µM Pb2+ also reduced the peak and plateau force of tetanic contractions and reduced the activity of the myosin ATPase. Results showed that acute Pb2+ administration, although not affecting the sarcoplasmic reticulum activity, produces a concentration-dependent negative inotropic effect and reduces myosin ATPase activity. Results suggest that acute lead administration reduced myocardial contractility by reducing sarcolemmal calcium influx and the myosin ATPase activity. These results also suggest that lead exposure is hazardous and has toxicological consequences affecting cardiac muscle.

  11. Lactate per se improves the excitability of depolarized rat skeletal muscle by reducing the Cl- conductance

    DEFF Research Database (Denmark)

    de Paoli, Frank Vincenzo; Ørtenblad, Niels; Pedersen, Thomas Holm

    2010-01-01

    Studies on rats have shown that lactic acid can improve excitability and function of depolarized muscles. The effect has been related to the ensuing reduction in intracellular pH causing inhibition of muscle fibre Cl- channels. Since, however, several carboxylic acids with structural similarities...... to lactate can inhibit muscle Cl- channels it is possible that lactate per se can increase muscle excitability by exerting a direct effect on these channels. We therefore examined effects of lactate on the function of intact muscles and skinned fibres together with effects on pH and Cl- conductance....... In muscles where extracellular compound action potentials (M-waves) and tetanic force response to excitation were reduced by 82±4 and 83±2 %, respectively, by depolarization with 11 mM extracellular K+, both M-waves and force exhibited an up to 4-fold increase when 20 mM lactate was added. This effect...

  12. Betaine reduces hepatic lipidosis induced by carbon tetrachloride in Sprague-Dawley rats.

    Science.gov (United States)

    Junnila, M; Barak, A J; Beckenhauer, H C; Rahko, T

    1998-10-01

    Carbon tetrachloride-injected rats were given liquid diets with and without betaine for 7 d. Hepatic lipidosis was induced by 4 daily injections of carbon tetrachloride (CCl4). Animals were killed and their livers and blood taken for analysis of betaine, S-adenosylmethionine (SAM), betaine homocysteine methyltransferase (BHMT), triglyceride, alanine aminotransferase and aspartate aminotransferase. Liver samples were also processed and stained for histological examination. Supplemental betaine reduced triglyceride in the liver and centrilobular hepatic lipidosis induced by the CCl4 injections. In both the control and experimental groups receiving betaine, liver betaine, BHMT and SAM were significantly higher than in their respective groups not receiving betaine. This study provides evidence that betaine protects the liver against CCl4-induced lipidosis and may be a useful therapeutic and prophylactic agent in ameliorating the harmful effects of CCl4.

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

    Science.gov (United States)

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

    2011-10-01

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

  14. EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters

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    M Axelstad

    2018-01-01

    Full Text Available Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we examined the effects of early exposure to the painkiller paracetamol and mixtures of human relevant endocrine-disrupting chemicals in rats. One mixture contained four estrogenic compounds; another contained eight anti-androgenic environmental chemicals and a third mixture contained estrogens, anti-androgens and paracetamol. All exposures were administered by oral gavage to time-mated Wistar dams rats (n = 16–20 throughout gestation and lactation. In the postnatal period, testicular histology was affected by the total mixture, and at the end of weaning, male testis weights were significantly increased by paracetamol and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10  months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant women to paracetamol as well as environmental endocrine disrupters.

  15. Strontium ranelate improved tooth anchorage and reduced root resorption in orthodontic treatment of rats.

    Science.gov (United States)

    Kirschneck, Christian; Wolf, Michael; Reicheneder, Claudia; Wahlmann, Ulrich; Proff, Peter; Roemer, Piero

    2014-12-05

    The anchorage mechanisms currently used in orthodontic treatment have various disadvantages. The objective of this study was to determine the applicability of the osteoporosis medication strontium ranelate in pharmacologically induced orthodontic tooth anchorage. In 48 male Wistar rats, a constant orthodontic force of 0.25 N was reciprocally applied to the upper first molar and the incisors by means of a Sentalloy(®) closed coil spring for two to four weeks. 50% of the animals received strontium ranelate at a daily oral dosage of 900 mg per kilogramme of body weight. Bioavailability was determined by blood analyses. The extent of tooth movement was measured both optometrically and cephalometrically (CBCT). Relative alveolar gene expression of osteoclastic markers and OPG-RANKL was assessed by qRT-PCR and root resorption area and osteoclastic activity were determined in TRAP-stained histologic sections of the alveolar process. Compared to controls, the animals treated with strontium ranelate showed up to 40% less tooth movement after four weeks of orthodontic treatment. Gene expression and histologic analyses showed significantly less osteoclastic activity and a significantly smaller root resorption area. Blood analyses confirmed sufficient bioavailability of strontium ranelate. Because of its pharmacologic effects on bone metabolism, strontium ranelate significantly reduced tooth movement and root resorption in orthodontic treatment of rats. Strontium ranelate may be a viable agent for inducing tooth anchorage and reducing undesired root resorption in orthodontic treatment. Patients under medication of strontium ranelate have to expect prolonged orthodontic treatment times. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Ebselen alters mitochondrial physiology and reduces viability of rat hippocampal astrocytes.

    Science.gov (United States)

    Santofimia-Castaño, Patricia; Salido, Ginés M; González, Antonio

    2013-04-01

    The seleno-organic compound and radical scavenger ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) have been extensively employed as an anti-inflammatory and neuroprotective compound. However, its glutathione peroxidase activity at the expense of cellular thiols groups could underlie certain deleterious actions of the compound on cell physiology. In this study, we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular viability, the intracellular free-Ca(2+) concentration ([Ca(2+)]c), the mitochondrial free-Ca(2+) concentration ([Ca(2+)]m), and mitochondrial membrane potential (ψm) were analyzed. The caspase-3 activity was also assayed. Our results show that cell viability was reduced by treatment of cells with ebselen, depending on the concentration employed. In the presence of ebselen, we observed an initial transient increase in [Ca(2+)]c that was then followed by a progressive increase to an elevated plateau. We also observed a transient increase in [Ca(2+)]m in the presence of ebselen that returned toward a value over the prestimulation level. The compound induced depolarization of ψm and altered the permeability of the mitochondrial membrane. Additionally, a disruption of the mitochondrial network was observed. Finally, we did not detect changes in caspase-3 activation in response to ebselen treatment. Collectively, these data support the likelihood of ebselen, depending on the concentration employed, reduces viability of rat hippocampal astrocytes via its action on the mitochondrial activity. These may be early effects that do not involve caspase-3 activation. We conclude that, depending on the concentration used, ebselen might exert deleterious actions on astrocyte physiology that could compromise cell function.

  17. Fructo-oligosaccharides reduce energy intake but do not affect adiposity in rats fed a low-fat diet but increase energy intake and reduce fat mass in rats fed a high-fat diet.

    Science.gov (United States)

    Hadri, Zouheyr; Rasoamanana, Rojo; Fromentin, Gilles; Azzout-Marniche, Dalila; Even, Patrick C; Gaudichon, Claire; Darcel, Nicolas; Bouras, Abdelkader Dilmi; Tomé, Daniel; Chaumontet, Catherine

    2017-12-01

    The ingestion of low or high lipid diets enriched with fructo-oligosaccharide (FOS) affects energy homeostasis. Ingesting protein diets also induces a depression of energy intake and decreases body weight. The goal of this study was to investigate the ability of FOS, combined or not with a high level of protein (P), to affect energy intake and body composition when included in diets containing different levels of lipids (L). We performed two studies of similar design over a period of 5weeks. During the first experiment (exp1), after a 3-week period of adaptation to a normal protein-low fat diet, the rats received one of the following four diets for 5weeks (6 rats per group): (i) normal protein (14% P/E (Energy) low fat (10% L/E) diet, (ii) normal protein, low fat diet supplemented with 10% FOS, (iii) high protein (55%P/E) low fat diet, and (iv) high protein, low fat diet supplemented with 10% FOS. In a second experiment (exp2) after the 3-week period of adaptation to a normal protein-high fat diet, the rats received one of the following 4 diets for 5weeks (6 rats per group): (i) normal protein, high fat diet (35% of fat), (ii) normal protein, high fat diet supplemented with 10% FOS, (iii) high protein high fat diet and (iv) high protein high fat diet supplemented with 10% FOS. In low-fat fed rats, FOS did not affect lean body mass (LBM) and fat mass but the protein level reduced fat mass and tended to reduce adiposity. In high-fat fed rats, FOS did not affect LBM but reduced fat mass and adiposity. No additive or antagonistic effects between FOS and the protein level were observed. FOS reduced energy intake in low-fat fed rats, did not affect energy intake in normal-protein high-fat fed rats but surprisingly, and significantly, increased energy intake in high-protein high-fat fed rats. The results thus showed that FOS added to a high-fat diet reduced body fat and body adiposity. Published by Elsevier Inc.

  18. Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat

    International Nuclear Information System (INIS)

    Piteau, Shalea; Olver, Amy; Kim, Su-Jin; Winter, Kyle; Pospisilik, John Andrew; Lynn, Francis; Manhart, Susanne; Demuth, Hans-Ulrich; Speck, Madeleine; Pederson, Raymond A.; McIntosh, Christopher H.S.

    2007-01-01

    In type 2 diabetes (T2DM) β-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is reduced. In a model of T2DM, the VDF Zucker rat, GIP receptor mRNA and protein levels were shown to be down-regulated. Possible restoration of responsiveness to GIP in Zucker rats by reducing hyperglycemia has been examined. ZDF rats with extreme hyperglycemia demonstrated greater islet GIP receptor mRNA down-regulation (94.3 ± 3.8%) than ZF rats (48.8 ± 22.8%). GIP receptor mRNA levels in ZDF rats returned to 83.0 ± 17.9% of lean following normalization of hyperglycemia by phlorizin treatment and pancreas perfusions demonstrated markedly improved GIP responsiveness. Treatment of VDF rats with a DP IV inhibitor (P32/98) resulted in improved glucose tolerance and restored sensitivity to GIP in isolated pancreata. These findings support the proposal that GIP receptor down-regulation in rodent T2DM is secondary to chronic hyperglycemia and that normalization of glycemia can restore GIP sensitivity

  19. Glycyl-glutamine in nucleus accumbens reduces ethanol intake in alcohol preferring (P) rats.

    Science.gov (United States)

    Resch, Garth E; Shridharani, Shyam; Millington, William R; Garris, David R; Simpson, C Wayne

    2005-10-05

    Opioid peptides and glycyl-glutamine (Gly-Gln) have been implicated in the control of ethanol consumption. A recognized beta-endorphin cleavage product, Gly-Gln, inhibits voluntary alcohol consumption when microinjected into the nucleus accumbens (AcbSh) of P rats. To evaluate the site-specific efficacy of Gly-Gln on ethanol consumption following AcbSh application, ethanol preferring (P) rats were allowed to establish individual baseline ethanol/water consumption utilizing a voluntary self-administration paradigm. Subsequent to baseline ethanol consumption being established, bilateral guide cannulae were stereotaxically implanted +1 mm dorsal to the AcbSh for subsequent Gly-Gln (100 nmol/microl) or saline vehicle (1 microl) injections. Alcohol intake, body weight, and water intake were measured at 24 h post-injection intervals. Unilateral Gly-Gln injections reduced ethanol consumption 35.6% (P < 0.05) from pre-established baseline consumption (6.24 +/- 0.64 g/kg to 4.06 +/- 0.28 g/kg). Bilateral Gly-Gln injections further reduced consumption to 51.9% (6.4 +/- 1.0 g/kg to 3.08 +/- 0.65 g/kg at 24 h (P < 0.01) below established baseline values within 24 h without significant changes in body weight or water consumption. Also, the amino acid constituents of the dipeptide had no influence on ethanol consumption behavior; however, Gly-Gln efficacy was shown to be comparable to central beta-endorphin-(1-27) or intraperitoneal (i.p.) naltrexone-induced suppression of ethanol intake. These data indicate that the AcbSh exhibits a site-specific sensitivity to the suppressive actions of Gly-Gln or beta-endorphin-(1-27) injections that modulate voluntary ethanol consumption in P rats. These findings support the broader concept that select forebrain opioid-responsive neural sites may influence the development or expression of alcohol abuse syndromes in animal models or humans.

  20. Dehydration-Induced Anorexia Reduces Astrocyte Density in the Rat Corpus Callosum

    Directory of Open Access Journals (Sweden)

    Daniel Reyes-Haro

    2015-01-01

    Full Text Available Anorexia nervosa is an eating disorder associated with severe weight loss as a consequence of voluntary food intake avoidance. Animal models such as dehydration-induced anorexia (DIA mimic core features of the disorder, including voluntary reduction in food intake, which compromises the supply of energy to the brain. Glial cells, the major population of nerve cells in the central nervous system, play a crucial role in supplying energy to the neurons. The corpus callosum (CC is the largest white matter tract in mammals, and more than 99% of the cell somata correspond to glial cells in rodents. Whether glial cell density is altered in anorexia is unknown. Thus, the aim of this study was to estimate glial cell density in the three main regions of the CC (genu, body, and splenium in a murine model of DIA. The astrocyte density was significantly reduced (~34% for the DIA group in the body of the CC, whereas in the genu and the splenium no significant changes were observed. DIA and forced food restriction (FFR also reduced the ratio of astrocytes to glial cells by 57.5% and 22%, respectively, in the body of CC. Thus, we conclude that DIA reduces astrocyte density only in the body of the rat CC.

  1. 3',4'-Dihydroxyflavonol reduces superoxide and improves nitric oxide function in diabetic rat mesenteric arteries.

    Directory of Open Access Journals (Sweden)

    Chen-Huei Leo

    Full Text Available 3',4'-Dihydroxyflavonol (DiOHF is an effective antioxidant that acutely preserves nitric oxide (NO activity in the presence of elevated reactive oxygen species (ROS. We hypothesized that DiOHF treatment (7 days, 1 mg/kg per day s.c. would improve relaxation in mesenteric arteries from diabetic rats where endothelial dysfunction is associated with elevated oxidant stress.In mesenteric arteries from diabetic rats there was an increase in ROS, measured by L-012 and 2',7'-dichlorodihydrofluorescein diacetate fluorescence. NADPH oxidase-derived superoxide levels, assayed by lucigenin chemiluminescence, were also significantly increased in diabetic mesenteric arteries (diabetes, 4892±946 counts/mg versus normal 2486±344 counts/mg, n = 7-10, p<0.01 associated with an increase in Nox2 expression but DiOHF (2094±300 counts/mg, n = 10, p<0.001 reversed that effect. Acetylcholine (ACh-induced relaxation of mesenteric arteries was assessed using wire myography (pEC(50 = 7.94±0.13 n = 12. Diabetes significantly reduced the sensitivity to ACh and treatment with DiOHF prevented endothelial dysfunction (pEC(50, diabetic 6.86±0.12 versus diabetic+DiOHF, 7.49±0.13, n = 11, p<0.01. The contribution of NO versus endothelium-derived hyperpolarizing factor (EDHF to ACh-induced relaxation was assessed by evaluating responses in the presence of TRAM-34+apamin+iberiotoxin or N-nitro-L-arginine+ODQ respectively. Diabetes impaired the contribution of both NO (maximum relaxation, R(max diabetic 24±7 versus normal, 68±10, n = 9-10, p<0.01 and EDHF (pEC(50, diabetic 6.63±0.15 versus normal, 7.14±0.12, n = 10-11, p<0.01 to endothelium-dependent relaxation. DiOHF treatment did not significantly affect the EDHF contribution but enhanced NO-mediated relaxation (R(max 69±6, n = 11, p<0.01. Western blotting demonstrated that diabetes also decreased expression and increased uncoupling of endothelial NO synthase (eNOS. Treatment of the

  2. Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.

    Science.gov (United States)

    Modi, Hiren R; Ma, Kaizong; Chang, Lisa; Chen, Mei; Rapoport, Stanley I

    2017-08-01

    Valproic acid (VPA), used for treating bipolar disorder (BD), is teratogenic by inhibiting histone deacetylase. In unanaesthetized rats, chronic VPA, like other mood stabilizers, reduces arachidonic acid (AA) turnover in brain phospholipids, and inhibits AA activation to AA-CoA by recombinant acyl-CoA synthetase-4 (Acsl-4) in vitro. Valnoctamide (VCD), a non-teratogenic constitutional isomer of VPA amide, reported effective in BD, also inhibits recombinant Acsl-4 in vitro. VCD like VPA will reduce brain AA turnover in unanaesthetized rats. A therapeutically relevant (50mg/kg i.p.) dose of VCD or vehicle was administered daily for 30 days to male rats. AA turnover and related parameters were determined using our kinetic model, following intravenous [1- 14 C]AA in unanaesthetized rats for 10min, and measuring labeled and unlabeled lipids in plasma and high-energy microwaved brain. VCD, compared with vehicle, increased λ, the ratio of brain AA-CoA to unesterified plasma AA specific activities; and decreased turnover of AA in individual and total brain phospholipids. VCD's ability like VPA to reduce rat brain AA turnover and inhibit recombinant Acsl-4, and its efficacy in BD, suggest that VCD be further considered as a non-teratogenic VPA substitute for treating BD. Published by Elsevier B.V.

  3. Reduced incidence of stress ulcer in germ-free Sprague Dawley rats.

    Science.gov (United States)

    Paré, W P; Burken, M I; Allen, E D; Kluczynski, J M

    1993-01-01

    Recent findings with respect to the role of spiral gram-negative bacteria in peptic ulcer disease have stimulated interest in discerning the role of these agents in stress ulcer disease. We tested the hypothesis that a standard restraint-cold ulcerogenic procedure would fail to produce ulcers in axenic rats. Axenic, as well as normal Sprague Dawley rats, were exposed to a cold-restraint procedure. The germ-free condition was maintained throughout the study in the axenic rats. Axenic rats had significantly fewer ulcers as compared to normal rats exposed to the standard cold-restraint procedure, as well as handling control rats. The data represent the first report suggesting a microbiologic component in the development of stress ulcer using the rat model.

  4. Reduced pain and inflammation in juvenile and adult rats fed a ketogenic diet.

    Directory of Open Access Journals (Sweden)

    David N Ruskin

    2009-12-01

    Full Text Available The ketogenic diet is a high-fat, low-carbohydrate regimen that forces ketone-based rather than glucose-based cellular metabolism. Clinically, maintenance on a ketogenic diet has been proven effective in treating pediatric epilepsy and type II diabetes, and recent basic research provides evidence that ketogenic strategies offer promise in reducing brain injury. Cellular mechanisms hypothesized to be mobilized by ketone metabolism and underlying the success of ketogenic diet therapy, such as reduced reactive oxygen species and increased central adenosine, suggest that the ketolytic metabolism induced by the diet could reduce pain and inflammation. To test the effects of a ketone-based metabolism on pain and inflammation directly, we fed juvenile and adult rats a control diet (standard rodent chow or ketogenic diet (79% fat ad libitum for 3-4 weeks. We then quantified hindpaw thermal nociception as a pain measure and complete Freund's adjuvant-induced local hindpaw swelling and plasma extravasation (fluid movement from the vasculature as inflammation measures. Independent of age, maintenance on a ketogenic diet reduced the peripheral inflammatory response significantly as measured by paw swelling and plasma extravasation. The ketogenic diet also induced significant thermal hypoalgesia independent of age, shown by increased hindpaw withdrawal latency in the hotplate nociception test. Anti-inflammatory and hypoalgesic diet effects were generally more robust in juveniles. The ketogenic diet elevated plasma ketones similarly in both age groups, but caused slowed body growth only in juveniles. These data suggest that applying a ketogenic diet or exploiting cellular mechanisms associated with ketone-based metabolism offers new therapeutic opportunities for controlling pain and peripheral inflammation, and that such a metabolic strategy may offer significant benefits for children and adults.

  5. Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats

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    Maranhão RC

    2017-05-01

    Full Text Available Raul C Maranhão,1,2 Maria C Guido,1 Aline D de Lima,1 Elaine R Tavares,1 Alyne F Marques,1 Marcelo D Tavares de Melo,3 Jose C Nicolau,3 Vera MC Salemi,3 Roberto Kalil-Filho3 1Laboratory of Metabolism and Lipids, 2Faculty of Pharmaceutical Sciences, 3Heart Failure Unit, Clinical Cardiology Division, Heart Institute (InCor, Medical School Hospital, University of São Paulo, São Paulo, Brazil Purpose: Acute myocardial infarction (MI is accompanied by myocardial inflammation, fibrosis, and ventricular remodeling that, when excessive or not properly regulated, may lead to heart failure. Previously, lipid core nanoparticles (LDE used as carriers of the anti-inflammatory drug methotrexate (MTX produced an 80-fold increase in the cell uptake of MTX. LDE-MTX treatment reduced vessel inflammation and atheromatous lesions induced in rabbits by cholesterol feeding. The aim of the study was to investigate the effects of LDE-MTX on rats with MI, compared with commercial MTX treatment.Materials and methods: Thirty-eight Wistar rats underwent left coronary artery ligation and were treated with LDE-MTX, or with MTX (1 mg/kg intraperitoneally, once/week, starting 24 hours after surgery or with LDE without drug (MI-controls. A sham-surgery group (n=12 was also included. Echocardiography was performed 24 hours and 6 weeks after surgery. The animals were euthanized and their hearts were analyzed for morphometry, protein expression, and confocal microscopy.Results: LDE-MTX treatment achieved a 40% improvement in left ventricular (LV systolic function and reduced cardiac dilation and LV mass, as shown by echocardiography. LDE-MTX reduced the infarction size, myocyte hypertrophy and necrosis, number of inflammatory cells, and myocardial fibrosis, as shown by morphometric analysis. LDE-MTX increased antioxidant enzymes; decreased apoptosis, macrophages, reactive oxygen species production; and tissue hypoxia in non-infarcted myocardium. LDE-MTX increased adenosine

  6. Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons.

    Science.gov (United States)

    Hasan, Wohaib; Smith, Peter G

    2014-04-01

    Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine's role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1h of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24h. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats

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    Liang Shu

    2014-01-01

    Full Text Available Renshaw recurrent inhibition (RI plays an important gated role in spinal motion circuit. Peripheral nerve injury is a common disease in clinic. Our current research was designed to investigate the change of the recurrent inhibitory function in the spinal cord after the peripheral nerve crush injury in neonatal rat. Sciatic nerve crush was performed on 5-day-old rat puppies and the recurrent inhibition between lateral gastrocnemius-soleus (LG-S and medial gastrocnemius (MG motor pools was assessed by conditioning monosynaptic reflexes (MSR elicited from the sectioned dorsal roots and recorded either from the LG-S and MG nerves by antidromic stimulation of the synergist muscle nerve. Our results demonstrated that the MSR recorded from both LG-S or MG nerves had larger amplitude and longer latency after neonatal sciatic nerve crush. The RI in both LG-S and MG motoneuron pools was significantly reduced to virtual loss (15–20% of the normal RI size even after a long recovery period upto 30 weeks after nerve crush. Further, the degree of the RI reduction after tibial nerve crush was much less than that after sciatic nerve crush indicatig that the neuron-muscle disconnection time is vital to the recovery of the spinal neuronal circuit function during reinnervation. In addition, sciatic nerve crush injury did not cause any spinal motor neuron loss but severally damaged peripheral muscle structure and function. In conclusion, our results suggest that peripheral nerve injury during neonatal early development period would cause a more sever spinal cord inhibitory circuit damage, particularly to the Renshaw recurrent inhibition pathway, which might be the target of neuroregeneration therapy.

  8. Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy.

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    Aude Carillion

    Full Text Available In the diabetic heart the β-adrenergic response is altered partly by down-regulation of the β1-adrenoceptor, reducing its positive inotropic effect and up-regulation of the β3-adrenoceptor, increasing its negative inotropic effect. Statins have clinical benefits on morbidity and mortality in diabetic patients which are attributed to their "pleiotropic" effects. The objective of our study was to investigate the role of statin treatment on β-adrenergic dysfunction in diabetic rat cardiomyocytes.β-adrenergic responses were investigated in vivo (echocardiography and ex vivo (left ventricular papillary muscles in healthy and streptozotocin-induced diabetic rats, who were pre-treated or not by oral atorvastatin over 15 days (50 mg.kg-1.day-1. Micro-array analysis and immunoblotting were performed in left ventricular homogenates. Data are presented as mean percentage of baseline ± SD.Atorvastatin restored the impaired positive inotropic effect of β-adrenergic stimulation in diabetic hearts compared with healthy hearts both in vivo and ex vivo but did not suppress the diastolic dysfunction of diabetes. Atorvastatin changed the RNA expression of 9 genes in the β-adrenergic pathway and corrected the protein expression of β1-adrenoceptor and β1/β3-adrenoceptor ratio, and multidrug resistance protein 4 (MRP4. Nitric oxide synthase (NOS inhibition abolished the beneficial effects of atorvastatin on the β-adrenoceptor response.Atorvastatin restored the positive inotropic effect of the β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by multiple modifications in expression of proteins in the β-adrenergic signaling pathway, particularly through the NOS pathway.

  9. Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy.

    Science.gov (United States)

    Carillion, Aude; Feldman, Sarah; Na, Na; Biais, Matthieu; Carpentier, Wassila; Birenbaum, Aurélie; Cagnard, Nicolas; Loyer, Xavier; Bonnefont-Rousselot, Dominique; Hatem, Stéphane; Riou, Bruno; Amour, Julien

    2017-01-01

    In the diabetic heart the β-adrenergic response is altered partly by down-regulation of the β1-adrenoceptor, reducing its positive inotropic effect and up-regulation of the β3-adrenoceptor, increasing its negative inotropic effect. Statins have clinical benefits on morbidity and mortality in diabetic patients which are attributed to their "pleiotropic" effects. The objective of our study was to investigate the role of statin treatment on β-adrenergic dysfunction in diabetic rat cardiomyocytes. β-adrenergic responses were investigated in vivo (echocardiography) and ex vivo (left ventricular papillary muscles) in healthy and streptozotocin-induced diabetic rats, who were pre-treated or not by oral atorvastatin over 15 days (50 mg.kg-1.day-1). Micro-array analysis and immunoblotting were performed in left ventricular homogenates. Data are presented as mean percentage of baseline ± SD. Atorvastatin restored the impaired positive inotropic effect of β-adrenergic stimulation in diabetic hearts compared with healthy hearts both in vivo and ex vivo but did not suppress the diastolic dysfunction of diabetes. Atorvastatin changed the RNA expression of 9 genes in the β-adrenergic pathway and corrected the protein expression of β1-adrenoceptor and β1/β3-adrenoceptor ratio, and multidrug resistance protein 4 (MRP4). Nitric oxide synthase (NOS) inhibition abolished the beneficial effects of atorvastatin on the β-adrenoceptor response. Atorvastatin restored the positive inotropic effect of the β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by multiple modifications in expression of proteins in the β-adrenergic signaling pathway, particularly through the NOS pathway.

  10. The Protective Effect of Field Mint Leaves in Reducing Stomach Ulcer in Rats Induced by Aspirin

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    Vanitha Ratha Krisnan

    2015-09-01

    Full Text Available Background: Stomach mucosal wall erosion is caused by the imbalance of the aggressive factors and mucosal defensive factors due to the common causes such as the side effect of consuming non-steroidal anti-inflammatory drugs. Field mint (Menthaarvensis leaves have been used as an alternative option to cure and prevent the gastric problems. The aim of this study was to analyze the protective effect of Field mint leaves infusion in reducing stomach ulcer in rats induced by Aspirin. Methods: The experimental study was conducted at Histology Laboratory of Faculty of Medicine, Universitas Padjadjaran, Bandung. Sixteen rats were divided into 4 groups randomly: group I (control negative group, group II (control positive group, given 90mg/day Aspirin, group III (the treatment group, given 5cc of Field mint leaves infusion and 90 mg Aspirin and group IV (the treatment group, given 5.6µg of Misoprostol and 90 mg Aspirin. Mucosal wall erosions were determined by using microscope. Data were analyzed using non-parametric Kruskal-Wallis test and Mann-Whitney U-test (CI 95% and p-value<0.05 Results: Group II had high score of mucosal wall erosions after given only aspirin. In group III and IV, the score of mucosal wall erosions were low. However there was no difference in score of mucosal wall erosions between group III-IV (p<0.05 Conclusions: Field mint (Menthaarvensis leaves infusion is able to prevent stomach mucosal wall erosions induced by Aspirin as misoprostol does.

  11. Reduced sarcoplasmic reticulum content of releasable Ca2+ in rat soleus muscle fibres after eccentric contractions

    DEFF Research Database (Denmark)

    Nielsen, J S; Sahlin, K; Ørtenblad, N

    2007-01-01

    AIM: The purpose was to evaluate the effects of fatiguing eccentric contractions (EC) on calcium (Ca2+) handling properties in mammalian type I muscles. We hypothesized that EC reduces both endogenous sarcoplasmic reticulum (SR) content of releasable Ca2+ (eSRCa2+) and myofibrillar Ca2+ sensitivity....... METHODS: Isolated rat soleus muscles performed 30 EC bouts. Single fibres were isolated from the muscle and after mechanical removal of sarcolemma used to measure eSRCa2+, rate of SR Ca2+ loading and myofibrillar Ca2+ sensitivity. RESULTS: Following EC maximal force in whole muscle was reduced by 30......% and 16/100 Hz force ratio by 33%. The eSRCa2+ in fibres from non-stimulated muscles was 45 +/- 5% of the maximal loading capacity. After EC, eSRCa2+ per fibre CSA decreased by 38% (P = 0.05), and the maximal capacity of SR Ca2+ loading was depressed by 32%. There were no effects of EC on either...

  12. Ceftriaxone pretreatment reduces the propensity of postpartum depression following stroke during pregnancy in rats.

    Science.gov (United States)

    Guan, Yonghong; Liu, Xianying; Su, Yuetian

    2016-10-06

    Ischemic stroke increases the propensity to develop depression in humans and laboratory animals, and we hypothesized that such an incidence during pregnancy may increase the risk for the development of postpartum depression (PPD). To test this hypothesis, we used bilateral common carotid arteries occlusion (BCCAO) to induce transient cerebral ischemia in pregnant rats, and evaluated its effects on subsequent development of PPD in dams. Additionally, we investigated whether ceftriaxone pretreatments before the induction of brain ischemia could alter the propensity of PPD. We found that 15min BCCAO during pregnancy enhanced immobility time and reduced the frequency of swimming or climbing behaviors in the forced swim test, and decreased the sucrose preference in dams at postpartum day 21. Such behavioral alterations were associated with lower level of GLT-1 expression in the medial prefrontal cortical regions (mPFC) of PPD dams. Specifically, mPFC GLT-1 expression levels in dams with ischemia history were correlated with sucrose preference levels at postpartum day 21. Finally, ceftriaxone pretreatment (200mg/kg/day, 5days) before the 15min BCCAO prevented the development of PPD, and prevented the reduction of GLT-1 expression in the mPFC. Taken together, our results suggested that ceftriaxone pretreatment before brain ischemia during pregnancy may reduce the propensity for the development of PPD by preventing the loss of GLT-1 expression in the mPFC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats.

    Science.gov (United States)

    Palmatier, Matthew I; Kellicut, Marissa R; Brianna Sheppard, A; Brown, Russell W; Robinson, Donita L

    2014-11-01

    Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by

  14. Blunted hypothalamic ghrelin signaling reduces diet intake in rats fed a low-protein diet in late pregnancy

    Science.gov (United States)

    Diet intake in pregnant rats fed a low-protein (LP) diet was significantly reduced during late pregnancy despite elevated plasma levels of ghrelin. In this study, we hypothesized that ghrelin signaling in the hypothalamus is blunted under a low-protein diet condition and therefore, it does not stimu...

  15. Phenobarbital reduces blood glucose and gluconeogenesis through down-regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression in rats.

    Science.gov (United States)

    Oda, Hiroaki; Okuda, Yuji; Yoshida, Yukiko; Kimura, Noriko; Kakinuma, Atsushi

    2015-10-23

    The regulatory mechanism of phosphoenolpyruvate carboykinase (GTP) (EC 4.1.1.32) (PEPCK) gene expression and gluconeogenesis by phenobarbital (PB), which is known to induce drug-metabolizing enzymes, was investigated. Higher level of PEPCK mRNA was observed in spherical rat primary hepatocytes on EHS-gel than monolayer hepatocytes on TIC (type I collagen). We found that PB directly suppressed PEPCK gene expression in spherical hepatocytes on EHS-gel, but not in those on TIC. PB strongly suppressed cAMP-dependent induction of PEPCK gene expression. Tyrosine aminotransferase (TAT), another gluconeogenic enzyme, was induced by cAMP, but not suppressed by PB. Chronic administration of PB reduced hepatic PEPCK mRNA in streptozotocin-induced diabetic and nondiabetic rats, and PB reduced blood glucose level in diabetic rats. Increased TAT mRNA in diabetic rats was not suppressed by PB. These results indicated that PB-dependent reduction is specific to PEPCK. From pyrvate challenge test, PB suppressed the increased gluconeogenesis in diabetic rats. PEPCK gene promoter activity was suppressed by PB in HepG2 cells. In conclusion, we found that spherical hepatocytes cultured on EHS-gel are capable to respond to PB to suppress PEPCK gene expression. Moreover, our results indicate that hypoglycemic action of PB result from transcriptional repression of PEPCK gene and subsequent suppression of gluconeogenesis. Copyright © 2015. Published by Elsevier Inc.

  16. Reduced Expression of the Liver/Beta-Cell Glucose Transporter Isoform in Glucose-Insensitive Pancreatic Beta Cells of Diabetic Rats

    Science.gov (United States)

    Thorens, Bernard; Weir, Gordon C.; Leahy, John L.; Lodish, Harvey F.; Bonner-Weir, Susan

    1990-09-01

    Rats injected with a single dose of streptozocin at 2 days of age develop non-insulin-dependent diabetes 6 weeks later. The pancreatic beta islet cells of these diabetic rats display a loss of glucose-induced insulin secretion while maintaining sensitivity to other secretagogues such as arginine. We analyzed the level of expression of the liver/beta-cell glucose transporter isoform in diabetic islets by immunofluorescence staining of pancreas sections and by Western blotting of islet lysates. Islets from diabetic animals have a reduced expression of this beta-cell-specific glucose transporter isoform and the extent of reduction is correlated with the severity of hyperglycemia. In contrast, expression of this transporter isoform in liver is minimally modified by the diabetes. Thus a decreased expression of the liver/beta-cell glucose transporter isoform in beta cells is associated with the impaired glucose sensing characteristic of diabetic islets; our data suggest that this glucose transporter may be part of the beta-cell glucose sensor.

  17. Reduced Incidence of Slowly Progressive Heymann Nephritis in Rats Immunized With a Modified Vaccination Technique

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    Arpad Z. Barabas

    2006-01-01

    Full Text Available A slowly progressive Heymann nephritis (SPHN was induced in three groups of rats by weekly injections of a chemically modified renal tubular antigen in an aqueous medium. A control group of rats received the chemically unmodified version of the antigen in an aqueous solution. One group of SPHN rats were pre- and post-treated with weekly injections of IC made up of rKF3 and rarKF3 IgM antibody at antigen excess (MIC (immune complexes [ICs] containing sonicated ultracentrifuged [u/c] rat kidney fraction 3 [rKF3] antigen and IgM antibodies specific against the antigen, at slight antigen excess. One group of SPHN rats were post-treated with MIC 3 weeks after the induction of the disease and one group of SPHN animals received no treatment. The control group of rats received pre- and post-treatment with sonicated u/c rKF3.

  18. Silymarin and vitamin E reduce amiodarone-induced lysosomal phospholipidosis in rats

    International Nuclear Information System (INIS)

    Agoston, Marta; Oersi, Ferenc; Feher, Erzsebet; Hagymasi, Krisztina; Orosz, Zsuzsa; Blazovics, Anna; Feher, Janos; Vereckei, Andras

    2003-01-01

    Several antioxidants have been shown to reduce lysosomal phospholipidosis, which is a potential mechanism of amiodarone toxicity, and prevent amiodarone toxicity by antioxidant and/or non-antioxidant mechanisms. The aim of this study was to test whether the co-administration of two structurally different antioxidants vitamin E and silymarin with amiodarone can reduce amiodarone-induced lysosomal phospholipidosis, and if yes, by reducing the tissue concentration of amiodarone and desethylamiodarone or by their antioxidant action. To this end, male Fischer 344 rats were treated by gavage once a day for 3 weeks and randomly assigned to the following four experimental groups: 1, control; 2, amiodarone (150 mg/(kg per day)); 3, amiodarone (150 mg/(kg per day)) plus vitamin E (100 mg/(kg per day)); 4, amiodarone (150 mg/(kg per day)) plus silymarin (60 mg/(kg per day)) treated groups. Total plasma phospholipid (PL), liver-conjugated diene, thiobarbituric acid reactive substances (TBARSs), amiodarone and desethylamiodarone concentrations were determined and the extent of lysosomal phospholipidosis in the liver was estimated by a semi-quantitative electron microscopic method. Amiodarone treatment increased significantly the liver-conjugated diene (P<0.001), TBARS (P=0.012), plasma total PL (P<0.001) concentrations compared with control. Antioxidants combined with amiodarone significantly decreased the liver-conjugated diene (P<0.001 for both), TBARS (P=0.016 for vitamin E, P=0.053 borderline for silymarin) and plasma total PL (P=0.058 borderline for vitamin E, P<0.01 for silymarin) concentrations compared with amiodarone treatment alone. Silymarin significantly (P=0.021) reduced liver amiodarone, but only tended to decrease desethylamiodarone concentration; however, vitamin E failed to do so. Amiodarone treatment increased lysosomal phospholipidosis (P<0.001) estimated by semi-quantitative electron microscopic method and both antioxidants combined with amiodarone reduced

  19. Reduced protein oxidation in Wistar rats supplemented with marine ω3 PUFAs.

    Science.gov (United States)

    Méndez, Lucía; Pazos, Manuel; Gallardo, José M; Torres, Josep L; Pérez-Jiménez, Jara; Nogués, Rosa; Romeu, Marta; Medina, Isabel

    2013-02-01

    The potential effects of various dietary eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6) ratios (1:1, 2:1, and 1:2, respectively) on protein redox states from plasma, kidney, skeletal muscle, and liver were investigated in Wistar rats. Dietary fish oil groups were compared with animals fed soybean and linseed oils, vegetable oils enriched in ω6 linoleic acid (LA; 18:2) and ω3 α-linolenic acid (ALA; 18:3), respectively. Fish oil treatments were effective at reducing the level of total fatty acids in plasma and enriching the plasmatic free fatty acid fraction and erythrocyte membranes in EPA and DHA. A proteomic approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labeling of protein carbonyls, FTSC intensity visualization on 1-DE or 2-DE gels, and protein identification by MS/MS was used for the protein oxidation assessment. Albumin was found to be the most carbonylated protein in plasma for all dietary groups, and its oxidation level was significantly modulated by dietary interventions. Supplementation with an equal EPA:DHA ratio (1:1) showed the lowest oxidation score for plasma albumin, followed in increasing order of carbonylation by 1:2 proteins and cytosolic proteins from kidney and liver also indicated a protective effect on proteins for the fish oil treatments, the 1:1 ratio exhibiting the lowest protein oxidation scores. The effect of fish oil treatments at reducing carbonylation on specific proteins from plasma (albumin), skeletal muscle (actin), and liver (albumin, argininosuccinate synthetase, 3-α-hydroxysteroid dehydrogenase) was remarkable. This investigation highlights the efficiency of dietary fish oil at reducing in vivo oxidative damage of proteins compared to oils enriched in the 18-carbon polyunsaturated fatty acids ω3 ALA and ω6 LA, and such antioxidant activity may differ among different fish oil sources because of variations in EPA/DHA content. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Hypothermia Modulates Cytokine Responses After Neonatal Rat Hypoxic-Ischemic Injury and Reduces Brain Damage

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    Xiangpeng Yuan

    2014-11-01

    Full Text Available While hypothermia (HT is the standard-of-care for neonates with hypoxic ischemic injury (HII, the mechanisms underlying its neuroprotective effect are poorly understood. We examined ischemic core/penumbra and cytokine/chemokine evolution in a 10-day-old rat pup model of HII. Pups were treated for 24 hr after HII with HT (32℃; n = 18 or normothermia (NT, 35℃; n = 15. Outcomes included magnetic resonance imaging (MRI, neurobehavioral testing, and brain cytokine/chemokine profiling (0, 24, 48, and 72 hr post-HII. Lesion volumes (24 hr were reduced in HT pups (total 74%, p < .05; penumbra 68%, p < .05; core 85%, p = .19. Lesion volumes rebounded at 72 hr (48 hr post-HT with no significant differences between NT and HT pups. HT reduced interleukin-1β (IL-1β at all time points (p < .05; monocyte chemoattractant protein-1 (MCP-1 trended toward being decreased in HT pups (p = .09. The stem cell signaling molecule, stromal cell-derived factor-1 (SDF-1 was not altered by HT. Our data demonstrate that HT reduces total and penumbral lesion volumes (at 24 and 48 hr, potentially by decreasing IL-1β without affecting SDF-1. Disassociation between the increasing trend in HII volumes from 48 to 72 hr post-HII when IL-1β levels remained low suggests that after rewarming, mechanisms unrelated to IL-1β expression are likely to contribute to this delayed increase in injury. Additional studies should be considered to determine what these mechanisms might be and also to explore whether extending the duration or degree of HT might ameliorate this delayed increase in injury.

  1. Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats.

    Science.gov (United States)

    Turan, Inci; Ozacmak, Hale Sayan; Ozacmak, V Haktan; Barut, Figen; Araslı, Mehmet

    2017-11-15

    Oxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats. Four groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10mg/kg) was administered intraperitoneally before reperfusion period. After 180min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry. The treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-γ, and IL-1α were brought back to the sham control levels by the treatment as well. Our findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Dietary red palm oil supplementation reduces myocardial infarct size in an isolated perfused rat heart model

    Directory of Open Access Journals (Sweden)

    Esterhuyse Adriaan J

    2010-06-01

    Full Text Available Abstract Background and Aims Recent studies have shown that dietary red palm oil (RPO supplementation improves functional recovery following ischaemia/reperfusion in isolated hearts. The main aim of this study was to investigate the effects of dietary RPO supplementation on myocardial infarct size after ischaemia/reperfusion injury. The effects of dietary RPO supplementation on matrix metalloproteinase-2 (MMP2 activation and PKB/Akt phosphorylation were also investigated. Materials and methods Male Wistar rats were divided into three groups and fed a standard rat chow diet (SRC, a SRC supplemented with RPO, or a SRC supplemented with sunflower oil (SFO, for a five week period, respectively. After the feeding period, hearts were excised and perfused on a Langendorff perfusion apparatus. Hearts were subjected to thirty minutes of normothermic global ischaemia and two hours of reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining. Coronary effluent was collected for the first ten minutes of reperfusion in order to measure MMP2 activity by gelatin zymography. Results Dietary RPO-supplementation decreased myocardial infarct size significantly when compared to the SRC-group and the SFO-supplemented group (9.1 ± 1.0% versus 30.2 ± 3.9% and 27.1 ± 2.4% respectively. Both dietary RPO- and SFO-supplementation were able to decrease MMP2 activity when compared to the SRC fed group. PKB/Akt phosphorylation (Thr 308 was found to be significantly higher in the dietary RPO supplemented group when compared to the SFO supplemented group at 10 minutes into reperfusion. There was, however, no significant changes observed in ERK phosphorylation. Conclusions Dietary RPO-supplementation was found to be more effective than SFO-supplementation in reducing myocardial infarct size after ischaemia/reperfusion injury. Both dietary RPO and SFO were able to reduce MMP2 activity, which suggests that MMP2 activity does not play a major role in

  3. Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol-Preferring (P) Rats.

    Science.gov (United States)

    Froehlich, Janice C; Nicholson, Emily R; Dilley, Julian E; Filosa, Nick J; Rademacher, Logan C; Smith, Teal N

    2017-08-01

    Most alcoholics experience periods of voluntary alcohol abstinence or imposed alcohol deprivation followed by a return to alcohol drinking. This study examined whether varenicline (VAR) reduces alcohol intake during a return to drinking after periods of alcohol deprivation in rats selectively bred for high alcohol drinking (the alcohol preferring or "P" rats). Alcohol-experienced P rats were given 24-hour access to food and water and scheduled access to alcohol (15% and 30% v/v) for 2 h/d. After 4 weeks, rats were deprived of alcohol for 2 weeks, followed by reaccess to alcohol for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were fed either vehicle (VEH) or VAR, in doses of 0.5, 1.0, or 2.0 mg/kg BW, at 1 hour prior to onset of the daily alcohol reaccess period for the first 5 days of each of the 3 alcohol reaccess cycles. Low-dose VAR (0.5 mg/kg BW) reduced alcohol intake during the 5 days of drug treatment in alcohol reaccess cycles 1 and 2. Higher doses of VAR (1.0 mg/kg BW and 2.0 mg/kg BW) reduced alcohol intake during the 5 days of treatment in all 3 alcohol reaccess cycles. The decrease in alcohol intake disappeared with termination of VAR treatment in all alcohol reaccess cycles. The results demonstrate that VAR decreases alcohol intake during multiple cycles of alcohol reaccess following alcohol deprivation in rats and suggests that it may prevent a return to heavy alcohol drinking during a lapse from alcohol abstinence in humans with alcohol use disorder. Copyright © 2017 by the Research Society on Alcoholism.

  4. Effect of D-penicillamine on the concentration of reduced glutathione in the liver of irradiated rats

    International Nuclear Information System (INIS)

    Oroszlan, Gyoergy; Buzasi, Edit; Szabo, Terez; Lakatos, Lajos; Karmazsin, Laszlo

    1984-01-01

    Rats received whole-body sup(60)Co-irradiation of 10 Gy total dose with a dose-rate of 0.6 Gy per min. The concentration of reduced glutathione increased upon irradiation; this increase was diminished by D-penicillamine pretreatment in newborn but not in adult rats. The age-dependent effects of D-penicillamine might explain the clinical observation that the frequency of retrolental fibrosis is decreased by D-penicillamine in small-weight pre-term neonates. (L.E.)

  5. Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats

    Directory of Open Access Journals (Sweden)

    Yang Jia-Le

    2012-05-01

    Full Text Available Abstract Background Spinal glia, particularly microglia and astrocytes, are of the utmost importance in the development and maintenance of chronic pain. A recent study from our laboratory revealed that gabapentin, a recommended first-line treatment for multiple neuropathic conditions, could also efficiently antagonize thermal hyperalgesia evoked by complete Freund's adjuvant (CFA-induced monoarthritis (MA. In the present study, we investigated whether the spinal glia are involved in the anti-hyperalgesic effect of gabapentin and how this event occurs. Results Unilateral intra-articular injection of CFA produced a robust activation of microglia and astrocytes. These cells exhibited large cell bodies, thick processes and increases in the ionized calcium binding adapter molecule 1 (Iba-1, a microglial marker or the glia fibrillary acidic protein (GFAP, an astrocytic marker. These cells also displayed immunoreactive signals, and an upregulation of the voltage-gated calcium channels (VGCCs α2/δ-1 subunit, CX3CL1 and CX3CR1 expression levels in the spinal cord. These changes were associated with the development of thermal hyperalgesia. Immunofluorescence staining showed that VGCC α2/δ-1 subunit, a proposed gabapentin target of action, was widely distributed in primary afferent fibers terminals and dorsal horn neurons. CX3CL1, a potential trigger to activate microglia, colocalized with VGCC α2/δ-1 subunits in the spinal dorsal horn. However, its receptor CX3CR1 was mainly expressed in the spinal microglia. Multiple intraperitoneal (i.p. gabapentin injections (100 mg/kg, once daily for 4 days with the first injection 60 min before intra-articular CFA suppressed the activation of spinal microglia, downregulated spinal VGCC α2/δ-1 subunits decreased CX3CL1 levels and blocked the development of thermal hyperalgesia in MA rats. Conclusions Here we provide the first evidence that gabapentin diminishes CX3CL1 signaling and spinal microglia

  6. A new potential AED, carisbamate, substantially reduces spontaneous motor seizures in rats with kainate-induced epilepsy

    Science.gov (United States)

    Grabenstatter, Heidi L.; Dudek, F. Edward

    2010-01-01

    Purpose Animal models with spontaneous epileptic seizures may be useful in the discovery of new antiepileptic drugs (AEDs). The purpose of the present study was to evaluate the efficacy of carisbamate on spontaneous motor seizures in rats with kainate-induced epilepsy. Methods Repeated, low-dose (5 mg/kg), intraperitoneal injections of kainate were administered every hour until each male Sprague-Dawley rat had experienced convulsive status epilepticus for at least 3 h. Five 1-month trials (n= 8–10 rats) assessed the effects of 0.3, 1, 3, 10 and 30 mg/kg carisbamate on spontaneous seizures. Each trial involved six AED-versus-vehicle tests comprised of carisbamate or 10% solutol-HS-15 treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Results Carisbamate significantly reduced motor seizure frequency at doses of 10 and 30 mg/kg, and caused complete seizure cessation during the 6-h post-drug epoch in 7 of 8 animals at 30 mg/kg. The effects of carisbamate (0.3–30 mg/kg) on spontaneous motor seizures appeared dose dependent. Conclusions These data support the hypothesis that a repeated-measures, cross-over protocol in animal models with spontaneous seizures is an effective method for testing AEDs. Carisbamate reduced the frequency of spontaneous motor seizures in a dose-dependent manner, and was more effective than topiramate at reducing seizures in rats with kainate-induced epilepsy. PMID:18494790

  7. Reduced-calorie avocado paste attenuates metabolic factors associated with a hypercholesterolemic-high fructose diet in rats.

    Science.gov (United States)

    Pahua-Ramos, María Elena; Garduño-Siciliano, Leticia; Dorantes-Alvarez, Lidia; Chamorro-Cevallos, German; Herrera-Martínez, Julieta; Osorio-Esquivel, Obed; Ortiz-Moreno, Alicia

    2014-03-01

    The objective of this study was to evaluate the effect of reduced-calorie avocado paste on lipid serum profile, insulin sensitivity, and hepatic steatosis in rats fed a hypercholesterolemic-high fructose diet. Thirty five male Wistar rats were randomly separated in five groups: Control group (ground commercial diet); hypercholesterolemic diet plus 60% fructose solution (HHF group); hypercholesterolemic diet plus 60% fructose solution supplemented with avocado pulp (HHF+A group); hypercholesterolemic diet plus 60% fructose solution supplemented with reduced-calorie avocado paste (HHF+P group); and hypercholesterolemic diet plus 60% fructose solution supplemented with a reduced-calorie avocado paste plus fiber (HHF+FP group). The A, P, and FP were supplemented at 2 g/kg/d. The study was carried out for seven weeks. Rats belonging to the HHF group exhibited significantly (P ≤ 0.05) higher total cholesterol, triglycerides, and insulin levels in serum as well as lower insulin sensitivity than the control group. Supplementation with reduced-calorie avocado paste showed a significant (P ≤ 0.05) decrease in total cholesterol (43.1%), low-density lipoprotein (45.4%), and triglycerides (32.8%) in plasma as well as elevated insulin sensitivity compared to the HHF group. Additionally, the liver enzymes alanine aminotransferase and aspartate aminotransferase decreased significantly in the HHF-P group (39.8 and 35.1%, respectively). These results are likely due to biocompounds present in the reduced-calorie avocado paste, such as polyphenols, carotenoids, chlorophylls, and dietary fibre, which are capable of reducing oxidative stress. Therefore, reduced-calorie avocado paste attenuates the effects of a hypercholesterolemic-high fructose diet in rats.

  8. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle.

    Science.gov (United States)

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-04

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

  9. Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus.

    Science.gov (United States)

    Garcia, Camila Araújo Bernardino; Catalão, Carlos Henrique Rocha; Machado, Hélio Rubens; Júnior, Ivair Matias; Romeiro, Thais Helena; Peixoto-Santos, José Eduardo; Santos, Marcelo Volpon; da Silva Lopes, Luiza

    2017-03-01

    We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus. Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies. The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p  0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group. We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

  10. Hippocampal neuroligin-2 overexpression leads to reduced aggression and inhibited novelty reactivity in rats.

    Directory of Open Access Journals (Sweden)

    Christine Kohl

    Full Text Available Disturbances of the excitation/inhibition (E/I balance in the brain were recently suggested as potential factors underlying disorders like autism and schizophrenia resulting in associated behavioral alterations including changes in social and emotional behavior as well as abnormal aggression. Neuronal cell adhesion molecules (nCAMs and mutations in these genes were found to be strongly implicated in the pathophysiology of these disorders. Neuroligin2 (nlgn2 is a postsynaptic cell adhesion molecule, which is predominantly expressed at inhibitory synapses and required for synapse specification and stabilization. Changes in the expression of nlgn2 were shown to result in alterations of social behavior as well as altered inhibitory synaptic transmission, hence modifying the E/I balance. In our study, we focused on the role of nlgn2 in the dorsal hippocampus in the regulation of emotional and social behaviors. To this purpose, we injected an AAV construct overexpressing nlgn2 in the hippocampus of rats and investigated the effects on behavior and on markers for the E/I ratio. We could show an increase in GAD65, a GABA-synthesizing protein in neuronal terminals, and furthermore, reduced exploration of novel stimuli and less offensive behavior. Our data suggest nlgn2 in the hippocampus to be strongly implicated in maintaining the E/I balance in the brain and thereby modulating social and emotional behavior.

  11. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Boberg, Julie; Vinggaard, Anne Marie

    2013-01-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T4) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gest...

  12. Perinatal L-arginine and antioxidant supplements reduce adult blood pressure in spontaneously hypertensive rats

    NARCIS (Netherlands)

    Racasan, S; Braam, B; van der Giezen, DM; Goldschmeding, R; Boer, P; Koomans, HA; Joles, JA

    Embryo cross-transplantation and cross-fostering between spontaneously hypertensive rats (SHR) and normotensive rats (WKY) suggest that perinatal environment modulates the genetically determined phenotype. In SHR the balance between NO and reactive oxygen species (ROS) is disturbed. We hypothesized

  13. Preliminary Effect of Synthetic Vision Systems Displays to Reduce Low-Visibility Loss of Control and Controlled Flight Into Terrain Accidents

    Science.gov (United States)

    Glaab, Louis J.; Takallu, Mohammad A.

    2002-01-01

    An experimental investigation was conducted to study the effectiveness of Synthetic Vision Systems (SVS) flight displays as a means of eliminating Low Visibility Loss of Control (LVLOC) and Controlled Flight Into Terrain (CFIT) accidents by low time general aviation (GA) pilots. A series of basic maneuvers were performed by 18 subject pilots during transition from Visual Meteorological Conditions (VMC) to Instrument Meteorological Conditions (IMC), with continued flight into IMC, employing a fixed-based flight simulator. A total of three display concepts were employed for this evaluation. One display concept, referred to as the Attitude Indicator (AI) replicated instrumentation common in today's General Aviation (GA) aircraft. The second display concept, referred to as the Electronic Attitude Indicator (EAI), featured an enlarged attitude indicator that was more representative of a glass display that also included advanced flight symbology, such as a velocity vector. The third concept, referred to as the SVS display, was identical to the EAI except that computer-generated terrain imagery replaced the conventional blue-sky/brown-ground of the EAI. Pilot performance parameters, pilot control inputs and physiological data were recorded for post-test analysis. Situation awareness (SA) and qualitative pilot comments were obtained through questionnaires and free-form interviews administered immediately after the experimental session. Initial pilot performance data were obtained by instructor pilot observations. Physiological data (skin temperature, heart rate, and muscle flexure) were also recorded. Preliminary results indicate that far less errors were committed when using the EAI and SVS displays than when using conventional instruments. The specific data example examined in this report illustrates the benefit from SVS displays to avoid massive loss of SA conditions. All pilots acknowledged the enhanced situation awareness provided by the SVS display concept. Levels of

  14. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers.

    Science.gov (United States)

    Op den Dries, Sanna; Karimian, Negin; Westerkamp, Andrie C; Sutton, Michael E; Kuipers, Michiel; Wiersema-Buist, Janneke; Ottens, Petra J; Kuipers, Jeroen; Giepmans, Ben N; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J

    2016-07-01

    Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

  15. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

    Science.gov (United States)

    Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. β-Glucans (Saccharomyces cereviseae) Reduce Glucose Levels and Attenuate Alveolar Bone Loss in Diabetic Rats with Periodontal Disease

    Science.gov (United States)

    2015-01-01

    The objective of this study was to assess the effects of oral ingestion of β-glucans isolated from Saccharomyces cereviseae on the metabolic profile, expression of gingival inflammatory markers and amount of alveolar bone loss in diabetic rats with periodontal disease. Diabetes mellitus was induced in 48 Wistar rats by intraperitoneal injection of streptozotocin (80 mg/kg). After confirming the diabetes diagnosis, the animals were treated with β-glucans (by gavage) for 28 days. On the 14th day of this period, periodontal disease was induced using a ligature protocol. β-glucans reduced the amount of alveolar bone loss in animals with periodontal disease in both the diabetic and non-diabetic groups (p periodontal disease (p periodontal disease (p periodontal effects in diabetic rats with periodontal disease. PMID:26291983

  17. [Aging reduces contents of endogenous CO, cAMP and cGMP in rat penile tissues].

    Science.gov (United States)

    Qin, Wen-Bo; Wang, Shu-Qiu; Li, Ming; Kang, Yu-Ming; Gui, Shi-Liang; Chi, Bao-Jin

    2009-02-01

    To explore the relationship of aging with the changes of endogenous carbon monoxide (CO), cGMP and cAMP contents in the penile tissues of rats. Twenty-four male rats were equally divided into an 8-month, a 16-month and a 24-month group, and their penile erection was detected by injecting apomorphine, their penile cavernous body harvested, and the contents of CO, cAPM and cGMP detected by improved dual wavelength spectrophotometry. The contents of CO, cAPM and cGMP were reduced with the increase of age, with statistically significant differences between the three age groups (P < 0.01). Aging significantly decreased the contents of CO, cAMP and cGMP in the penile tissues of the rats, which suggests that aging might play an important role in erectile dysfunction.

  18. Localized Sympathectomy Reduces Mechanical Hypersensitivity by Restoring Normal Immune Homeostasis in Rat Models of Inflammatory Pain.

    Science.gov (United States)

    Xie, Wenrui; Chen, Sisi; Strong, Judith A; Li, Ai-Ling; Lewkowich, Ian P; Zhang, Jun-Ming

    2016-08-17

    Some forms of chronic pain are maintained or enhanced by activity in the sympathetic nervous system (SNS), but attempts to model this have yielded conflicting findings. The SNS has both pro- and anti-inflammatory effects on immunity, confounding the interpretation of experiments using global sympathectomy methods. We performed a "microsympathectomy" by cutting the ipsilateral gray rami where they entered the spinal nerves near the L4 and L5 DRG. This led to profound sustained reductions in pain behaviors induced by local DRG inflammation (a rat model of low back pain) and by a peripheral paw inflammation model. Effects of microsympathectomy were evident within one day, making it unlikely that blocking sympathetic sprouting in the local DRGs or hindpaw was the sole mechanism. Prior microsympathectomy greatly reduced hyperexcitability of sensory neurons induced by local DRG inflammation observed 4 d later. Microsympathectomy reduced local inflammation and macrophage density in the affected tissues (as indicated by paw swelling and histochemical staining). Cytokine profiling in locally inflamed DRG showed increases in pro-inflammatory Type 1 cytokines and decreases in the Type 2 cytokines present at baseline, changes that were mitigated by microsympathectomy. Microsympathectomy was also effective in reducing established pain behaviors in the local DRG inflammation model. We conclude that the effect of sympathetic fibers in the L4/L5 gray rami in these models is pro-inflammatory. This raises the possibility that therapeutic interventions targeting gray rami might be useful in some chronic inflammatory pain conditions. Sympathetic blockade is used for many pain conditions, but preclinical studies show both pro- and anti-nociceptive effects. The sympathetic nervous system also has both pro- and anti-inflammatory effects on immune tissues and cells. We examined effects of a very localized sympathectomy. By cutting the gray rami to the spinal nerves near the lumbar sensory

  19. Human SGT interacts with Bag-6/Bat-3/Scythe and cells with reduced levels of either protein display persistence of few misaligned chromosomes and mitotic arrest

    International Nuclear Information System (INIS)

    Winnefeld, Marc; Grewenig, Annabel; Schnoelzer, Martina; Spring, Herbert; Knoch, Tobias A.; Gan, Eugene C.; Rommelaere, Jean; Cziepluch, Celina

    2006-01-01

    The human small glutamine-rich TPR-containing protein (hSGT) is essential for cell division since RNA-interference-mediated strong reduction of hSGT protein levels causes mitotic arrest (M. Winnefeld, J. Rommelaere, and C. Cziepluch, The human small glutamine-rich TPR-containing protein is required for progress through cell division, Exp. Cell Res. 293 (2004), 43-57). Analysis of HeLa cells expressing a histone 2A-YFP fusion protein revealed the continuous presence of few mislocalized chromosomes close to the spindle poles as possible cause for hSGT depletion-dependent prometaphase arrest. Cells unable to rescue these mislocalized chromosomes into the metaphase plate died at this stage through apoptosis. In order to address hSGT function at the molecular level, mass spectrometry analysis of proteins which co-immunoprecipitated with Flag-tagged hSGT was performed. Thereby, Hsp70 and Bag-6/Bat-3/Scythe were identified as novel hSGT interaction partners while interaction with Hsc70 was confirmed. Results obtained with truncated versions of the hSGT protein revealed that Bag-6/Bat-3/Scythe and Hsp70 or Hsc70 were independently able to form complexes with hSGT. Interaction of hSGT with Hsc70, Hsp70 or Bag-6/Bat-3/Scythe was demonstrated in prometaphase, thereby suggesting a possible role for complexes containing hSGT and distinct (co)-chaperones during mitosis. Finally, cells from populations with reduced levels of Bag-6/Bat-3/Scythe also displayed persistence of mislocalized chromosomes and mitotic arrest, which strongly indicated that hSGT-Bag-6/Bat-3/Scythe complexes could be directly or indirectly required for complete chromosome congression

  20. A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats.

    Science.gov (United States)

    Allan, George; Lai, Muh-Tsann; Sbriscia, Tifanie; Linton, Olivia; Haynes-Johnson, Donna; Bhattacharjee, Sheela; Dodds, Robert; Fiordeliso, James; Lanter, James; Sui, Zhihua; Lundeen, Scott

    2007-01-01

    The pharmacological activity of JNJ-26146900 is described. JNJ-26146900 is a nonsteroidal androgen receptor (AR) ligand with tissue-selective activity in rats. The compound was evaluated in in vitro and in vivo models of AR activity. It binds to the rat AR with a K(i) of 400nM and acts as a pure androgen antagonist in an in vitro cell-based assay. Its in vitro profile is similar to the androgen antagonist bicalutamide (Casodex). In intact rats, JNJ-26146900 reduces ventral prostate weight with an oral potency (ED(50)) of 20-30mg/kg, again comparable to that of bicalutamide. JNJ-26146900 prevented prostate tumor growth in the Dunning rat model, maximally inhibiting growth at a dose of 10mg/kg. It slowed tumor growth significantly in a CWR22-LD1 mouse xenograft model of human prostate cancer. It was tested in aged male rats for its ability to prevent bone loss and loss of lean body mass following orchidectomy. After 6 weeks of dosing, bone volume decreased by 33% in orchidectomized versus intact vehicle-treated rats with a probability (P) of less than 0.05, as measured by micro-computerized tomography analysis. At a dose of 30mg/kg, JNJ-26146900 significantly reduced castration-induced tibial bone loss as indicated by the following parameters: bone volume, trabecular connectivity, trabecular number and spacing between trabeculae. Bone mineral density decreased from 229+/-34mg/cm(3) of hydroxyapatite to 166+/-26mg/cm(3) following orchidectomy, and was maintained at 194+/-20mg/cm(3) with JNJ-26146900 treatment (Pselective androgen receptor modulators (SARMs) have the potential for anabolic effects on bone and muscle while maintaining therapeutic efficacy in prostate cancer.

  1. Pristanic acid provokes lipid, protein, and DNA oxidative damage and reduces the antioxidant defenses in cerebellum of young rats.

    Science.gov (United States)

    Busanello, Estela Natacha Brandt; Lobato, Vannessa Gonçalves Araujo; Zanatta, Ângela; Borges, Clarissa Günther; Tonin, Anelise Miotti; Viegas, Carolina Maso; Manfredini, Vanusa; Ribeiro, César Augusto João; Vargas, Carmen Regla; de Souza, Diogo Onofre Gomes; Wajner, Moacir

    2014-12-01

    Zellweger syndrome (ZS) and some peroxisomal diseases are severe inherited disorders mainly characterized by neurological symptoms and cerebellum abnormalities, whose pathogenesis is poorly understood. Biochemically, these diseases are mainly characterized by accumulation of pristanic acid (Prist) and other fatty acids in the brain and other tissues. In this work, we evaluated the in vitro influence of Prist on redox homeostasis by measuring lipid, protein, and DNA damage, as well as the antioxidant defenses and the activities of aconitase and α-ketoglutarate dehydrogenase in cerebellum of 30-day-old rats. The effect of Prist on DNA damage was also evaluated in blood of these animals. Some parameters were also evaluated in cerebellum from neonatal rats and in cerebellum neuronal cultures. Prist significantly increased malondialdehyde (MDA) levels and carbonyl formation and reduced sulfhydryl content and glutathione (GSH) concentrations in cerebellum of young rats. It also caused DNA strand damage in cerebellum and induced a high micronuclei frequency in blood. On the other hand, this fatty acid significantly reduced α-ketoglutarate dehydrogenase and aconitase activities in rat cerebellum. We also verified that Prist-induced increase of MDA levels was totally prevented by melatonin and attenuated by α-tocopherol but not by the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester, indicating the involvement of reactive oxygen species in this effect. Cerebellum from neonate rats also showed marked alterations of redox homeostasis, including an increase of MDA levels and a decrease of sulfhydryl content and GSH concentrations elicited by Prist. Finally, Prist provoked an increase of dichlorofluorescein (DCFH) oxidation in cerebellum-cultivated neurons. Our present data indicate that Prist compromises redox homeostasis in rat cerebellum and blood and inhibits critical enzymes of the citric acid cycle that are susceptible to free radical attack. The

  2. (−-Epicatechin Reduces Blood Pressure and Improves Left Ventricular Function and Compliance in Deoxycorticosterone Acetate-Salt Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Douglas Jackson

    2018-06-01

    Full Text Available (−-Epicatechin (E is a flavanol found in green tea and cocoa and has been shown to attenuate tumour necrosis factor alpha (TNF-α-mediated inflammation, improve nitric oxide levels, promote endothelial nitric oxide synthase (eNOS activation and inhibit NADPH oxidase. This study investigated the effect of 28 days of low epicatechin dosing (1 mg/kg/day on the cardiovascular function of deoxycorticosterone acetate (DOCA-salt hypertensive rats. Wistar rats (n = 120, 8 weeks of age underwent uninephrectomy and were randomised into four groups (uninephrectomy (UNX, UNX + E, DOCA, DOCA + E. DOCA and DOCA + E rats received 1% NaCl drinking water along with subcutaneous injections of 25 mg deoxycorticosterone-acetate (in 0.4 mL of dimethylformamide every fourth day. UNX + E and DOCA + E rats received 1 mg/kg/day of epicatechin by oral gavage. Single-cell micro-electrode electrophysiology, Langendorff isolated-heart assessment and isolated aorta and mesenteric organ baths were used to assess cardiovascular parameters. Serum malondialdehyde concentration was used as a marker of oxidative stress. Myocardial stiffness was increased and left ventricular compliance significantly diminished in the DOCA control group, and these changes were attenuated by epicatechin treatment (p < 0.05. Additionally, the DOCA + E rats showed significantly reduced blood pressure and malondialdehyde concentrations; however, there was no improvement in left ventricular hypertrophy, electrophysiology or vascular function. This study demonstrates the ability of epicatechin to reduce blood pressure, prevent myocardial stiffening and preserve cardiac compliance in hypertrophied DOCA-salt rat hearts.

  3. Functional displays

    International Nuclear Information System (INIS)

    Angelis De, F.; Haentjens, J.

    1995-01-01

    The Functional Displays are directly derived from the Man-Machine Design key document: Function-Based Task Analysis. The presentation defines and describes the goals-means structure of the plant function along with applicable control volumes and parameters of interest. The purpose of the subject is to show, through an example of a preliminary design, what the main parts of a function are. (3 figs.)

  4. Display hardware

    International Nuclear Information System (INIS)

    Myers, D.R.

    1983-01-01

    To appreciate the limitations and possibilities of computer graphics it is necessary to have some acquaintance with the available technology. The aim of this chapter is to mention briefly the different display types and their 'ball-park' price ranges. It must be stressed that prices change rapidly, and so those quoted here are only intended to give an idea of the cost at the time of writing.

  5. Reduced connectivity and inter-hemispheric symmetry of the sensory system in a rat model of vulnerability to developing depression.

    Science.gov (United States)

    Ben-Shimol, E; Gass, N; Vollmayr, B; Sartorius, A; Goelman, G

    2015-12-03

    Defining the markers corresponding to a high risk of developing depression in humans would have major clinical significance; however, few studies have been conducted since they are not only complex but also require homogeneous groups. This study compared congenital learned helpless (cLH) rats, selectively bred for high stress sensitivity and learned helplessness (LH) behavior, to congenital non-learned helpless (cNLH) rats that were bred for resistance to uncontrollable stress. Naïve cLH rats show some depression-like behavior but full LH behavior need additional stress, making this model ideal for studying vulnerability to depression. Resting-state functional connectivity obtained from seed correlation analysis was calculated for multiple regions that were selected by anatomy AND by a data-driven approach, independently. Significance was determined by t-statistic AND by permutation analysis, independently. A significant reduction in functional connectivity was observed by both analyses in the cLH rats in the sensory, motor, cingulate, infralimbic, accumbens and the raphe nucleus. These reductions corresponded primarily to reduced inter-hemispheric connectivity. The main reduction however was in the sensory system. It is argued that reduced connectivity and inter-hemispheric connectivity of the sensory system reflects an internal convergence state which may precede other depressive symptomatology and therefore could be used as markers for vulnerability to the development of depression. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Ursodeoxycholic acid pretreatment reduces oral bioavailability of the multiple drug resistance-associated protein 2 substrate baicalin in rats.

    Science.gov (United States)

    Wu, Tao; Li, Xi-Ping; Xu, Yan-Jiao; Du, Guang; Liu, Dong

    2013-11-01

    Baicalin is a major bioactive component of Scutellaria baicalensis and a substrate of multiple drug resistance-associated protein 2. Expression of multiple drug resistance-associated protein 2 is regulated by NF-E2-related factor 2. The aim of this study was to explore whether ursodeoxycholic acid, an NF-E2-related factor 2 activator, could influence the oral bioavailability of baicalin. A single dose of baicalin (200 mg/kg) was given orally to rats pretreated with ursodeoxycholic acid (75 mg/kg and 150 mg/kg, per day, intragastrically) or normal saline (per day, intragastrically) for six consecutive days. The plasma concentration of baicalin was measured with the HPLC method. The result indicated that the oral bioavailability of baicalin was significantly and dose-dependently reduced in rats pretreated with ursodeoxycholic acid. Compared with control rats, the mean area under concentration-time curve of baicalin was reduced from 13.25 ± 0.24 mg/L h to 7.62 ± 0.15 mg/L h and 4.97 ± 0.21 mg/L h, and the C(max) value was decreased from 1.31 ± 0.03 mg/L to 0.62 ± 0.05 mg/L and 0.36 ± 0.04 mg/L in rats pretreated with ursodeoxycholic acid at doses of 75 mg/kg and 150 mg/kg, respectively, for six consecutive days. Hence, ursodeoxycholic acid treatment reduced the oral bioavailability of baicalin in rats, probably due to the enhanced efflux of baicalin from the intestine and liver by multiple drug resistance-associated protein 2. Georg Thieme Verlag KG Stuttgart · New York.

  7. Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90.

    Science.gov (United States)

    Li, Wanxia; Tao, Shaoyu; Wu, Qinghua; Wu, Tao; Tao, Ran; Fan, Jun

    2017-12-01

    Myocardial cell injury and cardiac myocyte apoptosis are associated with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury. The aim of this study was to explore the role of Gln on cardiac myocytes in a cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Following induction of sepsis in a CLP rat model, viral encoding heat shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8, and caspase-9 were detected by enzyme-linked immunosorbent assay. Rat cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90 overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2 expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly upregulated in the CLP model, which were reduced by Gln treatment and Hsp90 overexpression. Gln reduced apoptosis of cardiac myocytes in a rat model of sepsis, by promoting Hsp90 expression. Further studies are needed to determine the possible therapeutic action of Gln in sepsis in human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Ovarian hormone deprivation reduces oxytocin expression in Paraventricular Nucleus preautonomic neurons and correlates with baroreflex impairment in rats

    Directory of Open Access Journals (Sweden)

    Vitor Ulisses De Melo

    2016-10-01

    Full Text Available The prevalence of cardiovascular diseases including hypertension increases dramatically in women after menopause, however the mechanisms involved remain incompletely understood. Oxytocinergic (OTergic neurons are largely present within the paraventricular nucleus of the hypothalamus (PVN. Several studies have shown that OTergic drive from PVN to brainstem increases baroreflex sensitivity and improves autonomic control of the circulation. Since preautonomic PVN neurons express different types of estrogen receptors, we hypothesize that ovarian hormone deprivation causes baroreflex impairment, autonomic imbalance and hypertension by negatively impacting OTergic drive and oxytocin levels in pre-autonomic neurons. Here, we assessed oxytocin gene and protein expression (qPCR and immunohistochemistry within PVN subnuclei in sham-operated and ovariectomized Wistar rats. Conscious hemodynamic recordings were used to assess resting blood pressure and heart rate and the autonomic modulation of heart and vessels was estimated by power spectral analysis. We observed that the ovarian hormone deprivation in ovariectomized rats decreased baroreflex sensitivity, increased sympathetic and reduced vagal outflows to the heart and augmented the resting blood pressure. Of note, ovariectomized rats had reduced PVN oxytocin mRNA and protein expression in all pre-autonomic PVN subnuclei. Furthermore, reduced PVN oxytocin protein levels were positively correlated with decreased baroreflex sensitivity and negatively correlated with increased LF/HF ratio. These findings suggest that reduced oxytocin expression in OTergic neurons of the PVN contributes to the baroreflex dysfunction and autonomic dysregulation observed with ovarian hormone deprivation.

  9. ITI-signals and prelimbic cortex facilitate avoidance acquisition and reduce avoidance latencies, respectively, in male WKY rats

    Directory of Open Access Journals (Sweden)

    Kevin D Beck

    2014-11-01

    Full Text Available As a model of anxiety disorder vulnerability, male Wistar-Kyoto (WKY rats acquire lever-press avoidance behavior more readily than outbred Sprague Dawley rats, and their acquisition is enhanced by the presence of a discrete signal presented during the inter-trial intervals (ITIs, suggesting it is perceived as a safety signal. A series of experiments were conducted to determine if this is the case. Additional experiments investigated if the avoidance facilitation relies upon processing through medial prefrontal cortex (mPFC. The results suggest that the ITI-signal facilitates acquisition during the early stages of the avoidance acquisition process, when the rats are initially acquiring escape behavior and then transitioning to avoidance behavior. Post-avoidance introduction of the visual ITI-signal into other associative learning tasks failed to confirm that the visual stimulus had acquired the properties of a conditioned inhibitor. Shortening the signal from the entirety of the 3 min ITI to only the first 5 s of the 3 min ITI slowed acquisition during the first 4 sessions, suggesting the flashing light is not functioning as a feedback signal. The prelimbic (PL cortex showed greater activation during the period of training when the transition from escape responding to avoidance responding occurs. Only combined PL+infralimbic cortex lesions modestly slowed avoidance acquisition, but PL cortex lesions slowed avoidance response latencies. Thus, the flashing light ITI-signal is not likely perceived as a safety signal nor is it serving as a feedback signal. The functional role of the PL cortex appears to be to increase the drive towards responding to the threat of the warning signal. Hence, avoidance susceptibility displayed by male WKY rats may be driven, in part, both by external stimuli (ITI signal as well as by enhanced threat recognition to the warning signal via the PL cortex.

  10. Crocin reduced acrylamide-induced neurotoxicity in Wistar rat through inhibition of oxidative stress

    Directory of Open Access Journals (Sweden)

    Soghra Mehri

    2015-09-01

    Conclusion: The administration of crocin markedly improved behavioral and histopathological damages in Wistar rats exposed to ACR. Reduction of oxidative stress can be considered as an important mechanism of neuroprotective effects of crocin against ACR-induced toxicity.

  11. Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model

    Science.gov (United States)

    Xu, Meng; Xue, Wanli; Ma, Zhenhua; Bai, Jigang

    2016-01-01

    Purpose. To investigate the preventive effect of resveratrol (RES) on the formation of portal vein system thrombosis (PVST) in a rat fibrosis model. Methods. A total of 64 male SD rats, weighing 200–300 g, were divided into five groups: Sham operation, Splenectomy I, Splenectomy II, RES, and low molecular weight heparin (LMWH), with the former two groups as nonfibrosis controls. Blood samples were subjected to biochemical assays. Platelet apoptosis was measured by flow cytometry. All rats were euthanized for PVST detection one week after operation. Results. No PVST occurred in nonfibrosis controls. Compared to Splenectomy II, the incidences of PVST in RES and LMWH groups were significantly decreased (both p Splenectomy II (all p splenectomy in cirrhotic rat. Regulation of platelet function and induction of platelet apoptosis might be the underlying mechanisms. PMID:27433290

  12. The mechano-gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in decerebrate rats.

    Science.gov (United States)

    Copp, Steven W; Kim, Joyce S; Ruiz-Velasco, Victor; Kaufman, Marc P

    2016-02-01

    Mechanical and metabolic stimuli from contracting muscles evoke reflex increases in blood pressure, heart rate and sympathetic nerve activity. Little is known, however, about the nature of the mechano-gated channels on the thin fibre muscle afferents that contribute to evoke this reflex, termed the exercise pressor reflex. We determined the effect of GsMTx4, an inhibitor of mechano-gated Piezo channels, on the exercise pressor reflex evoked by intermittent contraction of the triceps surae muscles in decerebrated, unanaesthetized rats. GsMTx4 reduced the pressor, cardioaccelerator and renal sympathetic nerve responses to intermittent contraction but did not reduce the pressor responses to femoral arterial injection of compounds that stimulate the metabolically-sensitive thin fibre muscle afferents. Expression levels of Piezo2 channels were greater than Piezo1 channels in rat dorsal root ganglia. Our findings suggest that mechanically-sensitive Piezo proteins contribute to the generation of the mechanical component of the exercise pressor reflex in rats. Mechanical and metabolic stimuli within contracting skeletal muscles evoke reflex autonomic and cardiovascular adjustments. In cats and rats, gadolinium has been used to investigate the role played by the mechanical component of this reflex, termed the exercise pressor reflex. Gadolinium, however, has poor selectivity for mechano-gated channels and exerts multiple off-target effects. We tested the hypothesis that GsMTX4, a more selective mechano-gated channel inhibitor than gadolinium and a particularly potent inhibitor of mechano-gated Piezo channels, reduced the exercise pressor reflex in decerebrate rats. Injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the peak pressor (control: 24 ± 5, GsMTx4: 12 ± 5 mmHg, P acid. Moreover, injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the peak pressor (control: 24 ± 2, GsMTx4: 14 ± 3 mmHg, P reflex in

  13. Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum

    Directory of Open Access Journals (Sweden)

    Jeffrey Thomas Cole

    2012-04-01

    Full Text Available Brain cells expend large amounts of energy sequestering calcium (Ca2+, while loss of Ca2+ compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P, a parent substrate to several metabolic major pathways, including glycolysis. In several tissues, G6P alters the ability of the endoplasmic reticulum to sequester Ca2+. This led to the hypothesis that G6P regulates Ca2+ accumulation by acting as an endogenous ligand for sarco-endoplasmic reticulum calcium ATPase (SERCA. Whole brain ER microsomes were pooled from adult male Sprague-Dawley rats. Using radio-isotopic assays, 45Ca2+ accumulation was quantified following incubation with increasing amounts of G6P, in the presence or absence of thapsigargin, a potent SERCA inhibitor. To qualitatively assess SERCA activity, the simultaneous release of inorganic phosphate (Pi coupled with Ca2+ accumulation was quantified. Addition of G6P significantly and decreased Ca2+ accumulation in a dose-dependent fashion (1-10 mM. The reduction in Ca2+ accumulation was not significantly different that seen with addition of thapsigargin. Addition of glucose-1-phosphate or fructose-6-phosphate, or other glucose metabolic pathway intermediates, had no effect on Ca2+ accumulation. Further, the release of Pi was markedly decreased, indicating G6P-mediated SERCA inhibition as the responsible mechanism for reduced Ca2+ uptake. Simultaneous addition of thapsigargin and G6P did decrease inorganic phosphate in comparison to either treatment alone, which suggests that the two treatments have different mechanisms of action. Therefore, G6P may be a novel, endogenous regulator of SERCA activity. Additionally, pathological conditions observed during disease states that disrupt glucose homeostasis, may be attributable to Ca2+ dystasis caused by altered G6P regulation of SERCA activity

  14. Systemic N-terminal fragments of adrenocorticotropin reduce inflammation- and stress-induced anhedonia in rats.

    Science.gov (United States)

    Markov, Dmitrii D; Yatsenko, Ksenia A; Inozemtseva, Lyudmila S; Grivennikov, Igor A; Myasoedov, Nikolai F; Dolotov, Oleg V

    2017-08-01

    Emerging evidence implicates impaired self-regulation of the hypothalamic-pituitary-adrenal (HPA) axis and inflammation as important and closely related components of the pathophysiology of major depression. Antidepressants show anti-inflammatory effects and are suggested to enhance glucocorticoid feedback inhibition of the HPA axis. HPA axis activity is also negatively self-regulated by the adrenocorticotropic hormone (ACTH), a potent anti-inflammatory peptide activating five subtypes of melanocortin receptors (MCRs). There are indications that ACTH-mediated feedback can be activated by noncorticotropic N-terminal ACTH fragments such as a potent anti-inflammatory MC1/3/4/5R agonist α-melanocyte-stimulating hormone (α-MSH), corresponding to ACTH(1-13), and a MC3/5R agonist ACTH(4-10). We investigated whether intraperitoneal administration of rats with these peptides affects anhedonia, which is a core symptom of depression. Inflammation-related anhedonia was induced by a single intraperitoneal administration of a low dose (0.025mg/kg) of lipopolysaccharide (LPS). Stress-related anhedonia was induced by the chronic unpredictable stress (CUS) procedure. The sucrose preference test was used to detect anhedonia. We found that ACTH(4-10) pretreatment decreased LPS-induced increase in serum corticosterone and tumor necrosis factor (TNF)-α, and a MC3/4R antagonist SHU9119 blocked this effect. Both α-MSH and ACTH(4-10) alleviated LPS-induced anhedonia. In the CUS model, these peptides reduced anhedonia and normalized body weight gain. The data indicate that systemic α-MSH and ACTH(4-10) produce an antidepressant-like effect on anhedonia induced by stress or inflammation, the stimuli that trigger the release of ACTH and α-MSH into the bloodstream. The results suggest a counterbalancing role of circulating melanocortins in depression and point to a new approach for antidepressant treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Probiotic treatment reduces depressive-like behaviour in rats independently of diet.

    Science.gov (United States)

    Abildgaard, Anders; Elfving, Betina; Hokland, Marianne; Wegener, Gregers; Lund, Sten

    2017-05-01

    The gut microbiota has recently emerged as an important regulator of brain physiology and behaviour in animals, and ingestion of certain bacteria (probiotics) therefore appear to be a potential treatment for major depressive disorder (MDD). However, some conceptual and mechanistical aspects need further elucidation. We therefore aimed at investigating whether the habitual diet may interact with the effect of probiotics on depression-related behaviour and further examined some potentially involved mechanisms underlying the microbe-mediated behavioural effects. Forty male Sprague-Dawley rats were fed a control (CON) or high-fat diet (HFD) for ten weeks and treated with either a multi-species probiotic formulation or vehicle for the last five weeks. Independently of diet, probiotic treatment markedly reduced depressive-like behaviour in the forced swim test by 34% (95% CI: 22-44%). Furthermore, probiotic treatment skewed the cytokine production by stimulated blood mononuclear cells towards IFNγ, IL2 and IL4 at the expense of TNFα and IL6. In addition, probiotics lowered hippocampal transcript levels of factors involved in HPA axis regulation (Crh-r1, Crh-r2 and Mr), whereas HFD increased these levels. A non-targeted plasma metabolomics analysis revealed that probiotics raised the level of indole-3-propionic acid, a potential neuroprotective agent. Our findings clearly support probiotics as a potential treatment strategy in MDD. Importantly, the efficacy was not attenuated by intake of a "Western pattern" diet associated with MDD. Mechanistically, the HPA axis, immune system and microbial tryptophan metabolism could be important in this context. Importantly, our study lend inspiration to clinical trials on probiotics in depressed patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Vildagliptin reduces cardiac ischemic-reperfusion injury in obese orchiectomized rats.

    Science.gov (United States)

    Pongkan, Wanpitak; Pintana, Hiranya; Jaiwongkam, Thidarat; Kredphoo, Sasiwan; Sivasinprasasn, Sivaporn; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2016-10-01

    Obesity and testosterone deprivation are associated with coronary artery disease. Testosterone and vildagliptin (dipeptidyl peptidase-4 inhibitors) exert cardioprotection during ischemic-reperfusion (I/R) injury. However, the effect of these drugs on I/R heart in a testosterone-deprived, obese, insulin-resistant model is unclear. This study investigated the effects of testosterone and vildagliptin on cardiac function, arrhythmias and the infarct size in I/R heart of testosterone-deprived rats with obese insulin resistance. Orchiectomized (O) or sham operated (S) male Wistar rats were divided into 2 groups to receive normal diet (ND) or high-fat diet (HFD) for 12 weeks. Orchiectomized rats in each diet were divided to receive testosterone (2 mg/kg), vildagliptin (3 mg/kg) or the vehicle daily for 4 weeks. Then, I/R was performed by a 30-min left anterior descending coronary artery ligation, followed by a 120-min reperfusion. LV function, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. HFD groups developed insulin resistance at week 12. At week 16, cardiac function was impaired in NDO, HFO and HFS rats, but was restored in all testosterone- and vildagliptin-treated rats. During I/R injury, arrhythmia scores, infarct size and cardiac mitochondrial dysfunction were prominently increased in NDO, HFO and HFS rats, compared with those in NDS rats. Treatment with either testosterone or vildagliptin similarly attenuated these impairments during I/R injury. These finding suggest that both testosterone replacement and vildagliptin share similar efficacy for cardioprotection during I/R injury by decreasing the infarct size and attenuating cardiac mitochondrial dysfunction caused by I/R injury in testosterone-deprived rats with obese insulin resistance. © 2016 Society for Endocrinology.

  17. ACUTE HYPOGLYCEMIA RESULTS IN REDUCED CORTICAL NEURONAL INJURY IN THE DEVELOPING IUGR RAT

    OpenAIRE

    Maliszewski-Hall, Anne M.; Stein, Ariel B.; Alexander, Michelle; Ennis, Kathleen; Rao, Raghavendra

    2015-01-01

    Background Hypoglycemia (HG) is common in IUGR neonates. In normally grown (NG) neonatal rats, acute HG causes neuronal injury in the brain, cerebral cortex more vulnerable than the hippocampus (HPC). We hypothesized that the IUGR brain is less vulnerable to hypoglycemia-induced injury while preserving the regional variation in vulnerability. Methods We induced IUGR via bilateral uterine artery ligation on gestational day 19 (term 22d) rats. On postnatal day 14, insulin-induced HG of equivale...

  18. Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways.

    Science.gov (United States)

    Singh, Harpal; Kaur, Taranjeet; Manchanda, Shaffi; Kaur, Gurcharan

    2017-08-01

    Intermittent fasting-dietary restriction (IF-DR) is an increasingly popular intervention to promote healthy aging and delay age associated decline in brain functions. Also, the use of herbal interventions is gaining attention due to their non-pharmacological approach to treat several abnormalities and promote general health with least side effects. The present study was aimed to investigate the synergistic effects of IF-DR regimen with herbal supplementation on anxiety-like behavior and neuroinflammation in middle aged female rats. We used dried leaf powder of Withania somnifera and dried stem powder of Tinospora cordifolia for our study. The rats were divided into three groups: (1) Control group fed ad libitum (AL); (2) rats deprived of food for full day and fed ad libitum on every alternate day (IF-DR); and (3) IF-DR and herbal extract (DRH) group in which rats were fed ad libitum with herbal extract supplemented diet, every alternate day. Post regimen, the rats were tested for anxiety-like behavior and further used for study of key inflammatory molecules (NFκB, Iba1, TNFα, IL-1β, IL-6) and glial marker (GFAP) in hippocampus and piriform cortex regions of brain. The study was further extended to explore the effect of DRH regimen on stress response protein (HSP70) and calcium dependent regulators of synaptic plasticity (CaMKIIα, Calcineurin). Our data demonstrated that DRH regimen reduced anxiety-like behavior in middle age female rats and associated neuroinflammation by ameliorating key inflammatory cytokines and modulated stress response. The present data may provide scientific validation for anxiolytic and anti-inflammatory potential of herbal intervention combined with short term IF-DR regimen.

  19. S-nitrosoglutathione reduces tau hyper-phosphorylation and provides neuroprotection in rat model of chronic cerebral hypoperfusion.

    Science.gov (United States)

    Won, Je-Seong; Annamalai, Balasubramaniam; Choi, Seungho; Singh, Inderjit; Singh, Avtar K

    2015-10-22

    We have previously reported that treatment of rats subjected to permanent bilateral common carotid artery occlusion (pBCCAO), a model of chronic cerebral hypoperfusion (CCH), with S-nitrosoglutathione (GSNO), an endogenous nitric oxide carrier, improved cognitive functions and decreased amyloid-β accumulation in the brains. Since CCH has been implicated in tau hyperphosphorylation induced neurodegeneration, we investigated the role of GSNO in regulation of tau hyperphosphorylation in rat pBCCAO model. The rats subjected to pBCCAO had a significant increase in tau hyperphosphorylation with increased neuronal loss in hippocampal/cortical areas. GSNO treatment attenuated not only the tau hyperphosphorylation, but also the neurodegeneration in pBCCAO rat brains. The pBCCAO rat brains also showed increased activities of GSK-3β and Cdk5 (major tau kinases) and GSNO treatment significantly attenuated their activities. GSNO attenuated the increased calpain activities and calpain-mediated cleavage of p35 leading to production of p25 and aberrant Cdk5 activation. In in vitro studies using purified calpain protein, GSNO treatment inhibited calpain activities while 3-morpholinosydnonimine (a donor of peroxynitrite) treatment increased its activities, suggesting the opposing role of GSNO vs. peroxynitrite in regulation of calpain activities. In pBCCAO rat brains, GSNO treatment attenuated the expression of inducible nitric oxide synthase (iNOS) expression and also reduced the brain levels of nitro-tyrosine formation, thereby indicating the protective role of GSNO in iNOS/nitrosative-stress mediated calpain/tau pathologies under CCH conditions. Taken together with our previous report, these data support the therapeutic potential of GSNO, a biological NO carrier, as a neuro- and cognitive-protective agent under conditions of CCH. Published by Elsevier B.V.

  20. The broad-spectrum cation channel blocker pinokalant (LOE 908 MS) reduces brain infarct volume in rats

    DEFF Research Database (Denmark)

    Christensen, Thomas; Wienrich, Marion; Ensinger, Helmut A

    2005-01-01

    this period and the spontaneous temperature after course in control rats established in other experiments was imitated. Seven days later histological brain sections were prepared and the infarct volumes measured. Body temperature did not differ between the groups. Mean arterial blood pressure was slightly...... higher in the pinokalant group. Pinokalant treatment significantly reduced cortical infarct volume from 33.8+/-15.8 mm3 to 24.5+/-13.1 mm3 (control group versus pinokalant group, P=0.017, t-test). Taking the effective drug plasma concentration established in other experiments into account revealed...... and electrophysiologic status of the ischemic penumbra and to reduce lesion size on magnetic resonance images in the acute phase following middle cerebral artery occlusion in rats. The purpose of the present study was to investigate whether these beneficial effects of pinokalant are translated into permanent...

  1. Microlaser-based displays

    Science.gov (United States)

    Bergstedt, Robert; Fink, Charles G.; Flint, Graham W.; Hargis, David E.; Peppler, Philipp W.

    1997-07-01

    Laser Power Corporation has developed a new type of projection display, based upon microlaser technology and a novel scan architecture, which provides the foundation for bright, extremely high resolution images. A review of projection technologies is presented along with the limitations of each and the difficulties they experience in trying to generate high resolution imagery. The design of the microlaser based projector is discussed along with the advantage of this technology. High power red, green, and blue microlasers have been designed and developed specifically for use in projection displays. These sources, in combination with high resolution, high contrast modulator, produce a 24 bit color gamut, capable of supporting the full range of real world colors. The new scan architecture, which reduces the modulation rate and scan speeds required, is described. This scan architecture, along with the inherent brightness of the laser provides the fundamentals necessary to produce a 5120 by 4096 resolution display. The brightness and color uniformity of the display is excellent, allowing for tiling of the displays with far fewer artifacts than those in a traditionally tiled display. Applications for the display include simulators, command and control centers, and electronic cinema.

  2. Acetate supplementation reduces microglia activation and brain interleukin-1β levels in a rat model of Lyme neuroborreliosis

    Directory of Open Access Journals (Sweden)

    Brissette Catherine A

    2012-11-01

    Full Text Available Abstract Background We have found that acetate supplementation significantly reduces neuroglia activation and pro-inflammatory cytokine release in a rat model of neuroinflammation induced with lipopolysaccharide. To test if the anti-inflammatory effect of acetate supplementation is specific to a TLR4-mediated injury, we measured markers of neuroglia activation in rats subjected to B. burgdorferi-induced neuroborreliosis that is mediated in large part by a TLR2-type mechanism. Methods In this study, rats were subjected to Lyme neuroborreliosis following an intravenous infusion of B. burgdorferi (B31-MI-16. Acetate supplementation was induced using glyceryl triacetate (6g/kg by oral gavage. Immunohistochemistry, qPCR, and western blot analyses were used to measure bacterial invasion into the brain, neuroglial activation, and brain and circulating levels of interleukin 1β. Statistical analysis was performed using one-way analysis of variance (ANOVA followed by a Tukey’s post hoc tests or using a Student’s t test assuming unequal variances when appropriate. Results We found that acetate supplementation significantly reduced microglia activation by 2-fold as determined by immunohistochemical and western blot analysis. Further, acetate supplementation also reduced the expression of the pro-inflammatory cytokine IL-1β by 2-fold as compared to controls. On the other hand, the inoculation of rats with B. burgdorferi had no effect on astroglial activation as determined by immunocytochemistry and western blot analysis despite significant increases in circulation levels of antigen toward B. burgdorferi and presence of the bacteria in the central nervous system. Conclusions These results suggest that microglial activation is an essential component to neuroborreliosis and that acetate supplementation may be an effective treatment to reduce injury phenotype and possibly injury progression in Lyme neuroborreliosis.

  3. Rimonabant reduces the essential value of food in the genetically obese Zucker rat: an exponential demand analysis.

    Science.gov (United States)

    Rasmussen, Erin B; Reilly, William; Buckley, Jessica; Boomhower, Steven R

    2012-02-01

    Research on free-food intake suggests that cannabinoids are implicated in the regulation of feeding. Few studies, however, have characterized how environmental factors that affect food procurement interact with cannabinoid drugs that reduce food intake. Demand analysis provides a framework to understand how cannabinoid blockers, such as rimonabant, interact with effort in reducing demand for food. The present study examined the effects rimonabant had on demand for sucrose in obese Zucker rats when effort to obtain food varied and characterized the data using the exponential ("essential value") model of demand. Twenty-nine male (15 lean, 14 obese) Zucker rats lever-pressed under eight fixed ratio (FR) schedules of sucrose reinforcement, in which the number of lever-presses to gain access to a single sucrose pellet varied between 1 and 300. After behavior stabilized under each FR schedule, acute doses of rimonabant (1-10mg/kg) were administered prior to some sessions. The number of food reinforcers and responses in each condition was averaged and the exponential and linear demand equations were fit to the data. These demand equations quantify the value of a reinforcer by its sensitivity to price (FR) increases. Under vehicle conditions, obese Zucker rats consumed more sucrose pellets than leans at smaller fixed ratios; however, they were equally sensitive to price increases with both models of demand. Rimonabant dose-dependently reduced reinforcers and responses for lean and obese rats across all FR schedules. Data from the exponential analysis suggest that rimonabant dose-dependently increased elasticity, i.e., reduced the essential value of sucrose, a finding that is consistent with graphical depictions of normalized demand curves. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Piper sarmentosum is comparable to glycyrrhizic acid in reducing visceral fat deposition in adrenalectomised rats given dexamethasone.

    Science.gov (United States)

    Fairus, A; Ima Nirwana, S; Elvy Suhana, M R; Tan, M H; Santhana, R; Farihah, H S

    2013-01-01

    Visceral obesity may be due to the dysregulation of cortisol production or metabolism that lead to metabolic disease. In adipose tissue, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 regulates cortisol metabolism (11beta-HSD1). A previous study showed an increase in the visceral fat deposition in adrenalectomised rats given intramuscular dexamethasone. Glycyrrhizic acid (GCA) has been shown to reduce fat deposition because it is a known potent inhibitor of the 11beta-HSD1 enzyme. Piper sarmentosum (PS) is an edible medicinal plant commonly used in Asia as traditional medicine for treating diabetes, hypertension and joint pains. In this study, we determined the effects of PS extract on the disposition and morphology of perirenal adipocytes of adrenalectomised rats given intramuscular dexamethasone. A total of 21 male Spraque Dawley rats were adrenalectomised and given intramuscular dexamethasone, 120 μg/kg/day. These rats were further divided into three groups: adrenalectomised control (ADR+Dexa; n=7), GCA-treated (ADR+Dexa+GCA; dose=240 mg/kg/day; n=7) and PS-treated (ADR+Dexa+PS; dose=125 mg/kg/day; n=7) groups. The various treatments were given via gastric gavage following 2 weeks of adrenalectomy. Treatment with PS extract for 8 weeks showed decreased deposition of perirenal adipocytes which was similar to the GCA-treated group. However, PS-treated rats had thinner adipocyte membrane compared with that of the GCA-treated group. In conclusion, PS extract decreased perirenal fat deposition and reduced the diameter of the adipocyte membrane. However, the mechanisms of action needed further study.

  5. Repeated rat-forced swim test: reducing the number of animals to evaluate gradual effects of antidepressants.

    Science.gov (United States)

    Mezadri, T J; Batista, G M; Portes, A C; Marino-Neto, J; Lino-de-Oliveira, C

    2011-02-15

    The forced swim test (FST) is a pre-clinical test to short and long term treatment with antidepressant drugs (ADT), which requires between-subject designs. Herein a modified protocol of the FST using within-subject design (repeated rat-FST) was evaluated. Male Wistar rats were submitted to 15 min of swimming (Day 1: pretest) followed by three subsequent 5 min-swimming tests one week apart (Day 2: test, Day 7: retest 1, Day 14: retest 2). To determine the temporal and factorial characteristics of the variables scored in the repeated rat-FST, the protocol was carried out in untreated animals (E1). To validate the method, daily injections of Fluoxetine (FLX, 2.5mg/kg, i.p.) or saline were given over a 2-week period (E2). Tests and retests have been videotaped for further register of the latency, frequency and duration of behaviors. Over retesting the latency to immobility decreased whereas duration of immobility tended to increase. Factorial analysis revealed that the test, the retest 1 as well as the retest 2 have variables suitable to detection of antidepressant-like effects of ADT. Compared to saline, FLX chronically administrated reduced duration of immobility whereas increased duration of swimming in retest 2. The data suggest that repeated rat-FST detected the gradual increase in the efficacy of low doses of FLX over time. Therefore, repeated rat-FST seemed suitable to detect short and long term effects of selective serotonin reuptake inhibitors, or other ADT, thus reducing the number of animals used in the screenings of this type of compounds. © 2010 Elsevier B.V. All rights reserved.

  6. Mild Contralesional Hypothermia Reduces Use of the Unimpaired Forelimb in a Skilled Reaching Task After Motor Cortex Injury in Rats.

    Science.gov (United States)

    Klahr, Ana C; Fagan, Kelly; Aziz, Jasmine R; John, Roseleen; Colbourne, Frederick

    2018-06-01

    Therapeutic hypothermia (TH) mitigates neuronal injury in models of ischemic stroke. Although this therapy is meant for injured tissue, most protocols cool the whole body, including the contralesional hemisphere. Neuroplasticity responses within this hemisphere can affect functional outcome. Thus, cooling the contralesional hemisphere serves no clear neuroprotective function and may instead be detrimental. In this study, we cooled the contralesional hemisphere to determine whether this harms behavioral recovery after cortical injury in rats. All rats were trained on skilled reaching and walking tasks. Rats then received a motor cortex insult contralateral to their dominant paw after which they were randomly assigned to focal contralesional TH (∼33°C) for 1-48, 1-97, or 48-96 hours postinjury, or to a normothermic control group. Contralesional cooling did not impact lesion volume (p = 0.371) and had minimal impact on neurological outcome of the impaired limb. However, rats cooled early were significantly less likely to shift paw preference to the unimpaired paw (p ≤ 0.043), suggesting that cooling reduced learned nonuse. In a second experiment, we tested whether cooling impaired learning of the skilled reaching task in naive rats. Localized TH applied to the hemisphere contralateral or ipsilateral to the preferred paw did not impair learning (p ≥ 0.677) or dendritic branching/length in the motor cortex (p ≥ 0.105). In conclusion, localized TH did not impair learning or plasticity in the absence of neural injury, but contralesional TH may reduce unwanted shifts in limb preference after stroke.

  7. Dietary D-psicose reduced visceral fat mass in high-fat diet-induced obese rats.

    Science.gov (United States)

    Chung, Young-Mee; Hyun Lee, Joo; Youl Kim, Deuk; Hwang, Se-Hee; Hong, Young-Ho; Kim, Seong-Bo; Jin Lee, Song; Hye Park, Chi

    2012-02-01

    D-Psicose, a C-3 epimer of D-fructose, has shown promise in reducing body fat accumulation in normal rats and plasma glucose level in genetic diabetic mice. Effects of D-psicose on diet-induced obesity are not clearly elucidated, and we investigated food intake, body weight, and fat accumulation in rats fed high-fat (HF) diet. Sprague-Dawley rats became obese by feeding HF diet for 4 wk, and were assigned either to normal or HF diet supplemented with or without D-psicose, sucrose, or erythritol for 8 wk. Changing HF to normal diet gained less body weight and adipose tissue due to different energy intake. D-psicose-fed rats exhibited lower weight gain, food efficiency ratio, and fat accumulation than erythritol- and sucrose-fed rats. This effect was more prominent in D-psicose-fed rats with normal diet than with HF diet, suggesting combination of psicose and calorie restriction further reduced obesity. There was no difference in serum cholesterol/high-density lipoprotein (HDL)-C and low-density lipoprotein (LDL)-C/HDL-C ratios between D-psicose group and other groups. Liver weight in 5% psicose group with normal diet was higher than in other groups, but histopathological examination did not reveal any psicose-related change. D-Psicose inhibited the differentiation of mesenchymal stem cell (MSC) to adipose tissue in a concentration-dependent manner. These results demonstrate that D-psicose produces a marked decrease, greater than erythritol, in weight gain and visceral fat in an established obesity model by inhibiting MSC differentiation to adipocyte. Thus, D-psicose can be useful in preventing and reducing obesity as a sugar substitute and food ingredient. We can develop D-psicose as a sugar substitute and food ingredient since it can prevent obesity in normal people, but also suppress adiposity as a sugar substitute or food ingredients with antiobesity effect in obese people. D-psicose can be unique functional sweetener because of its function of reducing visceral

  8. Involvement of aberrant DNA methylation on reduced expression of lysophosphatidic acid receptor-1 gene in rat tumor cell lines

    International Nuclear Information System (INIS)

    Tsujiuchi, Toshifumi; Shimizu, Kyoko; Onishi, Mariko; Sugata, Eriko; Fujii, Hiromasa; Mori, Toshio; Honoki, Kanya; Fukushima, Nobuyuki

    2006-01-01

    Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell proliferation, migration, and protects cells from apoptosis. It interacts with specific G protein-coupled transmembrane receptors. Recently, it has been reported that alterations of LPA receptor expression might be important in the malignant transformation of tumor cells. Therefore, to assess an involvement of DNA methylation in reduced expression of the LPA receptor-1 (lpa1) gene, we investigated the expression of the lpa1 gene and its DNA methylation patterns in rat tumor cell lines. Both rat brain-derived neuroblastoma B103 and liver-derived hepatoma RH7777 cells used in this study indicated no expression of lpa1. For the analysis of methylation status, bisulfite sequencing was performed with B103 and RH7777 cells, comparing with other lpa1 expressed cells and normal tissues of brain and liver. The lpa1 expressed cells and tissues were all unmethylated in this region of lpa1. In contrast, both B103 and RH7777 cells were highly methylated, correlating with reduced expression of the lpa1. Treatment with 5-aza 2'-deoxycytidine induced expression of lpa1 gene in B103 and RH7777 cells after 24 h. In RH7777 cells treated with 5-aza 2'-deoxycytidine, stress fiber formation was also observed in response to LPA in RH7777 cells, but not in untreated RH7777 cells. These results suggest that aberrant DNA methylation of the lpa1 gene may be involved in its reduced expression in rat tumor cells

  9. Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats.

    Science.gov (United States)

    Guerrero, Estela; Voces, Felipe; Ardanaz, Noelia; Montero, María José; Arévalo, Miguel; Sevilla, María Angeles

    2003-09-01

    The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.

  10. Pre-existing liver cirrhosis reduced the toxic effect of diethylene glycol in a rat model due to the impaired hepatic alcohol dehydrogenase.

    Science.gov (United States)

    Ming Xing Huang; Xiao Mou Peng; Lin Gu; Gui Hua Chen

    2011-09-01

    Hepatic metabolizing enzymes of diethylene glycol (DEG) are impaired in liver diseases. Thus, the purpose of this study was to increase our understandings in metabolism and toxicology of DEG by clarifying the influences of pre-existing liver disease. Forty Sprague-Dawley rats with carbon tetrachloride-induced liver cirrhosis and 20 control rats were intraperitoneally administered a single dose of DEG, and randomly killed 1, 2, 5 or 8 days following exposure. Compared with control rats, the model rats had significantly higher blood CO(2)-combining power, lower blood urine nitrogen, serum creatinine and alanine aminotransferase levels on the second day and a lower mortality rate on the eighth day following DEG exposure. Enlargements of liver and kidneys and degeneration and necrosis of hepatocytes and renal tubules in the model rats was also less serious than in the control rats. Urine DEG levels were significantly higher on the first day in the model rats than the control rats (46.65 ± 8.79 mg vs 18.88 ± 6.18 mg, p activity in the model rats was significantly lower than that in the control rats, which was positively related to renal damage. The toxic effects of DEG in rats with pre-existing liver cirrhosis are significantly reduced, which may be due to the decreased hepatic ADH activity. It suggests that the metabolite of ADH is responsible for DEG poisoning, and this toxic metabolite may mainly originate in the liver.

  11. Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

    Directory of Open Access Journals (Sweden)

    Przemysław Rzodkiewicz

    2016-10-01

    Full Text Available Objectives : Esculetin (6,7-dihydroxycoumarin is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9. Because both inhibition of lipoxygenases and inhibition of matrix metalloproteinases are effective strategies in the treatment of rheumatoid arthritis, we investigated whether esculetin may be effective in adjuvant-induced arthritis in rats. Material and methods : The study was performed on male Lewis rats, in the adjuvant-induced arthritis model. Rats were divided into two groups: control (treated with 1% methylcellulose and experimental (treated with esculetin – 10 mg/kg ip.. The tested compound was administered for 5 consecutive days starting on the 21st day after induction of arthritis. Each group consisted of 7 animals. After 5 days of treatment, rats were anesthetized. The concentration of leukotriene B4 (LTB4 in plasma was determined by a competitive enzyme immunoassay. Results : The LTB4 level in plasma of rats with adjuvant-induced arthritis is increased in comparison to rats without inflammation (362 ±34 vs. 274 ±15 pg/ml, p < 0.01, respectively. Five-day treatment with esculetin in adjuvant-induced arthritis rats decreases the LTB4 level to a level comparable with rats without inflammation (284 ±23 pg/ml, p < 0.01. Conclusions : LTB4 is the most potent chemotactic agent influencing neutrophil migration into the joint. It is known that its level in serum of patients with active rheumatoid arthritis is increased and correlates with disease severity. Some other lipoxygenase inhibitors have already been tested as potential drug candidates in clinical and preclinical trials for rheumatoid arthritis (Zileuton, PF-4191834. Because esculetin decreases the LTB4 level in plasma of rats in adjuvant-induced arthritis, it may also be considered as an attractive

  12. Branched-Chain Amino Acid Supplementation Reduces Oxidative Stress and Prolongs Survival in Rats with Advanced Liver Cirrhosis

    Science.gov (United States)

    Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C.; Takei, Yoshiyuki

    2013-01-01

    Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (PBCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183

  13. Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Motoh Iwasa

    Full Text Available Long-term supplementation with branched-chain amino acids (BCAA is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05. The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.

  14. Study of the Effects on Student Knowledge and Perceptions of Activities Related to Submetering the 6th Grade Wing of a Middle School, to Displaying the Carbon Footprint, and to Efforts to Reduce Energy Consumption and Greenhouse Gases

    Science.gov (United States)

    Peck, Rick

    2009-01-01

    The purpose of the study was to determine the effects upon student knowledge and perceptions regarding greenhouse gas emissions as a result of an intervention relying upon the submetering the 6th grade wing of a Middle School, displaying the information regarding electrical consumption and carbon footprint, and reducing the electrical consumption…

  15. Reduced expression of Nogo-A leads to motivational deficits in rats

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    Thomas eEnkel

    2014-01-01

    Full Text Available Nogo-A is an important neurite growth-regulatory protein in the adult and developing nervous system. Mice lacking Nogo-A, or rats with neuronal Nogo-A deficiency, exhibit behavioral abnormalities such as impaired short-term memory, decreased prepulse inhibition and behavioral inflexibility. In the current study we extended the behavioral profile of the Nogo-A deficient rat line with respect to reward sensitivity and motivation and determined the concentrations of the monoamines dopamine and serotonin in the prefrontal cortex, dorsal striatum and nucleus accumbens. Using a limited access consumption task, we found similar intake of a sweet condensed milk solution following ad libitum or restricted feeding in wild-type and Nogo-A deficient rats, indicating normal reward sensitivity and translation of hunger into feeding behavior. When tested for motivation in a spontaneous progressive ratio task, Nogo-A rats exhibited lower break points and tended to have lower ‘highest completed ratios’. Further, under extinction conditions responding ceased substantially earlier in these rats. Finally, in the prefrontal cortex we found increased tissue levels of serotonin, while dopamine was unaltered. Dopamine and serotonin levels were also unaltered in the dorsal striatum and the nucleus accumbens. In summary, these results suggest a role for Nogo-A regulated processes in motivated behavior and related neurochemistry. The behavioral pattern observed resembles aspects of the negative symptomatology of schizophrenia.

  16. Electroacupuncture reduces the evoked responses of the spinal dorsal horn neurons in ankle-sprained rats

    Science.gov (United States)

    Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon

    2011-01-01

    Acupuncture is shown to be effective in producing analgesia in ankle sprain pain in humans and animals. To examine the underlying mechanisms of the acupuncture-induced analgesia, the effects of electroacupuncture (EA) on weight-bearing forces (WBR) of the affected foot and dorsal horn neuron activities were examined in a rat model of ankle sprain. Ankle sprain was induced manually by overextending ligaments of the left ankle in the rat. Dorsal horn neuron responses to ankle movements or compression were recorded from the lumbar spinal cord using an in vivo extracellular single unit recording setup 1 day after ankle sprain. EA was applied to the SI-6 acupoint on the right forelimb (contralateral to the sprained ankle) by trains of electrical pulses (10 Hz, 1-ms pulse width, 2-mA intensity) for 30 min. After EA, WBR of the sprained foot significantly recovered and dorsal horn neuron activities were significantly suppressed in ankle-sprained rats. However, EA produced no effect in normal rats. The inhibitory effect of EA on hyperactivities of dorsal horn neurons of ankle-sprained rats was blocked by the α-adrenoceptor antagonist phentolamine (5 mg/kg ip) but not by the opioid receptor antagonist naltrexone (10 mg/kg ip). These data suggest that EA-induced analgesia in ankle sprain pain is mediated mainly by suppressing dorsal horn neuron activities through α-adrenergic descending inhibitory systems at the spinal level. PMID:21389301

  17. Antibiotic suppression of intestinal microbiota reduces heme-induced lipoperoxidation associated with colon carcinogenesis in rats.

    Science.gov (United States)

    Martin, O C B; Lin, C; Naud, N; Tache, S; Raymond-Letron, I; Corpet, D E; Pierre, F H

    2015-01-01

    Epidemiological studies show that heme iron from red meat is associated with increased colorectal cancer risk. In carcinogen-induced-rats, a heme iron-rich diet increases the number of precancerous lesions and raises associated fecal biomarkers. Heme-induced lipoperoxidation measured by fecal thiobarbituric acid reagents (TBARs) could explain the promotion of colon carcinogenesis by heme. Using a factorial design we studied if microbiota could be involved in heme-induced carcinogenesis, by modulating peroxidation. Rats treated or not with an antibiotic cocktail were given a control or a hemoglobin-diet. Fecal bacteria were counted on agar and TBARs concentration assayed in fecal water. The suppression of microbiota by antibiotics was associated with a reduction of crypt height and proliferation and with a cecum enlargement, which are characteristics of germ-free rats. Rats given hemoglobin diets had increased fecal TBARs, which were suppressed by the antibiotic treatment. A duplicate experiment in rats given dietary hemin yielded similar results. These data show that the intestinal microbiota is involved in enhancement of lipoperoxidation by heme iron. We thus suggest that microbiota could play a role in the heme-induced promotion of colorectal carcinogenesis.

  18. Curcumin accelerates the repair of sciatic nerve injury in rats through reducing Schwann cells apoptosis and promoting myelinization.

    Science.gov (United States)

    Zhao, Zhiwei; Li, Xiaoling; Li, Qing

    2017-08-01

    Schwann cells (SCs) play an indispensable role in the repair and regeneration of injured peripheral nerve. Curcumin can reduce SCs apoptosis, and promote the regeneration and functional recovery of injured peripheral nerves. However, the corresponding mechanisms are not clear. The article was aimed to explore the effect and corresponding mechanisms of curcumin on the repair of sciatic nerve injury in rats. After surgery induced sciatic nerve injury, the model rats were divided into three groups and treated with curcumin, curcumin+PD98059 and curcumin+IGF-1 respectively for 4days. The phosphorylation of Erk1/2 and Akt, and the expression of LC3-II, Beclin 1 and p62 were measured using western blotting. After treatment for 60days, myelination of the injured sciatic nerve was evaluated by MBP immunohistochemical staining and the expression of PMP22, Fibrin and S100 were determined using qRT-PCR and western blotting. In vitro, RSC96 cells were starved for 12h to induce autophagy, and received DMSO, curcumin, PD98059+curcumin, IGF-1+curcumin and BFA1 respectively. The phosphorylation of Erk1/2、Akt and the expression of LC3-II, Beclin 1, p62, PMP22, Fibrin and S100 were measured using western blotting, and the cell apoptosis was detected by flow cytometry. Curcumin could promote injury-induced cell autophagy, remyelination and axon regeneration in sciatic nerve of rats. In vitro, curcumin could accelerate cell autophagy through regulating autophagy related Erk1/2 and Akt pathway, prevent cell apoptosis and promote expression of PMP22 and S100, and reduced deposition of Fibrin in cultured RSC96 SCs. Curcumin could accelerate injured sciatic nerve repair in rats through reducing SCs apoptosis and promoting myelinization. Copyright © 2017. Published by Elsevier Masson SAS.

  19. Acute stress worsens the deficits in appetitive behaviors for social and sexual stimuli displayed by rats after long-term withdrawal from morphine.

    Science.gov (United States)

    Bai, Yunjing; Belin, David; Zheng, Xigeng; Liu, Zhengkui; Zhang, Yue

    2017-06-01

    Negative affective states, e.g., anhedonia, are suggested to be involved in the long-lasting motivational processes associated with relapse. Here, we investigated whether anhedonic behaviors could be elicited by an acute stress after protracted abstinence from morphine. The behavioral responses to natural stimuli following exposure to an acute stress were examined after 14 days of withdrawal from morphine. Male rats were pretreated with either a binge-like morphine regimen or daily saline injections for 5 days. The motivation for two natural stimuli, i.e., a social stimulus (male rat) and a sexual stimulus (estrous female rat), was measured, following exposure to an acute stress (intermittent foot shock, 0.5 mA * 0.5 s * 10 min; mean inter-shock interval 40 s), under three conditions: free approach and effort- and conflict-based approaches. Foot-shock-induced stress did not influence free-approach behavior (sniffing time) towards the social or sexual stimulus. However, in the effort-based approach task, the stressed morphine-withdrawn rats demonstrated an attenuated motivation to climb over a partition to approach the social stimulus while the stressed saline-pretreated rats showed an increased motivation to approach the social stimulus. When an aversive stimulus (pins) was introduced in order to induce an approach-avoidance conflict, both drug-withdrawn and drug-naïve groups exhibited a bimodal distribution of approach behavior towards the sexual stimulus after the stress was introduced, i.e., the majority of rats had low risky appetitive behaviors but a minority of them showed rather highly "risky" approach behavior. The acute stress induces differential motivational deficits for social and sexual rewards in protracted drug-abstinent rats.

  20. Kefir administration reduced progression of renal injury in STZ-diabetic rats by lowering oxidative stress.

    Science.gov (United States)

    Punaro, Giovana R; Maciel, Fabiane R; Rodrigues, Adelson M; Rogero, Marcelo M; Bogsan, Cristina S B; Oliveira, Marice N; Ihara, Silvia S M; Araujo, Sergio R R; Sanches, Talita R C; Andrade, Lucia C; Higa, Elisa M S

    2014-02-15

    This study aimed at assessing the effects of Kefir, a probiotic fermented milk, on oxidative stress in diabetic animals. The induction of diabetes was achieved in adult male Wistar rats using streptozotocin (STZ). The animals were distributed into four groups as follows: control (CTL); control Kefir (CTLK); diabetic (DM) and diabetic Kefir (DMK). Starting on the 5th day of diabetes, Kefir was administered by daily gavage at a dose of 1.8 mL/day for 8 weeks. Before and after Kefir treatment, the rats were placed in individual metabolic cages to obtain blood and urine samples to evaluate urea, creatinine, proteinuria, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and C-reactive protein (CRP). After sacrificing the animals, the renal cortex was removed for histology, oxidative stress and NOS evaluation. When compared to CTL rats, DM rats showed increased levels of glycemia, plasmatic urea, proteinuria, renal NO, superoxide anion, TBARS, and plasmatic CRP; also demonstrated a reduction in urinary urea, creatinine, and NO. However, DMK rats showed a significant improvement in most of these parameters. Despite the lack of differences observed in the expression of endothelial NO synthase (eNOS), the expression of inducible NO synthase (iNOS) was significantly lower in the DMK group when compared to DM rats, as assessed by Western blot analysis. Moreover, the DMK group presented a significant reduction of glycogen accumulation within the renal tubules when compared to the DM group. These results indicate that Kefir treatment may contribute to better control of glycemia and oxidative stress, which is associated with the amelioration of renal function, suggesting its use as a non-pharmacological adjuvant to delay the progression of diabetic complications. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Reduced efficacy of fluoxetine following MDMA ("Ecstasy")-induced serotonin loss in rats.

    Science.gov (United States)

    Durkin, Sarah; Prendergast, Alison; Harkin, Andrew

    2008-12-12

    Long-term serotonin (5-HT) neuronal loss is currently a major cause of concern associated with recreational use of the substituted amphetamine 3,4 methylenedioxymethamphetamine (MDMA; "Ecstasy"). Such loss may be problematic considering that psychiatric disorders such as depression and anxiety and responses to first line treatments for these disorders are associated with 5-HT. In this study the effects of prior exposure to MDMA on behavioural and central neurochemical changes induced by the serotonin (5-HT) re-uptake inhibitor and antidepressant fluoxetine were examined in rats. Animals were administered MDMA (10 mg/kg. i.p.) four times daily for two consecutive days. One week later the animals were subjected to treatment with fluoxetine (10 mg/kg, i.p.). Fluoxetine treatment groups received either acute (saline injections for 20 days followed by 3 fluoxetine treatments over 24 h) or chronic (once daily fluoxetine for 21 days) drug administration. Prior exposure to MDMA resulted in an attenuation of fluoxetine-induced swimming behaviour in the modified forced swimming test (FST); a behavioural test of antidepressant action. In parallel MDMA treatment resulted in significant regional depletions of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) accompanied by a reduction in cortical [3H] paroxetine binding to nerve terminal 5-HT transporters. MDMA-induced 5-HT loss was enhanced in animals following chronic fluoxetine administration. Elimination of fluoxetine and its metabolite norfluoxetine from the brain abolished this interaction between MDMA and fluoxetine treatment. Fluoxetine administration reduced both 5-HIAA and the 5-HIAA:5-HT metabolism ratio, which was attenuated in animals pre-treated with MDMA. Overall the results show that MDMA induces long-term 5-HT loss in the rodent brain and consequently diminishes behaviour and reductions in 5-HT metabolism induced by the antidepressant fluoxetine. These results have potential clinical relevance

  2. Role of thirst and visual barriers in the differential behavior displayed by streptozotocin-treated rats in the elevated plus-maze and the open field test.

    Science.gov (United States)

    Rebolledo-Solleiro, Daniela; Crespo-Ramírez, Minerva; Roldán-Roldán, Gabriel; Hiriart, Marcia; Pérez de la Mora, Miguel

    2013-08-15

    Conflicting results have been obtained by several groups when studying the effects of streptozotocin (STZ)-treated rats in the elevated plus-maze (EPM). Since thirst is a prominent feature in STZ-induced diabetic-like condition, we studied whether the walls of the closed arms of the EPM, by limiting the search for water in the environment, may contribute to the observed differential behavioral outcomes. The aim of this study was to ascertain whether visual barriers within the EPM have an influence on the behavior of STZ-treated rats in this test of anxiety. A striking similarity between STZ-treated (50 mg/kg, i.p., in two consecutive days) and water deprived rats (72 h) was found in exploratory behavior in the EPM, showing an anxiolytic-like profile. However the anxiolytic response of STZ-treated rats exposed to the EPM shifts into an anxiogenic profile when they are subsequently tested in the open-field test, which unlike the EPM is devoid of visual barriers. Likewise, water deprived rats (72 h) also showed an anxiogenic profile when they were exposed to the open-field test. Our results indicate that experimental outcomes based on EPM observations can be misleading when studying physiological or pathological conditions, e.g. diabetes, in which thirst may increase exploratory behavior. © 2013.

  3. Aloe vera extract reduces 8-oxo-2'-deoxyguanosine levels and improves total antioxidants in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Wulan Christijanti

    2017-04-01

    Full Text Available Background Diabetes mellitus is a chronic disease caused by lack of insulin production in the pancreas or by insulin resistance, the disease being characterized by elevated blood glucose levels. Hyperglycemia in diabetes could lead to oxidative stress due to the rise in 8-oxo-2'-deoxyguanosine (8-oxo-dG levels and the decrease in levels of total antioxidant status (TAS. The purpose of this study was to assess the effect Aloe vera extract on 8-oxo-dG level and total antioxidant status in diabetic rat testis.   Methods This was an experimental laboratory study with 20 rat samples which were divided into 4 groups (1 control group and 3 treatment groups. Diabetes was induced in the rats by streptozotocin (STZ at 65 mg/kgBW. The diabetic rats were then treated for 28 days with Aloe vera extract at 0 mg (P0, 200 mg rind (P1, 200 mg pulp (P2, respectively. The level of 8 -oxo-dG was measured by ELISA and total antioxidant status with 2,2' -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS. Data were analyzed with ANOVA and Least Significant Difference Advanced Test at P<0.05.   Results 8-Oxo-dG levels were significantly different between the control group and both P0 and P2, but not between the control group and P1. Among the treatment groups the 8-oxo-dG levels were significantly different. Mean total antioxidant status was significantly different between control and treatment groups, and also between treatment groups (p<0.05.   Conclusions Aloe vera extract reduced free radicals (level of 8-oxo-dG and increased the total antioxidant status in diabetic rat testis.

  4. Behavioral tolerance to lysergic acid diethylamide is associated with reduced serotonin-2A receptor signaling in rat cortex.

    Science.gov (United States)

    Gresch, Paul J; Smith, Randy L; Barrett, Robert J; Sanders-Bush, Elaine

    2005-09-01

    Tolerance is defined as a decrease in responsiveness to a drug after repeated administration. Tolerance to the behavioral effects of hallucinogens occurs in humans and animals. In this study, we used drug discrimination to establish a behavioral model of lysergic acid diethylamide (LSD) tolerance and examined whether tolerance to the stimulus properties of LSD is related to altered serotonin receptor signaling. Rats were trained to discriminate 60 microg/kg LSD from saline in a two-lever drug discrimination paradigm. Two groups of animals were assigned to either chronic saline treatment or chronic LSD treatment. For chronic treatment, rats from each group were injected once per day with either 130 microg/kg LSD or saline for 5 days. Rats were tested for their ability to discriminate either saline or 60 microg/kg LSD, 24 h after the last chronic injection. Rats receiving chronic LSD showed a 44% reduction in LSD lever selection, while rats receiving chronic vehicle showed no change in percent choice on the LSD lever. In another group of rats receiving the identical chronic LSD treatment, LSD-stimulated [35S]GTPgammaS binding, an index of G-protein coupling, was measured in the rat brain by autoradiography. After chronic LSD, a significant reduction in LSD-stimulated [35S]GTPgammaS binding was observed in the medial prefrontal cortex and anterior cingulate cortex. Furthermore, chronic LSD produced a significant reduction in 2,5-dimethoxy-4-iodoamphetamine-stimulated [35S]GTPgammaS binding in medial prefrontal cortex and anterior cingulate cortex, which was blocked by MDL 100907, a selective 5-HT2A receptor antagonist, but not SB206553, a 5-HT2C receptor antagonist, indicating a reduction in 5-HT2A receptor signaling. 125I-LSD binding to 5-HT2A receptors was reduced in cortical regions, demonstrating a reduction in 5-HT2A receptor density. Taken together, these results indicate that adaptive changes in LSD-stimulated serotonin receptor signaling may mediate tolerance

  5. Tezosentan reduces the microvascular filtration coefficient in isolated lungs from rats subjected to cecum ligation and puncture.

    Science.gov (United States)

    Kuklin, Vladimir; Sovershaev, Mikhail; Andreasen, Thomas; Skogen, Vegard; Ytrehus, Kirsti; Bjertnaes, Lars

    2005-01-01

    We recently demonstrated that the non-selective endothelin-1 (ET-1) receptor blocker tezosentan antagonizes ovine acute lung injury (ALI) following infusion of endotoxin or ET-1 by reducing the enhanced lung microvascular pressure, although we could not exclude the possibility of a simultaneous decline in microvascular permeability. In the present study, our aim was to find out if tezosentan reverses the rise in microvascular filtration coefficient (Kfc) in rat lungs that have been isolated and perfused 12 h after cecum ligation and puncture (CLP) or infusion of ET-1. Wistar rats (n = 42) were subjected to CLP. Postoperatively, rats were randomized to a CLP group (n = 7) and a CLP + tezosentan group (n = 7); the latter received tezosentan 30 mg/kg. A sham-operated group (n = 5) underwent laparotomy without CLP. Twelve hours postoperatively, the lungs were isolated and perfused with blood from similarly treated rats that also were used to assess plasma concentration of ET-1 and protein kinase Calpha (PKCalpha) in lung tissue. Additionally, isolated blood perfused lungs from healthy rats were randomized to a control group (n = 8), an ET-1 group (n = 7) subjected to pulmonary arterial injection of ET-1 10 nM, and an ET-1 + tezosentan group (n = 7) that received tezosentan 30 mg/kg. All lung preparations received papaverine 0.1 microg/kg added to the perfusate for vasoplegia. Pulmonary hemodynamic variables, Kfc and lung compliance (CL) were assessed. After CLP, the plasma concentration of ET-1 increased. Papaverine abolished the vasoconstrictor response to ET-1 and the pulmonary vascular pressures remained close to baseline throughout the experiments. Both CLP and injection of ET-1 caused significant changes in Kfc and CL that were prevented in tezosentan-treated rats. Compared to sham-operated animals, CLP increased the content of PKCalpha by 50% and 70% in the cytosolic and the membrane fractions of lung tissue homogenates, respectively. Tezosentan prevented the

  6. Vitamin D insufficiency reduces the protective effect of bisphosphonate on ovariectomy-induced bone loss in rats.

    Science.gov (United States)

    Mastaglia, Silvina R; Pellegrini, Gretel G; Mandalunis, Patricia M; Gonzales Chaves, Macarena M; Friedman, Silvia M; Zeni, Susana N

    2006-10-01

    The present study was carried out to obtain an experimental model of vitamin D (vit D) insufficiency and established osteopenia (experiment 1) to then investigate whether vit D status, i.e. normal or insufficient, interferes with bone mass recovery resulting from bisphosphonate therapy (experiment 2). Rats (n = 40) underwent OVX (n = 32) or a sham operation (n = 8). The first 15 days post-surgery, all groups were kept under fluorescent tube lighting and fed a diet containing 200 IU% vit D (+D). They were then assigned during an additional 45 days to receive either +D or a diet lacking vit D (-D) and kept under 12 h light/dark cycles using fluorescent or red lighting. Serum 25HOD was significantly lower in -D rats (P < 0.0001). The type of lighting did not induce differences in 25OHD, calcium (sCa), phosphorus (sP), bone alkaline phosphatase (b-AL), CTX, bone density or histology. No osteoid was observed in undecalcified bone sections. Experiment 2 (105 days): rats were fed either +D or -D according to experiment 1 and were treated with either placebo or 16 mug olpadronate (OPD)/100 g rat/week during the last 45 days. Whereas 25HOD was significantly lower (P < 0.0001) in -D/OPD than in +D/OPD rats, no significant differences in sCa, sP, b-AL or CTX were observed. OPD prevented the loss of lumbar spine (LS) and proximal tibia (PT) BMD and the decrease in bone volume (BV/TV) (P < 0.05) and in the number of trabeculae observed in untreated rats. However, +D/OPD animals presented significantly higher values of LS BMD, PT BMD and BV/TV than -D/OPD rats (P < 0.05). No osteoid was observed in undecalcified sections of bone. In summary, this is the first experimental study to provide evidence that differences in vit D status may affect the anticatabolic response to bisphosphonate treatment. However, the molecular mechanism through which vit D insufficiency reduces the effect of the aminobisphosphonate remains to be defined.

  7. Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats

    International Nuclear Information System (INIS)

    Schwartz, M.W.; Figlewicz, D.F.; Kahn, S.E.; Baskin, D.G.; Greenwood, M.R.; Porte, D. Jr.

    1990-01-01

    In order to study the role of plasma insulin in regulating the binding of insulin to the endothelium of the blood-brain barrier (BBB), insulin binding to a purified preparation of brain capillaries was measured in both genetically obese Zucker rats and lean Zucker controls. We found a reduction of 65% in brain capillary insulin binding site number in the obese compared to lean rats with no change in receptor affinity. Furthermore, specific insulin binding to brain capillaries was negatively correlated (p less than 0.05) to the plasma insulin level, suggesting a role for plasma insulin in regulating insulin binding. A similar relationship was observed between insulin receptor number in liver membranes and the plasma insulin level. We conclude that obese, hyperinsulinemic Zucker rats exhibit a reduction in the number of BBB insulin receptors, which parallels the reduction seen in other peripheral tissues. Since insulin receptors have been hypothesized to participate in the transport of insulin across the BBB, the reduction observed in the obese rats may account for the decrease in cerebrospinal fluid insulin uptake previously demonstrated in these animals

  8. Increasing intake of soybean protein or casein, but not cod meal, reduces nephrocalcinosis in female rats.

    NARCIS (Netherlands)

    Zhang, X.; Beynen, A.C.

    1992-01-01

    Female weanling rats were fed diets with soybean protein, casein or cod meal at 171, 342 or 513 mmol nitrogen/100 g for 3 wk. The diets were isonitrogenous and balanced for fat, cholesterol, calcium, magnesium and phosphorus. Cod meal feeding at 171 and 342 mmol nitrogen/100 g diet produced lower

  9. IPRODIONE DELAYS MALE RAT PUBERTAL DEVELOPMENT, REDUCING SERUM TESTOSTERONE AND EX VIVO TESTOSTERONE PRODUCTION

    Science.gov (United States)

    Iprodione (IPRO) is a dichlorophenyl dicarboximide fungicide similar to the androgen receptor (AR) antagonist vinclozolin. The current studies were designed to determine if IPRO would delay male rat pubertal development like vinclozolin and to identify the mechanism(s) of action...

  10. Sleep restriction in rats leads to changes in operant behaviour indicative of reduced prefrontal cortex function

    NARCIS (Netherlands)

    Kamphuis, Jeanine; Baichel, Swetlana; Lancel, Marike; De Boer, Sietse F.; Koolhaas, Jaap M.; Meerlo, Peter

    Sleep deprivation has profound effects on cognitive performance, and some of these effects may be mediated by impaired prefrontal cortex function. In search of an animal model to investigate this relationship we studied the influence of restricted sleep on operant conditioning in rats, particularly

  11. Chronic Oral Capsaicin Exposure During Development Leads to Adult Rats with Reduced Taste Bud Volumes.

    Science.gov (United States)

    Omelian, Jacquelyn M; Samson, Kaeli K; Sollars, Suzanne I

    2016-09-01

    Cross-sensory interaction between gustatory and trigeminal nerves occurs in the anterior tongue. Surgical manipulations have demonstrated that the strength of this relationship varies across development. Capsaicin is a neurotoxin that affects fibers of the somatosensory lingual nerve surrounding taste buds, but not fibers of the gustatory chorda tympani nerve which synapse with taste receptor cells. Since capsaicin is commonly consumed by many species, including humans, experimental use of this neurotoxin provides a naturalistic perturbation of the lingual trigeminal system. Neonatal or adults rats consumed oral capsaicin for 40 days and we examined the cross-sensory effect on the morphology of taste buds across development. Rats received moderate doses of oral capsaicin, with chronic treatments occurring either before or after taste system maturation. Tongue morphology was examined either 2 or 50 days after treatment cessation. Edema, which has been previously suggested as a cause of changes in capsaicin-related gustatory function, was also assessed. Reductions in taste bud volume occurred 50 days, but not 2 days post-treatment for rats treated as neonates. Adult rats at either time post-treatment were unaffected. Edema was not found to occur with the 5 ppm concentration of capsaicin we used. Results further elucidate the cooperative relationship between these discrete sensory systems and highlight the developmentally mediated aspect of this interaction. Chronic exposure to even moderate levels of noxious stimuli during development has the ability to impact the orosensory environment, and these changes may not be evident until long after exposure has ceased.

  12. Reduced neurophysin immunoreactivity in rat suprachiasmatic nucleus parallels dissociation of circadian feeding rhythm in constant light

    NARCIS (Netherlands)

    Steinhorst, B; Mai, JK; Rietveld, WJ

    Several distinct neuronal populations can be outlined in the suprachiasmatic nucleus (SCN) by employing immunohistochemistry. Understanding their interaction may serve as the key to the proc esses involved in the generation of circadian rhythms by the SCN. 15 adult rats were exposed to constant dim

  13. Twenty-four hours hypothermia has temporary efficacy in reducing brain infarction and inflammation in aged rats

    DEFF Research Database (Denmark)

    Sandu, Raluca Elena; Buga, Ana Maria; Balseanu, Adrian Tudor

    2016-01-01

    in aged animals. Because the duration of hypothermia in most clinical trials is between 24 and 48 hours, we questioned whether 24 hours exposure to gaseous hypothermia confers the same neuroprotective efficacy as 48 hours exposure. We found that a shorter exposure to hypothermia transiently reduced both...... inflammation and infarct size. However, after 1 week, the infarct size became even larger than in controls and after 2 weeks there was no beneficial effect on regenerative processes such as neurogenesis. Behaviorally, hypothermia also had a limited beneficial effect. Finally, after hydrogen sulfide......-induced hypothermia, the poststroke aged rats experienced a persistent sleep impairment during their active nocturnal period. Our data suggest that cellular events that are delayed by hypothermia in aged rats may, in the long term, rebound, and diminish the beneficial effects....

  14. Non-Competitive NMDA Receptor Antagonist Hemantane Reduces Ethanol Consumption in Long-Term Alcohol Experienced Rats.

    Science.gov (United States)

    Kolik, L G; Nadorova, A V; Seredenin, S B

    2017-12-01

    Activity of hemantane, an amino adamantane derivative, exhibiting the properties of lowaffinity non-competitive NMDA receptor antagonist, was evaluated in experimental in vivo models of alcoholism. Hemantane had no effects on the formation and manifestation of behavioral sensitization to ethanol in DBA/2 mice. Under conditions of free choice between 10% ethanol and water, hemantane (20 mg/kg/day for 14 days, intraperitoneally) significantly reduced the daily ethanol intake in random-bred male rats with formed alcohol motivation (>4 g/kg of ethanol). During modelling of withdrawal syndrome, hemantane administered intraperitoneally in doses of 5-20 mg/kg dose-dependently attenuated alcohol-deprivation effect after acute withdrawal with no effects on protracted abstinence. It was found that hemantane suppressed alcohol drinking behavior in long-term ethanol experienced rats and attenuated alcohol-seeking behavior after acute withdrawal.

  15. Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats

    Directory of Open Access Journals (Sweden)

    T.C. Peixoto

    2018-04-01

    Full Text Available Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

  16. Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats.

    Science.gov (United States)

    Peixoto, T C; Moura, E G; Oliveira, E; Younes-Rapozo, V; Soares, P N; Rodrigues, V S T; Santos, T R; Peixoto-Silva, N; Carvalho, J C; Calvino, C; Conceição, E P S; Guarda, D S; Claudio-Neto, S; Manhães, A C; Lisboa, P C

    2018-01-01

    Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

  17. Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

    Science.gov (United States)

    Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

    2018-01-01

    Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is likely

  18. Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

    Directory of Open Access Journals (Sweden)

    Dávid Csabai

    2018-01-01

    Full Text Available Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I and symmetric (Type II synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network

  19. Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats

    Directory of Open Access Journals (Sweden)

    Li Jianjun

    2012-09-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs possess potent immunomodulatory properties and simultaneously lack the ability to illicit immune responses. Hence, MSCs have emerged as a promising candidate for cellular therapeutics for inflammatory diseases. Within the context of this study, we investigated whether human umbilical cord-derived mesenchymal stem cells (UC-MSCs could ameliorate lipopolysaccharide- (LPS- induced acute lung injury (ALI in a rat model. Methods ALI was induced via injection of LPS. Rats were divided into three groups: (1 saline group(control, (2 LPS group, and (3 MSC + LPS group. The rats were sacrificed at 6, 24, and 48 hours after injection. Serum, bronchoalveolar lavage fluid (BALF, and lungs were collected for cytokine concentration measurements, assessment of lung injury, and histology. Results UC-MSCs increased survival rate and suppressed LPS-induced increase of serum concentrations of pro-inflammatory mediators TNF-α, IL-1β, and IL-6 without decreasing the level of anti-inflammatory cytokine IL-10. The MSC + LPS group exhibited significant improvements in lung inflammation, injury, edema, lung wet/dry ratio, protein concentration, and neutrophil counts in the BALF, as well as improved myeloperoxidase (MPO activity in the lung tissue. Furthermore, UC-MSCs decreased malondialdehyde (MDA production and increased Heme Oxygenase-1 (HO-1 protein production and activity in the lung tissue. Conclusion UC-MSCs noticeably increased the survival rate of rats suffering from LPS-induced lung injury and significantly reduced systemic and pulmonary inflammation. Promoting anti-inflammatory homeostasis and reducing oxidative stress might be the therapeutic basis of UC-MSCs.

  20. The chemopreventive potential of Curcuma purpurascens rhizome in reducing azoxymethane-induced aberrant crypt foci in rats

    Science.gov (United States)

    Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Al-Henhena, Nawal; Kunasegaran, Thubasni; Hasanpourghadi, Mohadeseh; Looi, Chung Yeng; Abd Malek, Sri Nurestri; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

    2015-01-01

    Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation

  1. Pregabalin reduces acute inflammatory and persistent pain associated with nerve injury and cancer in rat models of orofacial pain.

    Science.gov (United States)

    Hummig, Wagner; Kopruszinski, Caroline Machado; Chichorro, Juliana Geremias

    2014-01-01

    To assess the analgesic effect of pregabalin in orofacial models of acute inflammatory pain and of persistent pain associated with nerve injury and cancer, and so determine its effectiveness in controlling orofacial pains having different underlying mechanisms. Orofacial capsaicin and formalin tests were employed in male Wistar rats to assess the influence of pregabalin (or vehicle) pretreatment in acute pain models, and the results from these experiments were analyzed by one-way analysis of variance (ANOVA) followed by Newman Keuls post-hoc test. Pregabalin (or vehicle) treatment was also tested on the facial heat hyperalgesia that was evaluated in rats receiving injection of the inflammatory irritant carrageenan into the upper lip, as well as after constriction of the infraorbital nerve (a model of trigeminal neuropathic pain), or after inoculation of tumor cells into the facial vibrissal pad; two-way repeated measures ANOVA followed by Newman-Keuls post-hoc test was used to analyze data from these experiments. Facial grooming induced by capsaicin was abolished by pretreatment with pregabalin at 10 and 30 mg/kg. However, pregabalin failed to modify the first phase of the formalin response, but reduced the second phase at both doses (10 and 30 mg/kg). In addition, treatment of rats with pregabalin reduced the heat hyperalgesia induced by carrageenan, as well as by nerve injury and facial cancer. Pregabalin produced a marked antinociceptive effect in rat models of facial inflammatory pain as well as in facial neuropathic and cancer pain models, suggesting that it may represent an important agent for the clinical control of orofacial pain.

  2. Acute treatment with docosahexaenoic acid complexed to albumin reduces injury after a permanent focal cerebral ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Tiffany N Eady

    Full Text Available Docosahexaenoic acid complexed to albumin (DHA-Alb is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo, but whether a similar effect occurs in permanent MCAo is unknown. Male Sprague-Dawley rats (270-330 g underwent permanent MCAo. Neurological function was evaluated on days 1, 2 and 3 after MCAo. We studied six groups: DHA (5 mg/kg, Alb (0.63 or 1.25 g/kg, DHA-Alb (5 mg/kg+0.63 g/kg or 5 mg/kg+1.25 g/kg or saline. Treatment was administered i.v. at 3 h after onset of stroke (n = 7-10 per group. Ex vivo imaging of brains and histopathology were conducted on day 3. Saline- and Alb-treated rats developed severe neurological deficits but were not significantly different from one another. In contrast, rats treated with low and moderate doses of DHA-Alb showed improved neurological score compared to corresponding Alb groups on days 2 and 3. Total, cortical and subcortical lesion volumes computed from T2 weighted images were reduced following a moderate dose of DHA-Alb (1.25 g/kg by 25%, 22%, 34%, respectively, compared to the Alb group. The total corrected, cortical and subcortical infarct volumes were reduced by low (by 36-40% and moderate doses (by 34-42% of DHA-Alb treatment compared to the Alb groups. In conclusion, DHA-Alb therapy is highly neuroprotective in permanent MCAo in rats. This treatment can provide the basis for future therapeutics for patients suffering from ischemic stroke.

  3. Chronic Electrical Stimulation at Acupoints Reduces Body Weight and Improves Blood Glucose in Obese Rats via Autonomic Pathway.

    Science.gov (United States)

    Liu, Jiemin; Jin, Haifeng; Foreman, Robert D; Lei, Yong; Xu, Xiaohong; Li, Shiying; Yin, Jieyun; Chen, Jiande D Z

    2015-07-01

    The aim of this study was to investigate effects and mechanisms of chronic electrical stimulation at acupoints (CEA) using surgically implanted electrodes on food intake, body weight, and metabolisms in diet-induced obese (DIO) rats. Thirty-six DIO rats were chronically implanted with electrodes at acupoints ST-36 (Zusanli). Three sets of parameters were tested: electrical acupuncture (EA) 1 (2-s on, 3-s off, 0.5 ms, 15 Hz, 6 mA), EA2 (same as EA1 but continuous pulses), and EA3 (same as EA2 but 10 mA). A chronic study was then performed to investigate the effects of CEA on body weight and mechanisms involving gastrointestinal hormones and autonomic functions. EA2 significantly reduced food intake without uncomfortable behaviors. CEA at EA2 reduced body weight and epididymal fat pad weight (P fasting plasma level of glucagon-like peptide-1 (GLP-1) and peptide YY (P < 0.05); the increase of GLP-1 was inversely correlated with postprandial blood glucose (R (2) = 0.89, P < 0.05); and the plasma ghrelin level remained unchanged. EA increased sympathetic activity (P < 0.01) and reduced vagal activity (P < 0.01). CEA at ST-36 reduces body weight and improves blood glucose possibly attributed to multiple mechanisms involving gastrointestinal motility and hormones via the autonomic pathway.

  4. Nitric oxide-releasing flurbiprofen reduces formation of proinflammatory hydrogen sulfide in lipopolysaccharide-treated rat

    Science.gov (United States)

    Anuar, Farhana; Whiteman, Matthew; Siau, Jia Ling; Kwong, Shing Erl; Bhatia, Madhav; Moore, Philip K

    2006-01-01

    The biosynthesis of both nitric oxide (NO) and hydrogen sulfide (H2S) is increased in lipopolysaccharide (LPS)-injected mice and rats but their interaction in these models is not known. In this study we examined the effect of the NO donor, nitroflurbiprofen (and the parent molecule flurbiprofen) on NO and H2S metabolism in tissues from LPS-pretreated rats. Administration of LPS (10 mg kg−1, i.p.; 6 h) resulted in an increase (PFlurbiprofen (21 mg kg−1, i.p.) was without effect. These results show for the first time that nitroflurbiprofen downregulates the biosynthesis of proinflammatory H2S and suggest that such an effect may contribute to the augmented anti-inflammatory activity of this compound. These data also highlight the existence of ‘crosstalk' between NO and H2S in this model of endotoxic shock. PMID:16491094

  5. Effector stage CC chemokine receptor-1 selective antagonism reduces multiple sclerosis-like rat disease.

    Science.gov (United States)

    Eltayeb, Sana; Sunnemark, Dan; Berg, Anna-Lena; Nordvall, Gunnar; Malmberg, Asa; Lassmann, Hans; Wallström, Erik; Olsson, Tomas; Ericsson-Dahlstrand, Anders

    2003-09-01

    We have studied the role of the chemokine receptor CCR1 during the effector stage of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in DA rats. In situ hybridization histochemistry revealed local production of the CCR1 ligands CCL3 (MIP-1 alpha) and CCL5 (RANTES), as well as large numbers of CCR1 and CCR5 expressing cells within inflammatory brain lesions. A low-molecular weight CCR1 selective antagonist potently abrogated both clinical and histopathological disease signs during a 5-day treatment period, without signs of peripheral immune compromise. Thus, we demonstrate therapeutic targeting of CCR1-dependent leukocyte recruitment to the central nervous system in a multiple sclerosis (MS)-like rat model.

  6. Ethylene oxide gas sterilization does not reduce the osteoinductive potential of demineralized bone in rats

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Bang, G

    1995-01-01

    It has been shown that different sterilization procedures of demineralized bone may influence its osteoinductive properties. The aim of this study was to evaluate the effect of ethylene oxide sterilization for 1, 3, and 6 hours on the osteoinductive potential of allogeneic demineralized bone...... implanted heterotopically in rats. Sixty male Wistar rats were randomly assigned to one of four groups, A through D, and four demineralized bone chips (2.8 mg) were implanted in a pouch created between the right oblique abdominal muscles in each animal. In Group A, the demineralized bone was implanted...... without prior sterilization of the material, whereas the demineralized bone implanted in Groups B, C, and D had been sterilized in ethylene oxide gas for 1, 3, or 6 hours, respectively, and aerated for 48 hours. At 4 weeks postoperatively, bone formation was evaluated quantitatively by strontium 85 uptake...

  7. Toxoplasma gondii infection reduces predator aversion in rats through epigenetic modulation in the host medial amygdala.

    Science.gov (United States)

    Hari Dass, Shantala Arundhati; Vyas, Ajai

    2014-12-01

    Male rats (Rattus novergicus) infected with protozoan Toxoplasma gondii relinquish their innate aversion to the cat odours. This behavioural change is postulated to increase transmission of the parasite to its definitive felid hosts. Here, we show that the Toxoplasma gondii infection institutes an epigenetic change in the DNA methylation of the arginine vasopressin promoter in the medial amygdala of male rats. Infected animals exhibit hypomethylation of arginine vasopressin promoter, leading to greater expression of this nonapeptide. The infection also results in the greater activation of the vasopressinergic neurons after exposure to the cat odour. Furthermore, we show that loss of fear in the infected animals can be rescued by the systemic hypermethylation and recapitulated by directed hypomethylation in the medial amygdala. These results demonstrate an epigenetic proximate mechanism underlying the extended phenotype in the Rattus novergicus-Toxoplasma gondii association. © 2014 John Wiley & Sons Ltd.

  8. Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury.

    Science.gov (United States)

    Lee, Yee-Shuan; Funk, Lucy H; Lee, Jae K; Bunge, Mary Bartlett

    2018-04-01

    Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury (SCI) and is currently in clinical trials. In our continuing efforts to improve Schwann cell transplantation strategies, we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion. Since macrophages are major inflammatory contributors to the acute spinal cord injury, and are the major phagocytic cells, we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI. To test this hypothesis, rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not. In rat subjected to macrophage depletion, liposomes filled with clodronate were intraperitoneally injected at 1, 3, 6, 11, and 18 days post injury. Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline. Schwann cells were transplanted 1 week post injury in all rats. Biotinylated dextran amine (BDA) was injected at thoracic level 5 to evalute axon regeneration. The Basso, Beattie, and Bresnahan locomotor test, Gridwalk test, and sensory test using von Frey filaments were performed to assess functional recovery. Immunohistochemistry was used to detect glial fibrillary acidic protein, neurofilament, and green fluorescent protein (GFP), and also to visulize BDA-labelled axons. The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides. The numbers of BDA-positive axons were also quantified. At 8 weeks after Schwann cell transplantation, there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone. These changes were not associated, however, with improved Schwann cell survival, axon growth, or locomotor recovery. Although combining Schwann cell transplantation with macrophage

  9. Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury

    Science.gov (United States)

    Lee, Yee-Shuan; Funk, Lucy H.; Lee, Jae K.; Bunge, Mary Bartlett

    2018-01-01

    Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury (SCI) and is currently in clinical trials. In our continuing efforts to improve Schwann cell transplantation strategies, we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion. Since macrophages are major inflammatory contributors to the acute spinal cord injury, and are the major phagocytic cells, we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI. To test this hypothesis, rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not. In rat subjected to macrophage depletion, liposomes filled with clodronate were intraperitoneally injected at 1, 3, 6, 11, and 18 days post injury. Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline. Schwann cells were transplanted 1 week post injury in all rats. Biotinylated dextran amine (BDA) was injected at thoracic level 5 to evalute axon regeneration. The Basso, Beattie, and Bresnahan locomotor test, Gridwalk test, and sensory test using von Frey filaments were performed to assess functional recovery. Immunohistochemistry was used to detect glial fibrillary acidic protein, neurofilament, and green fluorescent protein (GFP), and also to visulize BDA-labelled axons. The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides. The numbers of BDA-positive axons were also quantified. At 8 weeks after Schwann cell transplantation, there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone. These changes were not associated, however, with improved Schwann cell survival, axon growth, or locomotor recovery. Although combining Schwann cell transplantation with macrophage

  10. Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury

    Directory of Open Access Journals (Sweden)

    Yee-Shuan Lee

    2018-01-01

    Full Text Available Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury (SCI and is currently in clinical trials. In our continuing efforts to improve Schwann cell transplantation strategies, we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion. Since macrophages are major inflammatory contributors to the acute spinal cord injury, and are the major phagocytic cells, we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI. To test this hypothesis, rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not. In rat subjected to macrophage depletion, liposomes filled with clodronate were intraperitoneally injected at 1, 3, 6, 11, and 18 days post injury. Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline. Schwann cells were transplanted 1 week post injury in all rats. Biotinylated dextran amine (BDA was injected at thoracic level 5 to evalute axon regeneration. The Basso, Beattie, and Bresnahan locomotor test, Gridwalk test, and sensory test using von Frey filaments were performed to assess functional recovery. Immunohistochemistry was used to detect glial fibrillary acidic protein, neurofilament, and green fluorescent protein (GFP, and also to visulize BDA-labelled axons. The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides. The numbers of BDA-positive axons were also quantified. At 8 weeks after Schwann cell transplantation, there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone. These changes were not associated, however, with improved Schwann cell survival, axon growth, or locomotor recovery. Although combining Schwann cell transplantation with

  11. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

    OpenAIRE

    Tawa, N E; Odessey, R; Goldberg, A L

    1997-01-01

    Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlyso...

  12. Mesenchymal Stem Cells Reduce Left Ventricular Mass in Rats with Doxorubicin-Induced Cardiomyopathy

    OpenAIRE

    Haydardedeoglu, Ali Evren; Boztok Özgermen, Deva Basak; Yavuz, Orhan

    2018-01-01

    SUMMARY: Doxorubicin is a drug that used by a majority in the treatment of carcinomas. The most obvious known side effect is cardiomyopathy. Many studies have been carried out to eliminate side effects of the doxorubicin, and stem cell studies have been added in recent years. In this study, it was aimed to investigate fetal-derived mesenchymal stem cells (F-MSCs) treatment of doxorubicininduced cardiomyopathy by morphological methods. A total of 24 rats which were divided into three separate ...

  13. Vasodilatation in the rat dorsal hindpaw induced by activation of sensory neurons is reduced by Paclitaxel

    OpenAIRE

    Gracias, N.G.; Cummins, T.R.; Kelley, M.R.; Basile, D.P.; Iqbal, T.; Vasko, M.R.

    2010-01-01

    Peripheral neuropathy is a major side effect following treatment with the cancer chemotherapeutic drug paclitaxel. Whether paclitaxel-induced peripheral neuropathy is secondary to altered function of small diameter sensory neurons remains controversial. To ascertain whether the function of the small diameter sensory neurons was altered following systemic administration of paclitaxel, we injected male Sprague Dawley rats with 1 mg/kg paclitaxel every other day for a total of four doses and exa...

  14. Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats

    OpenAIRE

    Peixoto, T.C.; Moura, E.G.; Oliveira, E.; Younes-Rapozo, V.; Soares, P.N.; Rodrigues, V.S.T.; Santos, T.R.; Peixoto-Silva, N.; Carvalho, J.C.; Calvino, C.; Conceição, E.P.S.; Guarda, D.S.; Claudio-Neto, S.; Manhães, A.C.; Lisboa, P.C.

    2018-01-01

    Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower ...

  15. Information rich display design

    International Nuclear Information System (INIS)

    Welch, Robin; Braseth, Alf Ove; Veland, Oeystein

    2004-01-01

    This paper presents the concept Information Rich Displays. The purpose of Information Rich Displays (IRDs) is to condensate prevailing information in process displays in such a way that each display format (picture) contains more relevant information for the user. Compared to traditional process control displays, this new concept allows the operator to attain key information at a glance and at the same time allows for improved monitoring of larger portions of the process. This again allows for reduced navigation between both process and trend displays and ease the cognitive demand on the operator. This concept has been created while working on designing display prototypes for the offshore petroleum production facilities of tomorrow. Offshore installations basically consist of wells, separation trains (where oil, gas and water are separated from each other), an oil tax measurement system (where oil quality is measured and the pressure increased to allow for export), gas compression (compression of gas for export) and utility systems (water treatment, chemical systems etc.). This means that an offshore control room operator has to deal with a complex process that comprises several functionally different systems. The need for a new approach to offshore display format design is in particular based on shortcomings in today's designs related to the keyhole effect, where the display format only reveals a fraction of the whole process. Furthermore, the upcoming introduction of larger off- and on-shore operation centres will increase the size and complexity of the operators' work domain. In the light of the increased demands on the operator, the proposed IRDs aim to counter the negative effects this may have on the workload. In this work we have attempted to classify the wide range of different roles an operator can have in different situations. The information content and amount being presented to the operator in a display should be viewed in context of the roles the

  16. Increased Dietary Leucine Reduces Doxorubicin-Associated Cardiac Dysfunction in Rats

    Directory of Open Access Journals (Sweden)

    Thiago M. Fidale

    2018-01-01

    Full Text Available Cardiotoxicity is one of the most significant adverse effects of the oncologic treatment with doxorubicin, which is responsible for a substantial morbid and mortality. The occurrence of heart failure with ventricular dysfunction may lead to severe cardiomyopathy and ultimately to death. Studies have focused on the effects of leucine supplementation as a strategy to minimize or revert the clinical condition of induced proteolysis by several clinical onsets. However, the impact of leucine supplementation in heart failure induced by doxorubicin is unknown. Therefore, the objective of this work is to evaluate the effects of leucine supplementation on the cardiotoxicity in the heart of rats treated with doxorubicin. Rats treated with a 7.5 mg/kg cumulative dose of doxorubicin for 14 days presented a dilatation of the left ventricle (LV, and a reduction of the ejection fraction (FE. The 5% supplementation of leucine in the rats' food prevented the malfunctioning of the LV when administered with doxorubicin. Some alterations in the extracellular matrix remodeling were confirmed by the increase of collagen fibers in the doxorubicin group, which did not increase when the treatment was associated with leucine supplementation. Leucine attenuates heart failure in this experimental model with doxorubicin. Such protection is followed by the maintenance of interstitial collagen fibers.

  17. Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal magnesium serum levels.

    Science.gov (United States)

    Srebro, Dragana P; Vučković, Sonja M; Dožić, Ivan S; Dožić, Branko S; Savić Vujović, Katarina R; Milovanović, Aleksandar P; Karadžić, Branislav V; Prostran, Milica Š

    2018-02-01

    In humans, orofacial pain has a high prevalence and is often difficult to treat. Magnesium is an essential element in biological a system which controls the activity of many ion channels, neurotransmitters and enzymes. Magnesium produces an antinociceptive effect in neuropathic pain, while in inflammatory pain results are not consistent. We examined the effects of magnesium sulfate using the rat orofacial formalin test, a model of trigeminal pain. Male Wistar rats were injected with 1.5% formalin into the perinasal area, and the total time spent in pain-related behavior (face rubbing) was quantified. We also spectrophotometrically determined the concentration of magnesium and creatine kinase activity in blood serum. Magnesium sulfate administered subcutaneously (0.005-45mg/kg) produced significant antinociception in the second phase of the orofacial formalin test in rats at physiological serum concentration of magnesium. The effect was not dose-dependent. The maximum antinociceptive effect of magnesium sulfate was about 50% and was achieved at doses of 15 and 45mg/kg. Magnesium did not affect increase the levels of serum creatine kinase activity. Preemptive systemic administration of magnesium sulfate as the only drug can be used to prevent inflammatory pain in the orofacial region. Its analgesic effect is not associated with magnesium deficiency. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  18. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    Science.gov (United States)

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

  19. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

    Directory of Open Access Journals (Sweden)

    Cibele S Borges

    Full Text Available Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin

  20. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

    Science.gov (United States)

    Borges, Cibele S; Missassi, Gabriela; Pacini, Enio S A; Kiguti, Luiz Ricardo A; Sanabria, Marciana; Silva, Raquel F; Banzato, Thais P; Perobelli, Juliana E; Pupo, André S; Kempinas, Wilma G

    2013-01-01

    Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day) or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin-norepinephrine reuptake inhibitors

  1. Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

    Science.gov (United States)

    Feng, Yangzheng; LeBlanc, Michael H.; Regunathan, Soundar

    2010-01-01

    Glutamate has been implicated in the initiation and spread of seizure activity. Agmatine, an endogenous neuromodulator, is an antagonist of NMDA receptors and has anticonvulsive effects. Whether agmatine regulate glutamate release, as measured by in vivo microdialysis, is not known. In this study, we used pentylenetetrazole (PTZ)-induced seizure model to determine the effect of agmatine on extracellular glutamate in rat brain. We also determined the time course and the amount of agmatine that reached brain after peripheral injection. After i.p. injection of agmatine (50 mg/kg), increase of agmatine in rat cortex and hippocampus was observed in 15 min with levels returning to baseline in one hour. Rats, naïve and implanted with microdialysis cannula into the cortex, were administered PTZ (60 mg/kg, i.p.) with prior injection of agmatine (100 mg/kg, i.p.) or saline. Seizure grades were recorded and microdialysis samples were collected every 15 min for 75 min. Agmatine pre-treatment significantly reduced the seizure grade and increased the onset time. The levels of extracellular glutamate in frontal cortex rose two- to three-fold after PTZ injection and agmatine significantly inhibited this increase. In conclusion, the present data suggest that the anticonvulsant activity of agmatine, in part, could be related to the inhibition glutamate release. PMID:16125317

  2. Melatonin reduces lead levels in blood, brain and bone and increases lead excretion in rats subjected to subacute lead treatment.

    Science.gov (United States)

    Hernández-Plata, Everardo; Quiroz-Compeán, Fátima; Ramírez-Garcia, Gonzalo; Barrientos, Eunice Yáñez; Rodríguez-Morales, Nadia M; Flores, Alberto; Wrobel, Katarzina; Wrobel, Kazimierz; Méndez, Isabel; Díaz-Muñoz, Mauricio; Robles, Juvencio; Martínez-Alfaro, Minerva

    2015-03-04

    Melatonin, a hormone known for its effects on free radical scavenging and antioxidant activity, can reduce lead toxicity in vivo and in vitro.We examined the effects of melatonin on lead bio-distribution. Rats were intraperitoneally injected with lead acetate (10, 15 or 20mg/kg/day) with or without melatonin (10mg/kg/day) daily for 10 days. In rats intoxicated with the highest lead doses, those treated with melatonin had lower lead levels in blood and higher levels in urine and feces than those treated with lead alone, suggesting that melatonin increases lead excretion. To explore the mechanism underlying this effect, we first assessed whether lead/melatonin complexes were formed directly. Electronic density functional (DFT) calculations showed that a lead/melatonin complex is energetically feasible; however, UV spectroscopy and NMR analysis showed no evidence of such complexes. Next, we examined the liver mRNA levels of metallothioneins (MT) 1 and 2. Melatonin cotreatment increased the MT2 mRNA expression in the liver of rats that received the highest doses of lead. The potential effects of MTs on the tissue distribution and excretion of lead are not well understood. This is the first report to suggest that melatonin directly affects lead levels in organisms exposed to subacute lead intoxication. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Swimming exercise increases serum irisin level and reduces body fat mass in high-fat-diet fed Wistar rats.

    Science.gov (United States)

    Lu, Yun; Li, Hongwei; Shen, Shi-Wei; Shen, Zhen-Hai; Xu, Ming; Yang, Cheng-Jian; Li, Feng; Feng, Yin-Bo; Yun, Jing-Ting; Wang, Ling; Qi, Hua-Jin

    2016-05-13

    It has been shown that irisin levels are reduced in skeletal muscle and plasma of obese rats; however, the effect of exercise training on irisin level remains controversial. We aim to evaluate the association of swimming exercise with serum irisin level and other obesity-associated parameters. Forty healthy male Wistar rats were randomly assigned to 4 groups: a normal diet and sedentary group (ND group), normal diet and exercise group (NDE group), high-fat diet and sedentary group (HFD group), and high-fat diet and exercise group (HFDE group. After 8 consecutive weeks of swimming exercise, fat mass and serum irisin level was determined. Higher serum irisin levels were detected in the HFDE group (1.15 ± 0.28 μg/L) and NDE group (1.76 ± 0.17 μg/L) than in the HFD group (0.84 ± 0.23 μg/L) or the ND group (1.24 ± 0.29 μg/L), respectively (HFDE group vs. HFD group, P mass (r = -0.68, P mass (r = -0.576, P mass (r = -0.439, P mass, visceral fat mass and percentage fat mass were lower in the HFDE group than the HFD group (all P values mass in high-fat-fed Wistar rats, which may be attributable to elevated irisin levels induced by swimming exercise.

  4. Enhanced memory in Wistar rats by virgin coconut oil is associated with increased antioxidative, cholinergic activities and reduced oxidative stress.

    Science.gov (United States)

    Rahim, Nur Syafiqah; Lim, Siong Meng; Mani, Vasudevan; Abdul Majeed, Abu Bakar; Ramasamy, Kalavathy

    2017-12-01

    Virgin coconut oil (VCO) has been reported to possess antioxidative, anti-inflammatory and anti-stress properties. Capitalizing on these therapeutic effects, this study investigated for the first time the potential of VCO on memory improvement in vivo. Thirty male Wistar rats (7-8 weeks old) were randomly assigned to five groups (n = six per group). Treatment groups were administered with 1, 5 and 10 g/kg VCO for 31 days by oral gavages. The cognitive function of treated-rats were assessed using the Morris Water Maze Test. Brains were removed, homogenized and subjected to biochemical analyses of acetylcholine (ACh) and acetylcholinesterase (AChE), antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GRx)], lipid peroxidase [malondialdehyde (MDA)] as well as nitric oxide (NO). α-Tocopherol (αT; 150 mg/kg) was also included for comparison purposes. VCO-fed Wistar rats exhibited significant (p  33%) and NO (≥ 34%). Overall, memory improvement by VCO was comparable to αT. VCO has the potential to be used as a memory enhancer, the effect of which was mediated, at least in part, through enhanced cholinergic activity, increased antioxidants level and reduced oxidative stress.

  5. A Phospholipid-Protein Complex from Krill with Antioxidative and Immunomodulating Properties Reduced Plasma Triacylglycerol and Hepatic Lipogenesis in Rats

    Directory of Open Access Journals (Sweden)

    Marie S. Ramsvik

    2015-07-01

    Full Text Available Dietary intake of marine omega-3 polyunsaturated fatty acids (n-3 PUFAs can change the plasma profile from atherogenic to cardioprotective. In addition, there is growing evidence that proteins of marine origin may have health benefits. We investigated a phospholipid-protein complex (PPC from krill that is hypothesized to influence lipid metabolism, inflammation, and redox status. Male Wistar rats were fed a control diet (2% soy oil, 8% lard, 20% casein, or diets where corresponding amounts of casein and lard were replaced with PPC at 3%, 6%, or 11% (wt %, for four weeks. Dietary supplementation with PPC resulted in significantly lower levels of plasma triacylglycerols in the 11% PPC-fed group, probably due to reduced hepatic lipogenesis. Plasma cholesterol levels were also reduced at the highest dose of PPC. In addition, the plasma and liver content of n-3 PUFAs increased while n-6 PUFAs decreased. This was associated with increased total antioxidant capacity in plasma and increased liver gene expression of mitochondrial superoxide dismutase (Sod2. Finally, a reduced plasma level of the inflammatory mediator interleukin-2 (IL-2 was detected in the PPC-fed animals. The present data show that PPC has lipid-lowering effects in rats, and may modulate risk factors related to cardiovascular disease progression.

  6. A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance.

    Science.gov (United States)

    Bosse, John D; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E Dale; Pereira, Troy J; Dolinsky, Vernon W; Symons, J David; Jalili, Thunder

    2013-06-15

    Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-HF had lower (P vs. 159 ± 3 mmHg) but a similar degree of cardiac hypertrophy (33.4 ± 0.4 vs. 33.1 ± 0.4 heart weight/tibia length, mg/mm). Mesenteric arteries and the entire aorta were used to assess vascular function and endothelial nitric oxide synthase (eNOS) signaling, respectively. Endothelium-dependent (acetylcholine) relaxation of mesenteric arteries was improved (P vs. SHR-C, whereas contraction (potassium chloride, phenylephrine) was reduced (P vs. SHR-C. Plasma glucose, insulin, and homoeostatic model of insulin assessment were lower (P vs. SHR-C, whereas peripheral insulin sensitivity (insulin tolerance test) was similar. After a 10-h fast, insulin stimulation (2 U/kg ip) increased (P vs. SHR-HF. In conclusion, a low-carbohydrate/high-fat diet reduced blood pressure and improved arterial function in SHR without producing signs of insulin resistance or altering insulin-mediated signaling in the heart, skeletal muscle, or vasculature.

  7. Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

    Science.gov (United States)

    Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

    2013-12-01

    Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

  8. Fructose-enriched diet induces inflammation and reduces antioxidative defense in visceral adipose tissue of young female rats.

    Science.gov (United States)

    Kovačević, Sanja; Nestorov, Jelena; Matić, Gordana; Elaković, Ivana

    2017-02-01

    The consumption of refined, fructose-enriched food continuously increases and has been linked to development of obesity, especially in young population. Low-grade inflammation and increased oxidative stress have been implicated in the pathogenesis of obesity-related disorders including type 2 diabetes. In this study, we examined alterations in inflammation and antioxidative defense system in the visceral adipose tissue (VAT) of fructose-fed young female rats, and related them to changes in adiposity and insulin sensitivity. We examined the effects of 9-week fructose-enriched diet applied immediately after weaning on nuclear factor κB (NF-κB) intracellular distribution, and on the expression of pro-inflammatory cytokines (IL-1β and TNFα) and key antioxidative enzymes in the VAT of female rats. Insulin signaling in the VAT was evaluated at the level of insulin receptor substrate-1 (IRS-1) protein and its inhibitory phosphorylation on Ser 307 . Fructose-fed rats had increased VAT mass along with increased NF-κB nuclear accumulation and elevated IL-1β, but not TNFα expression. The protein levels of antioxidative defense enzymes, mitochondrial manganese superoxide dismutase 2, and glutathione peroxidase, were reduced, while the protein content of IRS-1 and its inhibitory phosphorylation were not altered by fructose diet. The results suggest that fructose overconsumption-related alterations in pro-inflammatory markers and antioxidative capacity in the VAT of young female rats can be implicated in the development of adiposity, but do not affect inhibitory phosphorylation of IRS-1.

  9. Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)

    International Nuclear Information System (INIS)

    Fonsart, Julien; Menet, Marie-Claude; Decleves, Xavier; Galons, Herve; Crete, Dominique; Debray, Marcel; Scherrmann, Jean-Michel; Noble, Florence

    2008-01-01

    The use of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been associated with unexplained deaths. Male humans and rodents are more sensitive to acute toxicity than are females, including a potentially lethal hyperthermia. MDMA is highly metabolized to five main metabolites, by the enzymes CYP1A2 and CYP2D. The major metabolite in rats, 3,4-methylenedioxyamphetamine (MDA), also causes hyperthermia. We postulated that the reported sex difference in rats is due to a sexual dimorphism(s). We therefore determined (1) the LD50 of MDMA and MDA, (2) their hyperthermic effects, (3) the activities of liver CYP1A2 and CYP2D, (4) the liver microsomal metabolism of MDMA and MDA, (5) and the plasma concentrations of MDMA and its metabolites 3 h after giving male and female Sprague-Dawley (SD) rats MDMA (5 mg.kg -1 sc). The LD50 of MDMA was 2.4-times lower in males than in females. MDMA induced greater hyperthermia (0.9 deg. C) in males. The plasma MDA concentration was 1.3-fold higher in males, as were CYP1A2 activity (twice) and N-demethylation to MDA (3.3-fold), but the plasma MDMA concentration (1.4-fold) and CYP2D activity (1.3-fold) were higher in females. These results suggest that male SD rats are more sensitive to MDMA acute toxicity than are females, probably because their CYP1A2 is more active, leading to higher N-demethylation and plasma MDA concentration. This metabolic pathway could be responsible for the lethality of MDMA, as the LD50 of MDA is the same in both sexes. These data strongly suggest that the toxicity of amphetamine-related drugs largely depends on metabolic differences

  10. Aqueous Extract of Phyllanthus niruri Leaves Displays In Vitro Antioxidant Activity and Prevents the Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats

    Directory of Open Access Journals (Sweden)

    Nelli Giribabu

    2014-01-01

    Full Text Available P. niruri has been reported to possess antidiabetic and kidney protective effects. In the present study, the phytochemical constituents and in vitro antioxidant activity of P. niruri leaf aqueous extract were investigated together with its effect on oxidative stress and antioxidant enzymes levels in diabetic rat kidney. Results. Treatment of diabetic male rats with P. niruri leaf aqueous extract (200 and 400 mg/kg for 28 consecutive days prevents the increase in the amount of lipid peroxidation (LPO product, malondialdehyde (MDA, and the diminution of superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx activity levels in the kidney of diabetic rats. The amount of LPO showed strong negative correlation with SOD, CAT, and GPx activity levels. P. niruri leaf aqueous extract exhibits in vitro antioxidant activity with IC50 slightly lower than ascorbic acid. Phytochemical screening of plant extract indicates the presence of polyphenols. Conclusion. P. niruri leaf extract protects the kidney from oxidative stress induced by diabetes.

  11. Regional blood flows in the established stage of reduced renal mass (RRM) hypertension in rats

    International Nuclear Information System (INIS)

    Smits, G.J.; Lombard, J.H.

    1986-01-01

    Regional blood flows were measured with 15 μm 153 Gd-labelled microspheres in 21 anesthetized (pentobarbital-50 mg/kg, i.p.) male Sprague Dawley rats 5-6 weeks after a 75% reduction in renal mass and in 6 sham operated controls (SOC). RRM rats were maintained on either a high salt (HS-RRM) diet, i.e., choice of 1% NaCl or tap water (n = 11), or on a salt-restricted (SR-RRM) diet (n = 10). Mean arterial blood pressure was significantly elevated (mean +/- SE) in the HS-RRM (168 +/- 5 mmHg) vs. either the SR-RRM (147 +/- 6 mmHg) or the SOC (138 +/- 4 mmHg). Although blood flow to the skin and femur were elevated in HS-RRM and SR-RRM relative to SOC, there were no significant differences in blood flow to skeletal muscle, spleen, liver, small intestine, stomach or testes between any of the groups. Absolute renal blood flow and renal blood flow/gm of tissue were significantly lower in HS-RRM (7.2 +/- 0.7 ml/min or 3.4 +/- 0.5 ml/min/gm) and SR-RRM (6.3 +/- 0.6 ml/min or 3.2 +/- 0.3 ml/min/gm) than in SOC (15.1 +/- 0.97 ml/min or 5.5 +/- 0.2 ml/min/gm). The present results suggest that regional blood flow is unchanged in most vascular beds during the established stage of RRM hypertension in rats

  12. Dietary milk fat globule membrane reduces the incidence of aberrant crypt foci in Fischer-344 rats.

    Science.gov (United States)

    Snow, Dallin R; Jimenez-Flores, Rafael; Ward, Robert E; Cambell, Jesse; Young, Michael J; Nemere, Ilka; Hintze, Korry J

    2010-02-24

    Milk fat globule membrane (MFGM) is a biopolymer composed primarily of membrane proteins and lipids that surround the fat globules in milk. Although it is considered to have potential as a bioactive ingredient, few feeding studies have been conducted to measure its potential benefits. The aim of this investigation was to determine if dietary MFGM confers protection against colon carcinogenesis compared to diets containing corn oil (CO) or anhydrous milk fat (AMF). Male, weanling Fischer-344 rats were randomly assigned to one of three dietary treatments that differed only in the fat source: (1) AIN-76A diet, corn oil; (2) AIN-76A diet, AMF; and (3) AIN-76A diet, 50% MFGM, 50% AMF. Each diet contained 50 g/kg diet of fat. With the exception of the fat source, diets were formulated to be identical in macro and micro nutrient content. Animals were injected with 1,2-dimethylhydrazine once per week at weeks 3 and 4, and fed experimental diets for a total of 13 weeks. Over the course of the study dietary treatment did not affect food consumption, weight gain or body composition. After 13 weeks animals were sacrificed, colons were removed and aberrant crypt foci (ACF) were counted by microscopy. Rats fed the MFGM diet (n = 16) had significantly fewer ACF (20.9 +/- 5.7) compared to rats fed corn oil (n = 17) or AMF (n = 16) diets (31.3 +/- 9.5 and 29.8 +/- 11.4 respectively; P < 0.05). Gene expression analysis of colonic mucosa did not reveal differential expression of candidate colon cancer genes, and the sphingolipid profile of the colonic mucosa was not affected by diet. While there were notable and significant differences in plasma and red blood cell lipids, there was no relationship to the cancer protection. These results support previous findings that dietary sphingolipids are protective against colon carcinogenesis yet extend this finding to MFGM, a milk fat fraction available as a food ingredient.

  13. Vitamin E and Hippophea rhamnoides L. extract reduce nicotine-induced oxidative stress in rat heart.

    Science.gov (United States)

    Gumustekin, Kenan; Taysi, Seyithan; Alp, Hamit Hakan; Aktas, Omer; Oztasan, Nuray; Akcay, Fatih; Suleyman, Halis; Akar, Sedat; Dane, Senol; Gul, Mustafa

    2010-06-01

    The effects of vitamin E and Hippophea rhamnoides L. extract (HRe-1) on nicotine-induced oxidative stress in rat heart were investigated. There were eight rats per group and supplementation period was 3 weeks. The groups were: nicotine [0.5 mg kg(-1)day(-1), intraperitoneal (i.p.)]; nicotine plus vitamin E [75 mg kg(-1)day(-1), intragastric (i.g.)]; nicotine plus HRe-1 (250 mg kg(-1)day(-1), i.g.); and the control group (receiving only vehicles). Nicotine increased the malondialdehyde level, which was prevented by both vitamin E and HRe-1. Glutathione peroxidase (GPx) activity in nicotine plus vitamin E supplemented group was higher than the others. Glutathione S-transferase (GST) activity in nicotine plus HRe-1 supplemented group was increased compared with the control group. Catalase activity was higher in nicotine group compared with others. GPx activity in nicotine plus vitamin E supplemented group was elevated compared with the others. Total and non-enzymatic superoxide scavenger activities in nicotine plus vitamin E supplemented group were lower than nicotine plus HRe-1 supplemented group. Superoxide dismutase (SOD) activity was higher in nicotine plus HRe-1 supplemented group compared with others. Glutathione reductase activity and nitric oxide level were not affected. Increased SOD and GST activities might have taken part in the prevention of nicotine-induced oxidative stress in HRe-1 supplemented group in rat heart. Flavonols such as quercetin, and isorahmnetin, tocopherols such as alpha-tocopherol and beta-tocopherol and carotenoids such as alpha-carotene and beta-carotene, reported to be present in H. rhamnoides L. extracts may be responsible for the antioxidant effects of this plant extract. 2010 John Wiley & Sons, Ltd.

  14. Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity

    OpenAIRE

    Kuniaki Tsutsumi; Takanori Kaname; Haruka Shiraishi; Takehiro Kawashiri; Nobuaki Egashira

    2016-01-01

    Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily) inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7) and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect th...

  15. Synchronization among Mechanisms of Renal Autoregulation is Reduced in Hypertensive Rats

    DEFF Research Database (Denmark)

    Sosnovtseva, Olga; Pavlov, A. N.; Mosekilde, Erik

    2007-01-01

    , and a slower (20-40 mHz) oscillation in tubuloglomerular feedback (TGF). These mechanisms interact; the TGF mode modulates both the amplitude and the frequency of the myogenic mode. Nephrons also communicate with each other using vascular signals triggered by membrane events in arteriolar smooth muscle cells...... in SHR is a state of partial synchronization with entrainment between neighboring nephrons for only one of the modes. Modulation of the myogenic mode by the TGF mode is much stronger in hypertensive than in normotensive rats. Synchronization among nephrons forms the basis for an integrated reaction...

  16. Glucagon-like peptide-1 analogue, liraglutide, delays onset and reduces severity of experimental autoimmune encephalitis in Lewis rats

    Directory of Open Access Journals (Sweden)

    Brian DellaValle

    2016-11-01

    Full Text Available AbstractIntroduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS pathology and influence the susceptibility to treatment, directing attention towards anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1 family, is also anti-diabetic and weight-reducing and is moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE.Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 µg/kg s.c. or saline. Healthy controls were included (saline, n=6, liraglutide, n=7. Clinical score and weight were assessed daily by blinded observers. Animals were killed at peak disease severity (day 11 or if exceeding humane endpoint (clinical score ≥4. Protein levels of manganese superoxide dismutase (MnSOD, amyloid precursor protein (APP, and glial fibrillary acidic protein (GFAP were determined.Results: Liraglutide treatment delayed disease onset (group clinical score significantly >0 by two days and markedly reduced disease severity (median clinical score 2 vs. 5; p=0.0003. Fourteen of 15 (93% of vehicle-treated rats reached the humane endpoint (clinical score ≥4 by day 11 compared to 5 of 15 (33% of liraglutide-treated rats (p=0.0004. Liraglutide substantially increased the mitochondrial antioxidant MnSOD (p<0.01 and reduced the neurodegenerative marker APP (p=0.036 in the brain. GFAP levels were not significantly changed with drug treatment (p=0.09Conclusion: We demonstrate, for the first time, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1 receptor

  17. Sertoli cell specific knockdown of RAR-related orphan receptor (ROR) alpha at puberty reduces sperm count in rats.

    Science.gov (United States)

    Mandal, Kamal; Sarkar, Rajesh K; Sen Sharma, Souvik; Jain, Ayushi; Majumdar, Subeer S

    2018-01-30

    Globally, there is an alarming decline in sperm count. Very often hormonal supplementation fails to restore normal sperm count. Sertoli cells (Sc) present within seminiferous tubules provide appropriate niche and factors required for the differentiation of germ cells (Gc) into mature sperm (spermatogenesis). Functionally compromised Sc may be one of the reasons for failure of hormones to facilitate normal spermatogenesis. Although role of secretory proteins and signaling molecules of Sc has been studied well, role of transcription factors regulating sperm count has not been addressed appropriately. Retinoic acid receptor-related orphan receptor (ROR)-alpha is one of such transcription factors reported in testis but its role in testicular function is not yet known. In a separate study, we found abundant ROR-alpha binding sites on promoter regions of several genes upregulated in pubertal rat Sc as compared to infant Sc. Immunostaining studies also revealed presence of ROR alpha in nucleus of pubertal Sc. We generated a transgenic knockdown rat model expressing shRNA targeted to ROR-alpha under Sc specific promoter, which is transcriptionally active only at and after puberty. ROR-alpha knockdown animals were found to have abnormal association of Sc and Gc, including Gc sloughing and restricted release of sperm. The knockdown animals displayed compromised spermatogenesis leading to significant reduction in sperm count. This is the first report describing the Sc specific role of ROR-alpha in maintaining quantitatively normal sperm output. Identification of various such molecules can generate avenues to limit or reverse an alarmingly declining sperm count witnessed globally in men. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Leptin receptor blockade reduces intrahepatic vascular resistance and portal pressure in an experimental model of rat liver cirrhosis.

    Science.gov (United States)

    Delgado, María Gabriela; Gracia-Sancho, Jordi; Marrone, Giusi; Rodríguez-Vilarrupla, Aina; Deulofeu, Ramon; Abraldes, Juan G; Bosch, Jaume; García-Pagán, Juan Carlos

    2013-10-01

    Increased hepatic vascular resistance mainly due to elevated vascular tone and to fibrosis is the primary factor in the development of portal hypertension in cirrhosis. Leptin, a hormone associated with reduction in nitric oxide bioavailability, vascular dysfunction, and liver fibrosis, is increased in patients with cirrhosis. We aimed at evaluating whether leptin influences the increased hepatic resistance in portal hypertension. CCl4-cirrhotic rats received the leptin receptor-blocker ObR antibody, or its vehicle, every other day for 1 wk. Hepatic and systemic hemodynamics were measured in both groups. Hepatic nitric oxide production and bioavailability, together with oxidative stress, nitrotyrosinated proteins, and liver fibrosis, were evaluated. In cirrhotic rats, leptin-receptor blockade significantly reduced portal pressure without modifying portal blood flow, suggesting a reduction in the intrahepatic resistance. Portal pressure reduction was associated with increased nitric oxide bioavailability and with decreased O2(-) levels and nitrotyrosinated proteins. No changes in systemic hemodynamics and liver fibrosis were observed. In conclusion, the present study shows that blockade of the leptin signaling pathway in cirrhosis significantly reduces portal pressure. This effect is probably due to a nitric oxide-mediated reduction in the hepatic vascular tone.

  19. Arctigenin reduces blood pressure by modulation of nitric oxide synthase and NADPH oxidase expression in spontaneously hypertensive rats.

    Science.gov (United States)

    Liu, Ying; Wang, Guoyuan; Yang, Mingguang; Chen, Haining; zhao, Yan; Yang, Shucai; Sun, Changhao

    2015-12-25

    Arctigenin is a bioactive constituent from dried seeds of Arctium lappa L., which was traditionally used as medicine. Arctigenin exhibits various bioactivities, but its effects on blood pressure regulation are still not widely studied. In this study, we investigated antihypertensive effects of arctigenin by long-term treatment in spontaneously hypertensive rats (SHRs). Arctigenin (50 mg/kg) or vehicle was administered to SHRs or Wistar rats as negative control by oral gavage once a day for total 8 weeks. Nifedipine (3 mg/kg) was used as a positive drug control. After treatment, hemodynamic and physical parameters, vascular reactivity in aorta, the concentration of plasma arctigenin and serum thromboxane B2, NO release and vascular p-eNOS, p-Akt, caveolin-1 protein expression, and vascular superoxide anion generation and p47phox protein expression were detected and analyzed. The results showed that arctigenin significantly reduced systolic blood pressure and ameliorated endothelial dysfunction of SHRs. Arctigenin reduced the levels of thromboxane B2 in plasma and superoxide anion in thoracic aorta of SHRs. Furthermore, arctigenin increased the NO production by enhancing the phosphorylation of Akt and eNOS (Ser 1177), and inhibiting the expression of NADPH oxidase in thoracic aorta of SHRs. Our data suggested that antihypertensive mechanisms of arctigenin were associated with enhanced eNOS phosphorylation and decreased NADPH oxidase-mediated superoxide anion generation. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Fish Oil Supplementation Reduces Heart Levels of Interleukin-6 in Rats with Chronic Inflammation due to Epilepsy

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    Mariana Bocca Nejm

    2017-06-01

    Full Text Available Sudden unexpected death in epilepsy (SUDEP is a major cause of premature death related to epilepsy. The causes of SUDEP remain unknown, but cardiac arrhythmias and asphyxia have been suggested as a major mechanism of this event. Inflammation has been implicated in the pathogenesis of both epilepsy and ventricular arrhythmia, with interleukin-6 (IL-6 being recognized as a crucial orchestrator of inflammatory states. Our group previously reported that levels of IL-6 were increased in the hearts of epileptic rats. In this scenario, anti-inflammatory actions are among the beneficial effects of fish oil dietary supplementation. This investigation revealed that elevated levels of IL-6 in the heart were markedly reduced in epileptic rats that were treated in the long-term with fish oil, suggesting protective anti-inflammatory actions against dangerously high levels of IL-6. Based on these findings, our results suggest beneficial effects of long-term intake of fish oil in reducing the inflammation associated with chronic epilepsy.

  1. Blooming reduces the antioxidant capacity of dark chocolate in rats without lowering its capacity to improve lipid profiles.

    Science.gov (United States)

    Shadwell, Naomi; Villalobos, Fatima; Kern, Mark; Hong, Mee Young

    2013-05-01

    Dark chocolate contains high levels of antioxidants which are linked to a reduced risk of cardiovascular disease. Chocolate blooming occurs after exposure to high temperatures. Although bloomed chocolate is safe for human consumption, it is not known whether or not the biological function of bloomed chocolate is affected. We hypothesized that bloomed chocolate would reduce the antioxidant potential and lipid-lowering properties of chocolate through altered expression of related genes. Thirty Sprague-Dawley rats were divided into 3 groups and fed either the control (CON), regular dark chocolate (RDC), or bloomed dark chocolate (BDC) diet. After 3 weeks, serum lipid levels and antioxidant capacity were measured. Hepatic expression of key genes was determined by real time polymerase chain reaction (PCR). Sensory characteristics of bloomed versus regular chocolate were assessed in 28 semi-trained panelists. Rats fed RDC exhibited greater serum antioxidant capacities compared to the CON (P chocolate compared to bloomed chocolate (P chocolate, these results suggest that bloomed dark chocolate yields similarly beneficial effects on most blood lipid parameters or biomarkers. However, regular dark chocolate may be more beneficial for the improvement of antioxidant status and modulation of gene expression involved in lipid metabolism and promoted greater sensory ratings. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Rosuvastatin reduces neointima formation in a rat model of balloon injury

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    Preusch MR

    2010-11-01

    Full Text Available Abstract Background Processes of restenosis, following arterial injury, are complex involving different cell types producing various cytokines and enzymes. Among those enzymes, smooth muscle cell-derived matrix metalloproteinases (MMPs are thought to take part in cell migration, degrading of extracellular matrix, and neointima formation. MMP-9, also known as gelatinase B, is expressed immediately after vascular injury and its expression and activity can be inhibited by statins. Using an established in vivo model of vascular injury, we investigated the effect of the HMG-CoA reductase inhibitor rosuvastatin on MMP-9 expression and neointima formation. Materials and methods 14-week old male Sprague Dawley rats underwent balloon injury of the common carotid artery. Half of the animals received rosuvastatin (20 mg/kg body weight/day via oral gavage, beginning 3 days prior to injury. Gelatinase activity and neointima formation were analyzed 3 days and 14 days after balloon injury, respectively. 14 days after vascular injury, proliferative activity was assessed by staining for Ki67. Results After 14 days, animals in the rosuvastatin group showed a decrease in total neointima formation (0.194 ± 0.01 mm2 versus 0.124 ± 0.02 mm2, p Conclusions Rosuvastatin attenuates neointima formation without affecting early MMP-9 activity in a rat model of vascular injury.

  3. Intake of Mung Bean Protein Isolate Reduces Plasma Triglyceride Level in Rats

    Directory of Open Access Journals (Sweden)

    Nobuhiko Tachibana

    2013-09-01

    Full Text Available ABSTRACTBackground: Mung bean is well known as a starch source, but the physiological effects of mung bean protein have received little attention. In this study, we isolated mung bean protein from de-starched mung bean solutions, and investigated its influence on lipid metabolism. Objective: The aim of this study is to clarify the influence of the lipid metabolism by consumption of mung bean protein isolate (MPIMethods: Diets containing either mung bean protein isolate (MPI or casein were fed to normal rats for 28 days.Results: Both groups ate the same amount of food, but the plasma triglyceride level, relative liver weight and liver lipid contents (cholesterol and triglyceride pool in the MPI group were significantly lower than in the casein group. In the MPI group, the expression of sterol regulatory-element binding factor 1 (SREBF1 mRNA in the liver was significantly different when compared with the casein group. The significantly lower levels of insulin and free fatty acids in the MPI-fed rats may be due to the regulation of genes related to lipid metabolism in the liver.Conclusions: These results suggest that MPI may improve the plasma lipid profile by normalizing insulin sensitivity.Keywords: mung bean, Vigna radiata L., 8S globulin, triglyceride, β-conglycinin, 7S globulin, insulin sensitivity, SREBF1

  4. Diet-induced obesity reduces core body temperature across the estrous cycle and pregnancy in the rat.

    Science.gov (United States)

    Crew, Rachael C; Waddell, Brendan J; Maloney, Shane K; Mark, Peter J

    2018-04-16

    Obesity during pregnancy causes adverse maternal and fetal health outcomes and programs offspring for adult-onset diseases, including cardiovascular disease. Obesity also disrupts core body temperature (T c ) regulation in nonpregnant rodents; however, it is unknown whether obesity alters normal maternal T c adaptations to pregnancy. Since T c is influenced by the circadian system, and both obesity and pregnancy alter circadian biology, it was hypothesized that obesity disrupts the normal rhythmic patterns of T c before and during gestation. Obesity was induced by cafeteria (CAF) feeding in female Wistar rats for 8 weeks prior to and during gestation, whereas control (CON) animals had free access to chow. Intraperitoneal temperature loggers measured daily T c profiles throughout the study, while maternal body composition and leptin levels were assessed near term. Daily temperature profiles were examined for rhythmic features (mesor, amplitude and acrophase) by cosine regression analysis. CAF animals exhibited increased fat mass (93%) and associated hyperleptinemia (3.2-fold increase) compared to CON animals. CAF consumption reduced the average T c (by up to 0.29°C) across the estrous cycle and most of pregnancy; however, T c for CAF and CON animals converged toward the end of gestation. Obesity reduced the amplitude of T c rhythms at estrus and proestrus and on day 8 of pregnancy, but increased the amplitude at day 20 of pregnancy. Photoperiod analysis revealed that obesity reduced T c exclusively in the light period during pre-pregnancy but only during the dark period in late gestation. In conclusion, obesity alters rhythmic T c profiles and reduces the magnitude of the T c decline late in rat gestation, which may have implications for maternal health and fetal development.

  5. Sprague-Dawley rats display sex-linked differences in the pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA)

    International Nuclear Information System (INIS)

    Fonsart, Julien; Menet, Marie-Claude; Debray, Marcel; Hirt, Deborah; Noble, Florence; Scherrmann, Jean-Michel; Decleves, Xavier

    2009-01-01

    The use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has increased in recent years; it can lead to life-threatening hyperthermia and serotonin syndrome. Human and rodent males appear to be more sensitive to acute toxicity than are females. MDMA is metabolized to five main metabolites by the enzymes CYP1A2, CYP2D and COMT. Little is presently known about sex-dependent differences in the pharmacokinetics of MDMA and its metabolites. We therefore analyzed MDMA disposition in male and female rats by measuring the plasma and urine concentrations of MDMA and its metabolites using a validated LC-MS method. MDA AUC last and C max were 1.6- to 1.7-fold higher in males than in females given MDMA (5 mg/kg sc), while HMMA C max and AUC last were 3.2- and 3.5-fold higher, respectively. MDMA renal clearance was 1.26-fold higher in males, and that of MDA was 2.2-fold higher. MDMA AUC last and t 1/2 were 50% higher in females given MDMA (1 mg/kg iv). MDA C max and AUC last were 75-82% higher in males, with a 2.8-fold higher metabolic index. Finally, the AUC last of MDA was 0.73-fold lower in males given 1 mg/kg iv MDA. The volumes of distribution of MDMA and MDA at steady-state were similar in the two sexes. These data strongly suggest that differences in the N-demethylation of MDMA to MDA are major influences on the MDMA and MDA pharmacokinetics in male and female rats. Hence, males are exposed to significantly more toxic MDA, which could explain previously reported sexual dysmorphism in the acute effects and toxicity of MDMA in rats.

  6. Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

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    Ozkan Onal

    2015-01-01

    Full Text Available Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF intraperitoneally (ip for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD, catalase (CAT, glutathioneperoxidase (GSH-Px, malondyaldehide (MDA, and protein carbonyl (PCO were analyzed in tissue samples. Total oxidant status (TOS, and total antioxidant capacity (TAC were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy

  7. Dietary Supplementation with the Microalga Galdieria sulphuraria (Rhodophyta Reduces Prolonged Exercise-Induced Oxidative Stress in Rat Tissues

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    Simona Carfagna

    2015-01-01

    Full Text Available We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion.

  8. Dietary supplementation with the microalga Galdieria sulphuraria (Rhodophyta) reduces prolonged exercise-induced oxidative stress in rat tissues.

    Science.gov (United States)

    Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Pollio, Antonino; Venditti, Paola

    2015-01-01

    We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion.

  9. Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity

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    Kuniaki Tsutsumi

    2016-06-01

    Full Text Available Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7 and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect the anti-tumor activity of paclitaxel in cultured cell lines or tumor-bearing mice. These results suggest a clinical indication for polaprezinc in the prevention of paclitaxel-induced neuropathy.

  10. Augmenting digital displays with computation

    Science.gov (United States)

    Liu, Jing

    As we inevitably step deeper and deeper into a world connected via the Internet, more and more information will be exchanged digitally. Displays are the interface between digital information and each individual. Naturally, one fundamental goal of displays is to reproduce information as realistically as possible since humans still care a lot about what happens in the real world. Human eyes are the receiving end of such information exchange; therefore it is impossible to study displays without studying the human visual system. In fact, the design of displays is rather closely coupled with what human eyes are capable of perceiving. For example, we are less interested in building displays that emit light in the invisible spectrum. This dissertation explores how we can augment displays with computation, which takes both display hardware and the human visual system into consideration. Four novel projects on display technologies are included in this dissertation: First, we propose a software-based approach to driving multiview autostereoscopic displays. Our display algorithm can dynamically assign views to hardware display zones based on multiple observers' current head positions, substantially reducing crosstalk and stereo inversion. Second, we present a dense projector array that creates a seamless 3D viewing experience for multiple viewers. We smoothly interpolate the set of viewer heights and distances on a per-vertex basis across the arrays field of view, reducing image distortion, crosstalk, and artifacts from tracking errors. Third, we propose a method for high dynamic range display calibration that takes into account the variation of the chrominance error over luminance. We propose a data structure for enabling efficient representation and querying of the calibration function, which also allows user-guided balancing between memory consumption and the amount of computation. Fourth, we present user studies that demonstrate that the ˜ 60 Hz critical flicker fusion

  11. Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats

    Directory of Open Access Journals (Sweden)

    Miroslav Dinić

    2018-01-01

    Full Text Available The aim of this study was to test the potential of high molecular weight exopolysaccharide (EPS produced by the putative probiotic strain Lactobacillus paraplantarum BGCG11 (EPS CG11 to alleviate inflammatory pain in Wistar rats. The EPS CG11 was isolated from bacterial surface and was subjected to Fourier-transform infrared spectroscopy (FTIR and thermal analysis. FTIR spectra confirmed the polysaccharide structure of isolated sample, while the thermal methods revealed good thermal properties of the polymer. The antihyperalgesic and antiedematous effects of the EPS CG11 were examined in the rat model of inflammation induced by carrageenan injection in hind paw. The results showed that the intraperitoneal administration of EPS CG11 produced a significant decrease in pain sensations (mechanical hyperalgesia and a paw swelling in a dose-dependent manner as it was measured using Von Frey anesthesiometer and plethysmometer, respectively. These effects were followed by a decreased expression of IL-1β and iNOS mRNAs in rat’s paw tissue suggesting that the antihyperalgesic and antiedematous effects of the EPS CG11 are related to the suppression of inflammatory response. Additionally, we demonstrated that EPS CG11 exhibits immunosuppressive properties in the peritonitis model induced by carrageenan. Expression levels of pro-inflammatory mediators IL-1β, TNF-α and iNOS were decreased, together with the enhanced secretion of anti-inflammatory IL-10 and IL-6 cytokines, while neutrophil infiltration was not changed. To the best of our knowledge, this is the first study which reports an antihyperalgesic effect as the novel property of bacterial EPSs. Given the high demands of pharmaceutical industry for the replacement of commonly used analgesics due to numerous side effects, this study describes a promising natural compound for the future pharmacological testing in the area.

  12. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

    Directory of Open Access Journals (Sweden)

    Z.G. Zhao

    2014-02-01

    Full Text Available The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL on lipopolysaccharide (LPS-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1, myeloperoxidase (MPO, and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

  13. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

    International Nuclear Information System (INIS)

    Zhao, Z.G.; Zhang, L.L.; Niu, C.Y.; Zhang, J.

    2014-01-01

    The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na + -K + -ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na + -K + -ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na + -K + -ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis

  14. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Z.G.; Zhang, L.L.; Niu, C.Y.; Zhang, J. [Institute of Microcirculation, Hebei North University, Zhangjiakou, China, Institute of Microcirculation, Hebei North University, Zhangjiakou, Hebei (China)

    2014-02-17

    The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na{sup +}-K{sup +}-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na{sup +}-K{sup +}-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na{sup +}-K{sup +}-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

  15. Refreshing Refreshable Braille Displays.

    Science.gov (United States)

    Russomanno, Alexander; O'Modhrain, Sile; Gillespie, R Brent; Rodger, Matthew W M

    2015-01-01

    The increased access to books afforded to blind people via e-publishing has given them long-sought independence for both recreational and educational reading. In most cases, blind readers access materials using speech output. For some content such as highly technical texts, music, and graphics, speech is not an appropriate access modality as it does not promote deep understanding. Therefore blind braille readers often prefer electronic braille displays. But, these are prohibitively expensive. The search is on, therefore, for a low-cost refreshable display that would go beyond current technologies and deliver graphical content as well as text. And many solutions have been proposed, some of which reduce costs by restricting the number of characters that can be displayed, even down to a single braille cell. In this paper, we demonstrate that restricting tactile cues during braille reading leads to poorer performance in a letter recognition task. In particular, we show that lack of sliding contact between the fingertip and the braille reading surface results in more errors and that the number of errors increases as a function of presentation speed. These findings suggest that single cell displays which do not incorporate sliding contact are likely to be less effective for braille reading.

  16. EXPOSURE TO DIETHYL HEXYL PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN LONG EVANS HOODED AND SPRAGUE DAWLEY MALE RATS

    Science.gov (United States)

    DEHP is a plasticizer that alters sexual differentiation in the male rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels. When exposure includes the pubertal stage of life, DEHP and other phthalates delay puberty and reduce androgen-dependent tissue wei...

  17. Administration of structured lipid composed of MCT and fish oil reduces net protein catabolism in enterally fed burned rats.

    Science.gov (United States)

    Teo, T C; DeMichele, S J; Selleck, K M; Babayan, V K; Blackburn, G L; Bistrian, B R

    1989-01-01

    The effects of enteral feeding with safflower oil or a structured lipid (SL) derived from 60% medium-chain triglyceride (MCT) and 40% fish oil (MCT/fish oil) on protein and energy metabolism were compared in gastrostomy-fed burned rats (30% body surface area) by measuring oxygen consumption, carbon dioxide production, nitrogen balance, total liver protein, whole-body leucine kinetics, and rectus muscle and liver protein fractional synthetic rates (FSR, %/day). Male Sprague-Dawley rats (195 +/- 5g) received 50 ml/day of an enteral regimen containing 50 kcal, 2 g amino acids, and 40% nonprotein calories as lipid for three days. Protein kinetics were estimated by using a continuous L-[1-14C] leucine infusion technique on day 2. Thermally injured rats enterally fed MCT/fish oil yielded significantly higher daily and cumulative nitrogen balances (p less than or equal to 0.025) and rectus muscle (39%) FSR (p less than or equal to 0.05) when compared with safflower oil. MCT/fish oil showed a 22% decrease (p less than or equal to 0.005) in per cent flux oxidized and a 7% (p less than or equal to 0.05) decrease in total energy expenditure (TEE) versus safflower oil. A 15% increase in liver FSR was accompanied by a significant elevation (p less than or equal to 0.025) in total liver protein with MCT/fish oil. This novel SL shares the properties of other structured lipids in that it reduces the net protein catabolic effects of burn injury, in part, by influencing tissue protein synthetic rates. The reduction in TEE is unique to MCT/fish oil and may relate to the ability of fish oil to diminish the injury response. PMID:2500898

  18. Nopal feeding reduces adiposity, intestinal inflammation and shifts the cecal microbiota and metabolism in high-fat fed rats.

    Directory of Open Access Journals (Sweden)

    Sofia Moran-Ramos

    Full Text Available Nopal is a cactus plant widely consumed in Mexico that has been used in traditional medicine to aid in the treatment of type-2 diabetes. We previously showed that chronic consumption of dehydrated nopal ameliorated hepatic steatosis in obese (fa/fa rats; however, description of the effects on other tissues is sparse. The aim of the present study was to investigate the effects of nopal cladode consumption on intestinal physiology, microbial community structure, adipose tissue, and serum biochemistry in diet-induced obese rats. Rats were fed either a normal fat (NF diet or a HF diet containing 4% of dietary fiber from either nopal or cellulose for 6 weeks. Consumption of nopal counteracted HF-induced adiposity and adipocyte hypertrophy, and induced profound changes in intestinal physiology. Nopal consumption reduced biomarkers of intestinal inflammation (mRNA expression of IL-6 and oxidative stress (ROS, modfied gut microbiota composition, increasing microbial diversity and cecal fermentation (SCFA, and altered the serum metabolome. Interestingly, metabolomic analysis of dehydrated nopal revealed a high choline content, which appeared to generate high levels of serum betaine, that correlated negatively with hepatic triglyceride (TAG levels. A parallel decrease in some of the taxa associated with the production of trimethylamine, suggest an increase in choline absorption and bioavailability with transformation to betaine. The latter may partially explain the previously observed effect of nopal on the development of hepatic steatosis. In conclusion, this study provides new evidence on the effects of nopal consumption on normal and HF-diet induced changes in the intestine, the liver and systemic metabolism.

  19. Nopal feeding reduces adiposity, intestinal inflammation and shifts the cecal microbiota and metabolism in high-fat fed rats.

    Science.gov (United States)

    Moran-Ramos, Sofia; He, Xuan; Chin, Elizabeth L; Tovar, Armando R; Torres, Nimbe; Slupsky, Carolyn M; Raybould, Helen E

    2017-01-01

    Nopal is a cactus plant widely consumed in Mexico that has been used in traditional medicine to aid in the treatment of type-2 diabetes. We previously showed that chronic consumption of dehydrated nopal ameliorated hepatic steatosis in obese (fa/fa) rats; however, description of the effects on other tissues is sparse. The aim of the present study was to investigate the effects of nopal cladode consumption on intestinal physiology, microbial community structure, adipose tissue, and serum biochemistry in diet-induced obese rats. Rats were fed either a normal fat (NF) diet or a HF diet containing 4% of dietary fiber from either nopal or cellulose for 6 weeks. Consumption of nopal counteracted HF-induced adiposity and adipocyte hypertrophy, and induced profound changes in intestinal physiology. Nopal consumption reduced biomarkers of intestinal inflammation (mRNA expression of IL-6) and oxidative stress (ROS), modfied gut microbiota composition, increasing microbial diversity and cecal fermentation (SCFA), and altered the serum metabolome. Interestingly, metabolomic analysis of dehydrated nopal revealed a high choline content, which appeared to generate high levels of serum betaine, that correlated negatively with hepatic triglyceride (TAG) levels. A parallel decrease in some of the taxa associated with the production of trimethylamine, suggest an increase in choline absorption and bioavailability with transformation to betaine. The latter may partially explain the previously observed effect of nopal on the development of hepatic steatosis. In conclusion, this study provides new evidence on the effects of nopal consumption on normal and HF-diet induced changes in the intestine, the liver and systemic metabolism.

  20. Portulaca oleracea reduces triglyceridemia, cholesterolemia, and improves lecithin: cholesterol acyltransferase activity in rats fed enriched-cholesterol diet.

    Science.gov (United States)

    Zidan, Y; Bouderbala, S; Djellouli, F; Lacaille-Dubois, M A; Bouchenak, M

    2014-10-15

    The effects of Portulaca oleracea (Po) lyophilized aqueous extract were determined on the serum high-density lipoproteins (HDL2 and HDL3) amounts and composition, as well as on lecithin: cholesterol acyltansferase (LCAT) activity. Male Wistar rats (n = 12) were fed on 1% cholesterol-enriched diet for 10 days. After this phase, hypercholesterolemic rats (HC) were divided into two groups fed the same diet supplemented or not with Portulaca oleracea (Po-HC) (0.5%) for four weeks. Serum total cholesterol (TC) and triacylglycerols (TG), and liver TG values were respectively 1.6-, 1.8-, and 1.6-fold lower in Po-HC than in HC group. Cholesterol concentrations in LDL-HDL1, HDL2, and HDL3 were respectively 1.8, 1.4-, and 2.4-fold decreased in Po-HC group. HDL2 and HDL3 amounts, which were the sum of apolipoproteins (apos), TG, cholesteryl esters (CE), unesterified cholesterol (UC), and phospholipids (PL) contents, were respectively 4.5-fold higher and 1.2-fold lower with Po treatment. Indeed, enhanced LCAT activity (1.2-fold), its cofactor-activator apo A-I (2-fold) and its reaction product HDL2-CE (2.1-fold) were observed, whereas HDL3-PL (enzyme substrate) and HDL3-UC (acyl group acceptor) were 1.2- and 2.4-fold lower. Portulaca oleracea reduces triglyceridemia, cholesterolemia, and improves reverse cholesterol transport in rat fed enriched-cholesterol diet, contributing to anti-atherogenic effects. Copyright © 2014 Elsevier GmbH. All rights reserved.

  1. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    Directory of Open Access Journals (Sweden)

    Kuan Zhang

    Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  2. Garcinia mangostana Linn displays antidepressant-like and pro-cognitive effects in a genetic animal model of depression: a bio-behavioral study in the Flinders Sensitive Line rat.

    Science.gov (United States)

    Oberholzer, Inge; Möller, Marisa; Holland, Brendan; Dean, Olivia M; Berk, Michael; Harvey, Brian H

    2018-04-01

    There is abundant evidence for both disorganized redox balance and cognitive deficits in major depressive disorder (MDD). Garcinia mangostana Linn (GM) has anti-oxidant activity. We studied the antidepressant-like and pro-cognitive effects of raw GM rind in Flinders Sensitive Line (FSL) rats, a genetic model of depression, following acute and chronic treatment compared to a reference antidepressant, imipramine (IMI). The chemical composition of the GM extract was analysed for levels of α- and γ-mangostin. The acute dose-dependent effects of GM (50, 150 and 200 mg/kg po), IMI (20 mg/kg po) and vehicle were determined in the forced swim test (FST) in FSL rats, versus Flinders Resistant Line (FRL) control rats. Locomotor testing was conducted using the open field test (OFT). Using the most effective dose above coupled with behavioral testing in the FST and cognitive assessment in the novel object recognition test (nORT), a fixed dose 14-day treatment study of GM was performed and compared to IMI- (20 mg/kg/day) and vehicle-treated animals. Chronic treated animals were also assessed with respect to frontal cortex and hippocampal monoamine levels and accumulation of malondialdehyde. FSL rats showed significant cognitive deficits and depressive-like behavior, with disordered cortico-hippocampal 5-hydroxyindole acetic acid (5-HIAA) and noradrenaline (NA), as well as elevated hippocampal lipid peroxidation. Acute and chronic IMI treatment evoked pronounced antidepressant-like effects. Raw GM extract contained 117 mg/g and 11 mg/g α- and γ-mangostin, respectively, with acute GM demonstrating antidepressant-like effects at 50 mg/kg/day. Chronic GM (50 mg/kg/d) displayed significant antidepressant- and pro-cognitive effects, while demonstrating parity with IMI. Both behavioral and monoamine assessments suggest a more prominent serotonergic action for GM as opposed to a noradrenergic action for IMI, while both IMI and GM reversed hippocampal lipid peroxidation in

  3. Red algae (Gelidium amansii) reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide

    OpenAIRE

    Tsung-Han Yang; Hsien-Tsung Yao; Meng-Tsan Chiang

    2015-01-01

    Gelidium amansii (GA) is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1) rats without diabetes fed a high-fat diet (control group); (2) rats with diabetes fed a high-fat diet; (3) rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4) rats with...

  4. Synergistic Effects of Social Isolation and Morphine Addiction on Reduced Neurogenesis and BDNF Levels and the Resultant Deficits in Cognition and Emotional State in Male Rats.

    Science.gov (United States)

    Famitafreshi, Hamidreza; Karimian, Morteza; Fatima, Sulail

    2016-01-01

    Addiction to drugs of abuse is a devastating condition which results in deterioration of brain function. On the other hand, social isolation also produces cognitive deficits such as learning and memory impairment. This study was designed to evaluate the potential negative synergistic effects of social isolation and morphine addiction on brain functions. One hundred and two Sprague-Dawley rats were randomly divided into four groups for assessing neurogenesis and behaviour: group-housed, isolated, morphine-treated group-housed and morphine-treated isolated groups. Morphine- treated animals received BrdU (50 mg/kg; i.p.) and Morphine (0.75 mg/rat; i.p.) for 14 consecutive days, whereas, control rats received BrdU (50 mg/kg; i.p.) only. At the end of the study, Morris water maze and elevated plus maze tasks were performed to assess spatial working memory and anxiety levels, respectively. Furthermore, neurogenesis and BDNF levels were studied. Reference and working memory was markedly impaired in isolated and morphine-treated isolated rats as compared to group-housed rats and morphine-treated group-housed rats, respectively. Neurogenesis and BDNF levels were reduced in isolated and morphine-treated isolated rats as compared to group-housed rats and morphine-treated group-housed rats, respectively. Furthermore, rats in both isolated groups demonstrated low anxiety levels when compared to group housed groups. Isolation during addiction imparts devastating effects on brain. Thus, socialization of addicts can minimize addiction - induce cognitive deficits and improve neurogenesis.

  5. Longer treatment with alternative non-drug reinforcement fails to reduce resurgence of cocaine or alcohol seeking in rats.

    Science.gov (United States)

    Nall, Rusty W; Craig, Andrew R; Browning, Kaitlyn O; Shahan, Timothy A

    2018-04-02

    Provision of alternative non-drug reinforcement is among the most effective methods for treating substance use disorders. However, when alternative reinforcers become unavailable during treatment interruptions or upon cessation of treatment, relapse often occurs. Relapse following the loss of alternative reinforcement is known as resurgence. One factor that could reduce resurgence is longer duration of treatment with alternative reinforcement, but the available data are mixed. Further, the effects of length of treatment have previously only been examined with food seeking. The present experiments directly examined if duration of treatment impacted the magnitude of resurgence of cocaine or alcohol seeking in rats. First, rats were trained to self-administer cocaine (Experiment 1) or alcohol (Experiment 2) by performing a target behavior. Second, target behavior was extinguished and performing an alternative behavior produced an alternative non-drug (i.e., food) reinforcer. Finally, resurgence was assessed following removal of alternative reinforcement after either 5 or 20 sessions of treatment. Treatment duration did not differentially affect resurgence of cocaine seeking in Experiment 1 or Alcohol seeking in Experiment 2. These results suggest that extended treatment with alternative non-drug reinforcement may not decrease propensity to relapse. Further, these results may have implications for treatment of substance use disorders and for theories of resurgence. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Neuroimmunophilin GPI-1046 reduces ethanol consumption in part through activation of GLT1 in alcohol-preferring rats.

    Science.gov (United States)

    Sari, Y; Sreemantula, S N

    2012-12-27

    We have previously shown that ceftriaxone, β-lactam antibiotic known to upregulate glutamate transporter 1 (GLT1), reduced ethanol intake in alcohol-preferring (P) rats. GLT1 is a glial glutamate transporter that regulates the majority of extracellular glutamate uptake. We tested in this study the effects of neuroimmunophilin GPI-1046 (3-(3-pyridyl)-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate), known also to upregulate GLT1 expression, in ethanol intake in P rats. Male P rats had concurrent access to free choice of 15% and 30% ethanol, water, and food for five weeks. On Week 6, P rats continued in this drinking and food regimen and they were administered either 10 or 20mg/kg GPI-1046 (i.p.), or a vehicle for five consecutive days. Body weight, ethanol intake, and water consumption were measured daily for 8 days starting on Day 1 of GPI-1046 or vehicle i.p. injections. We have also tested the effect of GPI-1046 (20mg/kg) on daily sucrose (10%) intake. The data revealed significant dose-dependent effects in the reduction of ethanol intake starting 48 h after the first treatment with GPI-1046 throughout treatment and post-treatment periods. There were also dose-dependent increases in water intake. However, GPI-1046 treatment did not affect the body weight of all animals nor sucrose intake. Importantly, GPI-1046 (20mg/kg) increased GLT1 level compared to all groups in nucleus accumbens core (NAc-core). Alternatively, GPI-1046 (10mg/kg) upregulated GLT1 level in NAc-core compared to vehicle (ethanol naïve) group. Moreover, both doses of GPI-1046 increased significantly GLT1 level in the prefrontal cortex (PFC) compared to ethanol naïve vehicle group. GPI-1046 (20mg/kg) increased GLT1 level in PFC compared to naïve control group that was exposed to water and food only. These findings demonstrated that neuroimmunophilin GPI-1046 attenuates ethanol intake in part through the upregulation of GLT1 in PFC and NAc-core. Copyright © 2012 IBRO

  7. High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats

    Science.gov (United States)

    Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.

    2013-01-01

    Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (−9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

  8. Lycopene rich extract from red guava (Psidium guajava L.) displays anti-inflammatory and antioxidant profile by reducing suggestive hallmarks of acute inflammatory response in mice.

    Science.gov (United States)

    Vasconcelos, Andreanne G; Amorim, Adriany das G N; Dos Santos, Raimunda C; Souza, Jessica Maria T; de Souza, Luan Kelves M; Araújo, Thiago de S L; Nicolau, Lucas Antonio D; de Lima Carvalho, Lucas; de Aquino, Pedro Everson A; da Silva Martins, Conceição; Ropke, Cristina D; Soares, Pedro Marcos G; Kuckelhaus, Selma Aparecida S; Medeiros, Jand-Venes R; Leite, José Roberto de S A

    2017-09-01

    This study investigated the anti-inflammatory activity of the extract (LEG) and purified (LPG) lycopene from guava (Psidium guajava L.), as well as some mechanisms possibly involved in this effect. The anti-inflammatory activity was initially assessed using paw edema induced by Carrageenan, Dextran, Compound 48/80, Histamine and Prostaglandin E2 in Swiss mice. A peritonitis model was used to evaluate neutrophil migration, the activity of myeloperoxidase (MPO) and reduced glutathione (GSH) concentration; while the effect on the expression of iNOS, COX-2 and NF-κB, was assessed by immunohistochemistry analysis. Results showed that oral and intraperitoneal administration of LEG and LPG inhibited inflammation caused by carrageenan. LPG (12.5mg/kg p.o.) significantly inhibited the edema formation induced by different phlogistic agents and immunostaining for iNOS, COX-2 and NF-κB. Leukocytes migration in paw tissue and peritoneal cavity was reduced, as well as MPO concentration, whereas GSH levels increased. Thus, lycopene-rich extract from red guava has beneficial effect on acute inflammation, offering protection against the consequences of oxidative stress by downregulating inflammatory mediators and inhibiting gene expression involved in inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Reduced Plasmodium Parasite Burden Associates with CD38+ CD4+ T Cells Displaying Cytolytic Potential and Impaired IFN-γ Production

    Science.gov (United States)

    Burel, Julie G.; Apte, Simon H.; Groves, Penny L.; Klein, Kerenaftali; McCarthy, James S.; Doolan, Denise L.

    2016-01-01

    Using a unique resource of samples from a controlled human malaria infection (CHMI) study, we identified a novel population of CD4+ T cells whose frequency in the peripheral blood was inversely correlated with parasite burden following P. falciparum infection. These CD4+ T cells expressed the multifunctional ectoenzyme CD38 and had unique features that distinguished them from other CD4+ T cells. Specifically, their phenotype was associated with proliferation, activation and cytotoxic potential as well as significantly impaired production of IFN-γ and other cytokines and reduced basal levels of activated STAT1. A CD38+ CD4+ T cell population with similar features was identified in healthy uninfected individuals, at lower frequency. CD38+ CD4+ T cells could be generated in vitro from CD38- CD4+ T cells after antigenic or mitogenic stimulation. This is the first report of a population of CD38+ CD4+ T cells with a cytotoxic phenotype and markedly impaired IFN-γ capacity in humans. The expansion of this CD38+ CD4+ T population following infection and its significant association with reduced blood-stage parasite burden is consistent with an important functional role for these cells in protective immunity to malaria in humans. Their ubiquitous presence in humans suggests that they may have a broad role in host-pathogen defense. Trial Registration ClinicalTrials.gov clinical trial numbers ACTRN12612000814875, ACTRN12613000565741 and ACTRN12613001040752 PMID:27662621

  10. Histone deacetylase inhibition reduces hypothyroidism-induced neurodevelopmental defects in rats.

    Science.gov (United States)

    Kumar, Praveen; Mohan, Vishwa; Sinha, Rohit Anthony; Chagtoo, Megha; Godbole, Madan M

    2015-11-01

    Thyroid hormone (TH) through its receptor (TRα/β) influences spatio-temporal regulation of its target gene repertoire during brain development. Though hypothyroidism in WT rodent models of perinatal hypothyroidism severely impairs neurodevelopment, its effect on TRα/β knockout mice is less severe. An explanation to this paradox is attributed to a possible repressive action of unliganded TRs during development. Since unliganded TRs suppress gene expression through the recruitment of histone deacetylase (HDACs) via co-repressor complexes, we tested whether pharmacological inhibition of HDACs may prevent the effects of hypothyroidism on brain development. Using valproate, an HDAC inhibitor, we show that HDAC inhibition significantly blocks the deleterious effects of hypothyroidism on rat cerebellum, evident by recovery of TH target genes like Bdnf, Pcp2 and Mbp as well as improved dendritic structure of cerebellar Purkinje neurons. Together with this, HDAC inhibition also rescues hypothyroidism-induced motor and cognitive defects. This study therefore provides an insight into the role of HDACs in TH insufficiency during neurodevelopment and their inhibition as a possible therapeutics for treatment. © 2015 Society for Endocrinology.

  11. Ketoconazole-induced testicular damage in rats reduced by Gentiana extract.

    Science.gov (United States)

    Amin, Amr

    2008-04-01

    Ketoconazole (KET) is an antifungal drug with a broad spectrum of activity that also induces reproductive toxicity in humans and animals. The protective effect of Gentiana (GEN) extract (Gentiana lutea) against KET-induced testicular damage was evaluated in male Wistar rats. GEN extract was administered orally (1g/kgbwt/day) for 26 days. Three weeks after extract administration, KET was co-administered intraperitoneally at a dose of 100mg/kg once a day for 5 days. KET-induced reproductive toxicity was associated with clear reductions of the weights of testes and epididymides, sperm indices and serum testosterone levels. KET also induced severe testicular histopathological lesions such as degeneration of the seminiferous tubules and depletion of germ cells. In addition, marked oxidative damage to testicular lipids and alterations of natural antioxidants (catalase (CAT) and superoxide dismutase (SOD)) were reported in association with KET toxicity. Most of the KET-induced effects were greatly decreased with the concomitant application of GEN extract. This study suggests a protective role of GEN extract that could be attributed to its antioxidant properties.

  12. Decreased n-6/n-3 polyunsaturated fatty acid ratio reduces chronic reflux esophagitis in rats.

    Science.gov (United States)

    Wei, Jing-Jing; Tang, Du-Peng; Xie, Jing-Jing; Yang, Li-Yong; Zhuang, Ze-Hao

    2016-09-01

    To investigate the effect of dietary ratio of n-6/n-3 PUFAs on chronic reflux esophagitis (RE) and lipid peroxidation. Rat RE model were established and then fed on a diet contained different n-6/n-3 PUFA ratios (1:1.5, 5:1, 10:1) or received pure n-6 PUFA diet for 14 days. Esophageal pathological changes were evaluated using macroscopic examination and hematoxyline-eosin staining. IL-1β, IL-8, and TNFα mRNA and protein levels of were determined using RT-PCR and Western blotting, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined using ELISA. The severity of esophagitis was lowest in the PUFA(1:1.5) group (P<0.05). IL-1β, IL-8, and TNFα mRNA and protein and MDA levels were significantly increased in model groups with the increasing n-6/n-3 PUFA ratios. SOD levels were significantly decreased in all RE PUFA groups (P<0.05). Esophageal injury and lipid peroxidation appeared to be ameliorated by increased n-3 PUFAs intake. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Ivermectin reduces motor coordination, serum testosterone, and central neurotransmitter levels but does not affect sexual motivation in male rats.

    Science.gov (United States)

    Moreira, N; Sandini, T M; Reis-Silva, T M; Navas-Suáresz, P; Auada, A V V; Lebrun, I; Flório, J C; Bernardi, M M; Spinosa, H S

    2017-12-01

    Ivermectin (IVM) is a macrocyclic lactone used for the treatment of parasitic infections and widely used in veterinary medicine as endectocide. In mammals, evidence indicates that IVM interacts with γ-aminobutyric acid (GABA)-mediated chloride channels. GABAergic system is involved in the manifestation of sexual behavior. We previously found that IVM at therapeutic doses did not alter sexual behavior in male rats, but at a higher dose, the appetitive phase of sexual behavior was impaired. Thus, we investigated whether the reduction of sexual behavior that was previously observed was a consequence of motor or motivational deficits that are induced by IVM. Data showed significant decrease in striatal dopaminergic system activity and lower testosterone levels but no effects on sexual motivation or penile erection. These findings suggest IVM may activate the GABAergic system and reduce testosterone levels, resulting in a reduction of motor coordination as consequence of the inhibition of striatal dopamine release. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. An automated Y-maze based on a reduced instruction set computer (RISC) microcontroller for the assessment of continuous spontaneous alternation in rats.

    Science.gov (United States)

    Heredia-López, Francisco J; Álvarez-Cervera, Fernando J; Collí-Alfaro, José G; Bata-García, José L; Arankowsky-Sandoval, Gloria; Góngora-Alfaro, José L

    2016-12-01

    Continuous spontaneous alternation behavior (SAB) in a Y-maze is used for evaluating working memory in rodents. Here, the design of an automated Y-maze equipped with three infrared optocouplers per arm, and commanded by a reduced instruction set computer (RISC) microcontroller is described. The software was devised for recording only true entries and exits to the arms. Experimental settings are programmed via a keyboard with three buttons and a display. The sequence of arm entries and the time spent in each arm and the neutral zone (NZ) are saved as a text file in a non-volatile memory for later transfer to a USB flash memory. Data files are analyzed with a program developed under LabVIEW® environment, and the results are exported to an Excel® spreadsheet file. Variables measured are: latency to exit the starting arm, sequence and number of arm entries, number of alternations, alternation percentage, and cumulative times spent in each arm and NZ. The automated Y-maze accurately detected the SAB decrease produced in rats by the muscarinic antagonist trihexyphenidyl, and its reversal by caffeine, having 100 % concordance with the alternation percentages calculated by two trained observers who independently watched videos of the same experiments. Although the values of time spent in the arms and NZ measured by the automated system had small discrepancies with those calculated by the observers, Bland-Altman analysis showed 95 % concordance in three pairs of comparisons, while in one it was 90 %, indicating that this system is a reliable and inexpensive alternative for the study of continuous SAB in rodents.

  15. Calcium and α-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers123

    Science.gov (United States)

    Martin, Océane CB; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Audebert, Marc; Dupuy, Jacques; Meunier, Nathalie; Attaix, Didier; Vendeuvre, Jean-Luc; Mirvish, Sidney S; Kuhnle, Gunter CG; Cano, Noel; Corpet, Denis E

    2013-01-01

    Background: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats. Objectives: We investigated whether cured meat modulates biomarkers of cancer risk in human volunteers and whether specific agents can suppress cured meat–induced preneoplastic lesions in rats and associated biomarkers in rats and humans. Design: Six additives (calcium carbonate, inulin, rutin, carnosol, α-tocopherol, and trisodium pyrophosphate) were added to cured meat given to groups of rats for 14 d, and fecal biomarkers were measured. On the basis of these results, calcium and tocopherol were kept for the following additional experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d) and to human volunteers in a crossover study (180 g/d for 4 d). Rat colons were scored for mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats and volunteers. Results: Cured meat increased nitroso compounds and lipoperoxidation in human stools (both P meat (P = 0.01). Conclusion: Data suggest that the addition of calcium carbonate to the diet or α-tocopherol to cured meat may reduce colorectal cancer risk associated with cured-meat intake. This trial was registered at clinicaltrials.gov as NCT00994526. PMID:24025632

  16. Oxidative stress is reduced in Wistar rats exposed to smoke from tobacco and treated with specific broad-band pulse electromagnetic fields

    Directory of Open Access Journals (Sweden)

    Bajić V.

    2009-01-01

    Full Text Available There have been a number of attempts to reduce the oxidative radical burden of tobacco. A recently patented technology, pulse electromagnetic technology, has been shown to induce differential action of treated tobacco products versus untreated products on the production of reactive oxygen species (ROS in vivo. In a 90-day respiratory toxicity study, Wistar rats were exposed to cigarette smoke from processed and unprocessed tobacco and biomarkers of oxidative stress were compared with pathohistological analysis of rat lungs. Superoxide dismutase (SOD activity was decreased in a dose-dependent manner to 81% in rats exposed to smoke from normal cigarettes compared to rats exposed to treated smoke or the control group. These results correspond to pathohistological analysis of rat lungs, in which those rats exposed to untreated smoke developed initial signs of emphysema, while rats exposed to treated smoke showed no pathology, as in the control group. The promise of inducing an improved health status in humans exposed to smoke from treated cigarettes merits further investigation.

  17. Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl phthalate in male Long Evans rats.

    Directory of Open Access Journals (Sweden)

    Catherine A Smith

    Full Text Available Early developmental exposure to di(2-ethylhexyl phthalate (DEHP has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.

  18. Cyclophosphamide-induced cystitis reduces ASIC channel but enhances TRPV1 receptor function in rat bladder sensory neurons.

    Science.gov (United States)

    Dang, Khoa; Bielefeldt, Klaus; Gebhart, G F

    2013-07-01

    Using patch-clamp techniques, we studied the plasticity of acid-sensing ion channels (ASIC) and transient receptor potential V1 (TRPV1) channel function in dorsal root ganglia (DRG) neurons retrogradely labeled from the bladder. Saline (control) or cyclophosphamide (CYP) was given intraperitoneally on days 1, 3, and 5. On day 6, lumbosacral (LS, L6-S2) or thoracolumbar (TL, T13-L2) DRG were removed and dissociated. Bladders and bladder DRG neurons from CYP-treated rats showed signs of inflammation (greater myeloperoxidase activity; lower intramuscular wall pH) and increased size (whole cell capacitance), respectively, compared with controls. Most bladder neurons (>90%) responded to protons and capsaicin. Protons produced multiphasic currents with distinct kinetics, whereas capsaicin always triggered a sustained response. The TRPV1 receptor antagonist A-425619 abolished capsaicin-triggered currents and raised the threshold of heat-activated currents. Prolonged exposure to an acidic environment (pH range: 7.2 to 6.6) inhibited proton-evoked currents, potentiated the capsaicin-evoked current, and reduced the threshold of heat-activated currents in LS and TL bladder neurons. CYP treatment reduced density but not kinetics of all current components triggered by pH 5. In contrast, CYP-treatment was associated with an increased current density in response to capsaicin in LS and TL bladder neurons. Correspondingly, heat triggered current at a significantly lower temperature in bladder neurons from CYP-treated rats compared with controls. These results reveal that cystitis differentially affects TRPV1- and ASIC-mediated currents in both bladder sensory pathways. Acidification of the bladder wall during inflammation may contribute to changes in nociceptive transmission mediated through the TRPV1 receptor, suggesting a role for TRPV1 in hypersensitivity associated with cystitis.

  19. Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain.

    Science.gov (United States)

    Ragavendran, J Vaigunda; Laferrière, André; Xiao, Wen Hua; Bennett, Gary J; Padi, Satyanarayana S V; Zhang, Ji; Coderre, Terence J

    2013-01-01

    Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle, or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α(2)-adrenergic (α(2)A) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent antiallodynic effects in rats with chronic postischemia pain, and the antiallodynic dose-response curves of PDE and PA inhibitors were shifted 2.5- to 10-fold leftward when combined with nonanalgesic doses of α(2)A receptor agonists or NO donors. Topical combinations also produced significant antiallodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy, and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 hours after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α(2)A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain. This article presents the synergistic antiallodynic effects of combinations of α(2)A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest that effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected

  20. Lysine and arginine reduce the effects of cerebral ischemic insults and inhibit glutamate-induced neuronal activity in rats

    Directory of Open Access Journals (Sweden)

    Takashi Kondoh

    2010-06-01

    Full Text Available Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid, arginine, and their combination on ischemic insults (cerebral edema and infarction and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed two days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg, arginine (0.6 g/kg, or their combined administration (0.6 g/kg each. Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg, were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction, especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects.

  1. Soy isoflavone exposure through all life stages accelerates 17β-estradiol-induced mammary tumor onset and growth, yet reduces tumor burden, in ACI rats.

    Science.gov (United States)

    Möller, Frank Josef; Pemp, Daniela; Soukup, Sebastian T; Wende, Kathleen; Zhang, Xiajie; Zierau, Oliver; Muders, Michael H; Bosland, Maarten C; Kulling, Sabine E; Lehmann, Leane; Vollmer, Günter

    2016-08-01

    There is an ongoing debate whether the intake of soy-derived isoflavones (sISO) mediates beneficial or adverse effects with regard to breast cancer risk. Therefore, we investigated whether nutritional exposure to a sISO-enriched diet from conception until adulthood impacts on 17β-estradiol (E2)-induced carcinogenesis in the rat mammary gland (MG). August-Copenhagen-Irish (ACI) rats were exposed to dietary sISO from conception until postnatal day 285. Silastic tubes containing E2 were used to induce MG tumorigenesis. Body weight, food intake, and tumor growth were recorded weekly. At necropsy, the number, position, size, and weight of each tumor were determined. Plasma samples underwent sISO analysis, and the morphology of MG was analyzed. Tumor incidence and multiplicity were reduced by 20 and 56 %, respectively, in the sISO-exposed rats compared to the control rats. Time-to-tumor onset was shortened from 25 to 20 weeks, and larger tumors developed in the sISO-exposed rats. The histological phenotype of the MG tumors was independent of the sISO diet received, and it included both comedo and cribriform phenotypes. Morphological analyses of the whole-mounted MGs also showed no diet-dependent differences. Lifelong exposure to sISO reduced the overall incidence of MG carcinomas in ACI rats, although the time-to-tumor was significantly shortened.

  2. Water-soluble C60 fullerenes reduce manifestations of acute cholangitis in rats

    Science.gov (United States)

    Kuznietsova, H. M.; Lynchak, O. V.; Dziubenko, N. V.; Osetskyi, V. L.; Ogloblya, O. V.; Prylutskyy, Yu I.; Rybalchenko, V. K.; Ritter, U.; Scharff, P.

    2018-03-01

    Sclerosing cholangitis is the liver disease of uncertain etiology, extremely unfavorable prognosis and lack of effective medication therapy. Therefore, the effect of water-soluble biocompatible C60 fullerenes (C60FAS) on the liver functional state on rat acute-cholangitis model was aimed to be discovered. Acute cholangitis was simulated by single α-naphthyl isothiocyanate (ANIT, 100 mg/kg) per os administration; C60FAS (0.5 mg/kg) was administered either per os or intraperitoneally in 24 and 48 h after ANIT ingestion, and in 72 h the animals were sacrificed. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), the total and direct bilirubin, creatinine and urea in the blood serum were determined, and the liver morphological state was assessed. In animals experienced ANIT-induced acute cholangitis, the total and direct bilirubin, creatinine, ALT, AST, ALP and LDH 1.5-4-fold increase were observed, indicating cytolysis of hepatocytes, cholestasis, and renal dysfunction. The features of periductal fibrosis, biliary epithelium atrophy, and portal-portal linking septa formation were detected, confirming the sclerosing cholangitis development. C60FAS promoted to the normalization of direct and total bilirubin levels, the ALT activity and diminution of fibrotic features. In addition, C60FAS intraperitoneal administration also normalized the ALP activity, indicating the attenuation of disease symptoms. However, the AST activity and creatinine level remained unchanged, and the LDH activity even increased, manifesting the partial persistence of cholestasis and renal dysfunction. Thus, the therapeutic application of C60FAS promotes a partial protection of liver against cholangitis.

  3. Reduced Bone and Body Mass in Young Male Rats Exposed to Lead

    Directory of Open Access Journals (Sweden)

    Fellipe Augusto Tocchini de Figueiredo

    2014-01-01

    Full Text Available The aim of this study was to see whether there would be differences in whole blood versus tibia lead concentrations over time in growing rats prenatally. Lead was given in the drinking water at 30 mg/L from the time the dams were pregnant until offspring was 28- or 60-day-old. Concentrations of lead were measured in whole blood and in tibia after 28 (28D and 60 days (60D in control (C and in lead-exposed animals (Pb. Lead measurements were made by GF-AAS. There was no significant difference (P>0.05 in the concentration of whole blood lead between Pb-28D (8.0±1.1 μg/dL and Pb-60D (7.2±0.89 μg/dL, while both significantly varied (P<0.01 from controls (0.2 μg/dL. Bone lead concentrations significantly varied between the Pb-28D (8.02±1.12 μg/g and the Pb-60D (43.3±13.26 μg/g lead-exposed groups (P<0.01, while those exposed groups were also significantly higher (P<0.0001 than the 28D and 60D control groups (Pb < 1 μg/g. The Pb-60D group showed a 25% decrease in tibia mass as compared to the respective control. The five times higher amount of lead found in the bone of older animals (Pb-60D versus Pb-28D, which reinforces the importance of using bone lead as an exposure biomarker.

  4. Activation of Spinal α2-Adrenoceptors Using Diluted Bee Venom Stimulation Reduces Cold Allodynia in Neuropathic Pain Rats

    Directory of Open Access Journals (Sweden)

    Suk-Yun Kang

    2012-01-01

    Full Text Available Cold allodynia is an important distinctive feature of neuropathic pain. The present study examined whether single or repetitive treatment of diluted bee venom (DBV reduced cold allodynia in sciatic nerve chronic constriction injury (CCI rats and whether these effects were mediated by spinal adrenergic receptors. Single injection of DBV (0.25 or 2.5 mg/kg was performed into Zusanli acupoint 2 weeks post CCI, and repetitive DBV (0.25 mg/kg was injected for 2 weeks beginning on day 15 after CCI surgery. Single treatment of DBV at a low dose (0.25 mg/kg did not produce any anticold allodynic effect, while a high dose of DBV (2.5 mg/kg significantly reduced cold allodynia. Moreover, this effect of high-dose DBV was completely blocked by intrathecal pretreatment of idazoxan (α2-adrenoceptor antagonist, but not prazosin (α1-adrenoceptor antagonist or propranolol (nonselective β-adrenoceptor antagonist. In addition, coadministration of low-dose DBV (0.25 mg/kg and intrathecal clonidine (α2-adrenoceptor agonist synergically reduced cold allodynia. On the other hand, repetitive treatments of low-dose DBV showing no motor deficit remarkably suppressed cold allodynia from 7 days after DBV treatment. This effect was also reversed by intrathecal idazoxan injection. These findings demonstrated that single or repetitive stimulation of DBV could alleviate CCI-induced cold allodynia via activation of spinal α2-adrenoceptor.

  5. Linseed dietary fibers reduce apparent digestibility of energy and fat and weight gain in growing rats

    DEFF Research Database (Denmark)

    Kristensen, M.; Knudsen, K. E. B.; Jørgensen, H.

    2013-01-01

    Dietary fibers (DF) may affect energy balance, an effect often ascribed to the viscous nature of some water soluble DF, which affect luminal viscosity and thus multiple physiological processes. We have tested the hypothesis that viscous linseed DF reduce apparent nutrient digestibility, and limit...

  6. C57Bl/6 N mice on a western diet display reduced intestinal and hepatic cholesterol levels despite a plasma hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Desmarchelier Charles

    2012-03-01

    Full Text Available Abstract Background Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be determined. Methods We therefore measured cholesterol and phospholipid concentration in intestine and liver and quantified fecal neutral sterol and bile acid excretion in C57Bl/6 N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat Western diet containing 0.03% (w/w cholesterol. To identify the underlying mechanisms of dietary adaptations in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively. Results Mice on Western diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry. Conclusions Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load.

  7. Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats.

    Science.gov (United States)

    Haghnejad Azar, Adel; Oryan, Shahrbanoo; Bohlooli, Shahab; Panahpour, Hamdollah

    2017-01-01

    This study was conducted to examine the neuroprotective effects of α-tocopherol against edema formation and disruption of the blood-brain barrier (BBB) following transient focal cerebral ischemia in rats. Ninety-six male Sprague-Dawley rats were divided into 3 major groups (n = 32 in each), namely the sham, and control and α-tocopherol-treated (30 mg/kg) ischemic groups. Transient focal cerebral ischemia (90 min) was induced by occlusion of the left middle cerebral artery. At the end of the 24-hour reperfusion period, the animals were randomly selected and used for 4 investigations (n = 8) in each of the 3 main groups: (a) assessment of neurological score and measurement of infarct size, (b) detection of brain edema formation by the wet/dry method, (c) evaluation of BBB permeability using the Evans blue (EB) extravasation technique, and (d) assessment of the malondialdehyde (MDA) and reduced glutathione (GSH) concentrations using high-performance liquid chromatography methods. Induction of cerebral ischemia in the control group produced extensive brain edema (brain water content 83.8 ± 0.11%) and EB leakage into brain parenchyma (14.58 ± 1.29 µg/g) in conjunction with reduced GSH and elevated MDA levels (5.86 ± 0.31 mmol/mg and 63.57 ± 5.42 nmol/mg, respectively). Treatment with α-tocopherol significantly lowered brain edema formation and reduced EB leakage compared with the control group (p < 0.001, 80.1 ± 0.32% and 6.66 ± 0.87 µg/g, respectively). Meanwhile, treatment with α-tocopherol retained tissue GSH levels and led to a lower MDA level (p < 0.01, 10.17 ± 0.83 mmol/mg, and p < 0.001, 26.84 ± 4.79 nmol/mg, respectively). Treatment with α-tocopherol reduced ischemic edema formation and produced protective effects on BBB function following ischemic stroke occurrence. This effect could be through increasing antioxidant activity. © 2016 S. Karger AG, Basel.

  8. Erythroxylum pungens elicits vasorelaxation by reducing intracellular calcium concentration in vascular smooth muscle cells of rats

    Directory of Open Access Journals (Sweden)

    Aurylene C. Oliveira

    2012-01-01

    Full Text Available The cardiovascular effects elicited by the ethanolic extract obtained from the roots of Erythroxylum pungens O.E. Schulz, Erythroxylaceae (EEEP and the vasorelaxant effect induced by its main tropane alkaloid (pungencine were investigated. In normotensive rats, administration of EEEP (1, 10, 30 and 60 mg/kg i.v., randomly produced dose-dependent hypotension (-2±1, -7±0.5 -17.6±1, -24±1 Δ mmHg, n=5 followed by tachycardia (3±0.5, 7±2, 7.1±1, 10±5 Δ bpm, n=5. In intact phenylephrine (Phe, 10 µM-pre-contracted rings, EEEP (0.01-500 µg/mL induced concentration-dependent vasorelaxation (EC50 13.7±5.5 µg/mL, Maximal Response= 92±2.6%, and this effect was unchanged after the removal of the vascular endothelium (EC50 27.2±4.7 µg/ml, Maximal Response= 88.3±3.3 %. In KCl (80 mM-pre-contracted-endothelium-denuded rings, EEEP elicited concentration-dependent relaxation (EC50= 128.2±11.2 µg/mL, Maximal Response 76.8±3.4%. Vasorelaxation has also been achieved with tonic contractions evoked by the L-type Ca2+ channel agonist Bay K 8644 (EC50 80.2±9.1 µg/mL, Maximal Response 86.3±8.3%. In addition, in a depolarizing medium, EEEP inhibited CaCl2 (30-500 µg/mL induced contractions and caused a concentration-dependent rightward shift of the relaxation curves. Lastly, the tropane alkaloid pungencine caused vasorelaxation in mesenteric arteries resembling to the EEEP responses. These results suggests that EEEP induces hypotension and vasorelaxation, at least in part, due to the reduction in [Ca2+]i in vascular smooth muscle cells.

  9. Reduced pulmonary blood flow in regions of injury 2 hours after acid aspiration in rats.

    Science.gov (United States)

    Richter, Torsten; Bergmann, Ralf; Musch, Guido; Pietzsch, Jens; Koch, Thea

    2015-01-01

    Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following acid aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after acid aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after acid instillation by measuring the concentration of [(68)Ga]-radiolabeled microspheres using positron emission tomography. CT scans revealed increased lung density in areas of acid aspiration. Lung injury was accompanied by impaired gas exchange. Acid aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes (P < 0.001). The PBF ratio of the middle region of the injured versus uninjured lungs of the aspiration group (0.86 [0.7;0.9], median [25%;75%]) was significantly lower than the PBF ratio in the left versus right lung of the control group (1.02 [1.0;1.05]; P = 0.016). The PBF pattern 2 hours after aspiration-induced lung injury showed a redistribution of PBF away from injured regions that was likely responsible for the partial recovery from hypoxemia over time. Treatments given intravenously 2 hours after acid-induced lung injury may not preferentially reach the injured lung regions, contrary to what occurs during the first hour of inflammation. Please see related article: http://dx.doi.org/10.1186/s12871-015-0014-z.

  10. EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters

    DEFF Research Database (Denmark)

    Axelstad Petersen, Marta; Hass, Ulla; Scholze, M.

    2018-01-01

    and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10 months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes...... of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant......Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we...

  11. The mechano-gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in rats with ligated femoral arteries.

    Science.gov (United States)

    Copp, Steven W; Kim, Joyce S; Ruiz-Velasco, Victor; Kaufman, Marc P

    2016-05-01

    Mechanical and metabolic stimuli arising from contracting muscles evoke the exercise pressor reflex. This reflex is greater in a rat model of simulated peripheral arterial disease in which a femoral artery is chronically ligated than it is in rats with freely perfused femoral arteries. The role played by the mechanically sensitive component of the exaggerated exercise pressor reflex in ligated rats is unknown. We tested the hypothesis that the mechano-gated channel inhibitor GsMTx4, a relatively selective inhibitor of mechano-gated Piezo channels, reduces the exercise pressor reflex in decerebrate rats with ligated femoral arteries. Injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the pressor response to Achilles tendon stretch (a purely mechanical stimulus) but had no effect on the pressor responses to intra-arterial injection of α,β-methylene ATP or lactic acid (purely metabolic stimuli). Moreover, injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced both the integrated pressor area (control 535 ± 21, GsMTx4 218 ± 24 mmHg·s; P reflex contributes to the exaggerated exercise pressor reflex during intermittent hindlimb muscle contractions in rats with ligated femoral arteries. Copyright © 2016 the American Physiological Society.

  12. Green tea, phytic acid, and inositol in combination reduced the incidence of azoxymethane-induced colon tumors in Fisher 344 male rats.

    Science.gov (United States)

    Khatiwada, Janak; Verghese, Martha; Davis, Shurrita; Williams, Leonard L

    2011-11-01

    Experimental as well as epidemiologic studies in human populations provide evidence that consumption of phytochemicals reduces the incidence of degenerative diseases. Green tea (GT) catechins are known for their antioxidative potential. Phytic acid (PA) also acts as a natural antioxidant and may have numerous health benefits. This experiment was designed to investigate the inhibitory effects of combinations of 1% and 2% GT, PA, and inositol (I) in reducing the incidence of azoxymethane-induced colon tumors in Fisher 344 male rats. After an acclimatization period of 1 week, nine groups of rats (15 rats per group) were initially assigned to consume AIN 93 G diet and later AIN 93 M diet after 20 weeks of age. Treatments were given in drinking water. All rats received azoxymethane injections (16 mg/kg of body weight) subcutaneously at 7 and 8 weeks of age. Rats were killed at 45 weeks of age by CO(2) euthanasia. Tumor incidence (93.76%) and the number of tumors per tumor-bearing rat ratio (2.25) were significantly (P<.05) higher in the control group compared with treatment groups. Glutathione S-transferase activity was significantly (P<.05) higher in rats fed combinations of 2% GT+PA+I and GT+PA (33.25 ± 1.23 and 29.83 ± 1.10 μmol/mL, respectively) compared with other groups. These findings suggest that the synergistic effect of the 2% level of GT, PA, and I may reduce the incidence of colon tumors and therefore have potential as a chemopreventive agent.

  13. Simvastatin and Dipentyl Phthalate Display Different Mechanisms of Action but Exhibit Dose Additive Effects on Fetal Testicular Testosterone Production in Sprague Dawley Rats

    Science.gov (United States)

    Sex differentiation of the male reproductive tract in mammals is driven, in part, by fetal androgen production. In utero exposure to some phthalate esters (PEs) alters fetal Leydig cell differentiation, reducing the expression of several genes associated with steroid synthesis/tr...

  14. Intragastric nutrient infusion reduces motivation for food in male and female rats.

    Science.gov (United States)

    Maske, Calyn B; Loney, Gregory C; Lilly, Nicole; Terrill, Sarah J; Williams, Diana L

    2018-03-13

    The idea that gut-derived satiation signals influence food reward has recently gained traction, but this hypothesis is largely based on studies focused on neural circuitry, not the peripherally released signals. Here, we directly tested the hypothesis that intragastric (IG) nutrient infusion can suppress motivation for food. In a series of experiments, IG sucrose infusion (15 kcal) significantly and reliably reduced operant responding for a sucrose reward on a progressive ratio (PR) schedule. Moreover, food deprivation for 24 h before the test session did not prevent the suppressive effect of nutrients. The suppressive effect of IG sucrose on fixed ratio 5 (FR5) operant responding was also assessed as a comparison. The effect of IG nutrients to reduce motivation was not limited to sucrose; IG Ensure infusion (9.3 kcal) also significantly reduced PR operant responding for sucrose pellets. To verify that these effects are not secondary to the osmotic challenge of concentrated nutrients, we tested IG infusion of non-caloric saline solutions equiosmolar to 40% sucrose or Ensure, and found no effect. Finally, we focused on glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK) as candidate mediators for the effect of IG nutrients. Pretreatment with Exendin-9, a GLP-1R antagonist, delivered IP, significantly attenuated the ability of IG nutrients to suppress PR responding and breakpoint in males, but not females, whereas pretreatment with Devazepide, a CCKA receptor antagonist, failed to do so in both sexes. Together, these data support the idea that nutrient-induced satiation signals influence food reward, and may implicate GLP-1 in this process.

  15. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  16. The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

    International Nuclear Information System (INIS)

    Schultz, M.K.; Wright, L.K.M.; Stone, M.F.; Schwartz, J.E.; Kelley, N.R.; Moffett, M.C.; Lee, R.B.; Lumley, L.A.

    2012-01-01

    Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA A ) receptors. However, seizure activity itself causes the endocytosis of GABA A receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD 50 ; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY) was examined as an

  17. The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, M.K.; Wright, L.K.M.; Stone, M.F.; Schwartz, J.E.; Kelley, N.R.; Moffett, M.C.; Lee, R.B.; Lumley, L.A., E-mail: lucille.a.lange@us.army.mil

    2012-03-15

    Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA{sub A}) receptors. However, seizure activity itself causes the endocytosis of GABA{sub A} receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD{sub 50}; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY) was

  18. Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain

    Directory of Open Access Journals (Sweden)

    Rachel D. Moloney

    2015-01-01

    Full Text Available Glutamate, the main excitatory neurotransmitter in the central nervous system, exerts its effect through ionotropic and metabotropic receptors. Of these, group III mGlu receptors (mGlu 4, 6, 7, 8 are among the least studied due to a lack of pharmacological tools. mGlu7 receptors, the most highly conserved isoform, are abundantly distributed in the brain, especially in regions, such as the amygdala, known to be crucial for the emotional processing of painful stimuli. Visceral hypersensitivity is a poorly understood phenomenon manifesting as an increased sensitivity to visceral stimuli. Glutamate has long been associated with somatic pain processing leading us to postulate that crossover may exist between these two modalities. Moreover, stress has been shown to exacerbate visceral pain. ADX71743 is a novel, centrally penetrant, negative allosteric modulator of mGlu7 receptors. Thus, we used this tool to explore the possible involvement of this receptor in the mediation of visceral pain in a stress-sensitive model of visceral hypersensitivity, namely the Wistar Kyoto (WKY rat. ADX71743 reduced visceral hypersensitivity in the WKY rat as exhibited by increased visceral sensitivity threshold with concomitant reductions in total number of pain behaviours. Moreover, AD71743 increased total distance and distance travelled in the inner zone of the open field. These findings show, for what is to our knowledge, the first time, that mGlu7 receptor signalling plays a role in visceral pain processing. Thus, negative modulation of the mGlu7 receptor may be a plausible target for the amelioration of stress-induced visceral pain where there is a large unmet medical need.

  19. Valproic acid reduces insulin-resistance, fat deposition and FOXO1-mediated gluconeogenesis in type-2 diabetic rat.

    Science.gov (United States)

    Khan, Sabbir; Kumar, Sandeep; Jena, Gopabandhu

    2016-06-01

    Recent evidences highlighted the role of histone deacetylases (HDACs) in insulin-resistance, gluconeogenesis and islet function. HDACs can modulate the expression of various genes, which directly or indirectly affect glucose metabolism. This study was aimed to evaluate the role of valproic acid (VPA) on fat deposition, insulin-resistance and gluconeogenesis in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet and low dose streptozotocin. VPA at the doses of 150 and 300 mg/kg/day and metformin (positive control) 150 mg/kg twice daily for 10 weeks were administered by oral gavage. Insulin-resistance, dyslipidemia and glycemia were evaluated by biochemical estimations, while fat accumulation and structural alteration were assessed by histopathology. Protein expression and insulin signaling were evaluated by western blot and immunohistochemistry. VPA treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, fat deposition in brown adipose tissue, white adipose tissue and liver, which are comparable to metformin treatment. Further, VPA inhibited the gluconeogenesis and glucagon expression as well as restored the histopathological alterations in pancreas and liver. Our findings provide new insights on the anti-diabetic role of VPA in type-2 diabetes mellitus by the modulation of insulin signaling and forkhead box protein O1 (FOXO1)-mediated gluconeogenesis. Since VPA is a well established clinical drug, the detailed molecular mechanisms of the present findings can be further investigated for possible clinical use. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  20. Developmental Vitamin D (DVD) Deficiency Reduces Nurr1 and TH Expression in Post-mitotic Dopamine Neurons in Rat Mesencephalon.

    Science.gov (United States)

    Luan, Wei; Hammond, Luke Alexander; Cotter, Edmund; Osborne, Geoffrey William; Alexander, Suzanne Adele; Nink, Virginia; Cui, Xiaoying; Eyles, Darryl Walter

    2018-03-01

    Developmental vitamin D (DVD) deficiency has been proposed as an important risk factor for schizophrenia. Our previous study using Sprague Dawley rats found that DVD deficiency disrupted the ontogeny of mesencephalic dopamine neurons by decreasing the mRNA level of a crucial differentiation factor of dopamine cells, the nuclear receptor related 1 protein (Nurr1). However, it remains unknown whether this reflects a reduction in dopamine cell number or in Nurr1 expression. It is also unclear if any particular subset of developing dopamine neurons in the mesencephalon is selectively affected. In this study, we employed state-of-the-art spinning disk confocal microscopy optimized for the imaging of tissue sections and 3D segmentation to assess post-mitotic dopamine cells on a single-cell basis in the rat mesencephalon at embryonic day 15. Our results showed that DVD deficiency did not alter the number, morphology, or positioning of post-mitotic dopamine cells. However, the ratio of Nurr1+TH+ cells in the substantia nigra pars compacta (SNc) compared with the ventral tegmental area (VTA) was increased in DVD-deficient embryos. In addition, the expression of Nurr1 in immature dopamine cells and mature dopamine neurons in the VTA was decreased in DVD-deficient group. Tyrosine hydroxylase was selectively reduced in SNc of DVD-deficient mesencephalon. We conclude that DVD deficiency induced early alterations in mesencephalic dopamine development may in part explain the abnormal dopamine-related behaviors found in this model. Our findings may have broader implications for how certain environmental risk factors for schizophrenia may shape the ontogeny of dopaminergic systems and by inference increase the risk of schizophrenia.

  1. Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model.

    Science.gov (United States)

    Dai, Bingyang; Li, Lan; Li, Qiangqiang; Song, Xiaoxiao; Chen, Dongyang; Dai, Jin; Yao, Yao; Yan, Wenjin; Teng, Huajian; Yang, Fang; Xu, Zhihong; Jiang, Qing

    2017-07-01

    : L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel-Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis.

  2. Running Reduces Uncontrollable Stress-Evoked Serotonin and Potentiates Stress-Evoked Dopamine Concentrations in the Rat Dorsal Striatum.

    Directory of Open Access Journals (Sweden)

    Peter J Clark

    Full Text Available Accumulating evidence from both the human and animal literature indicates that exercise reduces the negative consequences of stress. The neurobiological etiology for this stress protection, however, is not completely understood. Our lab reported that voluntary wheel running protects rats from expressing depression-like instrumental learning deficits on the shuttle box escape task after exposure to unpredictable and inescapable tail shocks (uncontrollable stress. Impaired escape behavior is a result of stress-sensitized serotonin (5-HT neuron activity in the dorsal raphe (DRN and subsequent excessive release of 5-HT into the dorsal striatum following exposure to a comparatively mild stressor. However, the possible mechanisms by which exercise prevents stress-induced escape deficits are not well characterized. The purpose of this experiment was to test the hypothesis that exercise blunts the stress-evoked release of 5-HT in the dorsal striatum. Changes to dopamine (DA levels were also examined, since striatal DA signaling is critical for instrumental learning and can be influenced by changes to 5-HT activity. Adult male F344 rats, housed with or without running wheels for 6 weeks, were either exposed to tail shock or remained undisturbed in laboratory cages. Twenty-four hours later, microdialysis was performed in the medial (DMS and lateral (DLS dorsal striatum to collect extracellular 5-HT and DA before, during, and following 2 mild foot shocks. We report wheel running prevents foot shock-induced elevation of extracellular 5-HT and potentiates DA concentrations in both the DMS and DLS approximately 24 h following exposure to uncontrollable stress. These data may provide a possible mechanism by which exercise prevents depression-like instrumental learning deficits following exposure to acute stress.

  3. Acanthopanax divaricatus var. chiisanensis reduces blood pressure via the endothelial nitric oxide synthase pathway in the spontaneously hypertensive rat model.

    Science.gov (United States)

    Park, Soo-Yeon; Do, Gyeong-Min; Lee, Sena; Lim, Yeni; Shin, Jae-Ho; Kwon, Oran

    2014-09-01

    In this study, we investigated the antihypertensive effects of Acanthopanax divaricatus var. chiisanensis extract (AE) and its active compound, acanthoside D (AD), on arterial blood pressure (BP) in vivo and endothelial function in vitro. We hypothesized that AE has antihypertensive effects, which is attributed to enhancement of endothelial function via the improvement of nitric oxide synthesis or the angiotensin II (Ang II) response. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) were randomly divided into 7 groups and then fed the following diets for 14 weeks: WKY fed a normal diet (WN); SHR fed a normal diet (SN); SHR fed a high-cholesterol (HC) diet (SH); SHR fed a HC diet with AE of 150, 300, 600 mg/kg body weight (SH-L, SH-M, SH-H); and SHR fed an HC diet with AD of 600 μg/kg body weight (SH-D). Blood pressure was significantly reduced in the SH-H compared with the SH from week 10 until week 14; BP was also significantly decreased in the SHR fed a HC diet with AE of 300 at week 14. Aortic wall thickness showed a tendency to decrease by AE and AD treatment. The SH-H showed increased endothelial nitric oxide synthase (eNOS) expression in the intima and media, compared with the SH. Furthermore, a significant increase in intracellular nitric oxide production was induced by AE and AD treatment in human umbilical vein endothelial cells. A significant increase of phospho-eNOS was found with a high dose of AE in human umbilical vein endothelial cells but not with AD. These results suggest that AE can regulate BP and improve endothelial function via eNOS-dependent vasodilation. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction.

    Science.gov (United States)

    Côté, Isabelle; Green, Sara M; Morgan, Drake; Carter, Christy S; Tümer, Nihal; Scarpace, Philip J

    2018-03-01

    Recent evidence indicate that melanotan II (MTII) reduces body mass independently of caloric reduction. Because MTII induces a transient hypophagia, caloric reduction is still considered a primary mechanism for MTII-mediated body mass loss. To examine the contribution of caloric reduction to long-term body mass loss in response to MTII, we centrally infused MTII or vehicle in ad libitum fed (MTII and Control) animals in comparison with a group of animals that were pair-fed (PF) to the MTII group. Food intake and body mass were recorded daily, and body composition was assessed biweekly. The present study demonstrates that central MTII-mediated body mass loss is only partially mediated by caloric restriction, and the long-term body mass loss is independent of the initial hypophagia. More importantly, central MTII administration induced a rapid but sustained fat mass loss, independently of caloric reduction. MTII-treated animals preserved their lean/fat mass ratio throughout the study, whereas PF animals underwent a transient reduction of lean/fat mass ratio that was only normalized when food intake returned to Control level. In summary, it can be concluded that activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction.

  5. Coexistence of reduced function of natural killer cells and osteoclasts in two distinct osteopetrotic mutations in the rat

    International Nuclear Information System (INIS)

    Popoff, S.N.; Jackson, M.E.; Koevary, S.B.; Marks, S.C. Jr.

    1991-01-01

    Recent evidence suggesting that immune cells and their products (cytokines) play an important role in the regulation of skeletal development and function, particularly of the osteoclast, implies that immune cell dysfunction may be involved in the pathogenesis of certain skeletal disorders. The mammalian osteopetroses are a pathogenetically heterogeneous group of skeletal disorders characterized by skeletal sclerosis resulting from reduced osteoclast-mediated bone resorption. Using a 51 Cr release microcytotoxicity assay we demonstrated that splenic natural killer (NK) cell activity was significantly reduced in two distinctly different osteopetrotic mutations in the rat, osteopetrosis (op) and toothless (tl). To determine whether this reduction in NK cell-mediated cytotoxicity is caused by decreased cell number and/or function in these osteopetrotic mutants, we quantitated NK cells by analyzing mononuclear cell suspensions labeled for two-color fluorescence with OX8 and OX19 monoclonal antibodies in a fluorescence-activated cell sorter. Flow cytometry of these double-labeled cells revealed that the percentage of NK cells (OX8+/OX19- subset) in op and tl spleens was not significantly different from that of normal spleens. These results suggest that NK cells in these osteopetrotic mutants are functionally defective. Thus aberrations in osteoclast and NK cell function coexist in these mutations, and their developmental relationships deserve further study

  6. Intramuscular Neurotrophin-3 normalizes low threshold spinal reflexes, reduces spasms and improves mobility after bilateral corticospinal tract injury in rats.

    Science.gov (United States)

    Kathe, Claudia; Hutson, Thomas Haynes; McMahon, Stephen Brendan; Moon, Lawrence David Falcon

    2016-10-19

    Brain and spinal injury reduce mobility and often impair sensorimotor processing in the spinal cord leading to spasticity. Here, we establish that complete transection of corticospinal pathways in the pyramids impairs locomotion and leads to increased spasms and excessive mono- and polysynaptic low threshold spinal reflexes in rats. Treatment of affected forelimb muscles with an adeno-associated viral vector (AAV) encoding human Neurotrophin-3 at a clinically-feasible time-point after injury reduced spasticity. Neurotrophin-3 normalized the short latency Hoffmann reflex to a treated hand muscle as well as low threshold polysynaptic spinal reflexes involving afferents from other treated muscles. Neurotrophin-3 also enhanced locomotor recovery. Furthermore, the balance of inhibitory and excitatory boutons in the spinal cord and the level of an ion co-transporter in motor neuron membranes required for normal reflexes were normalized. Our findings pave the way for Neurotrophin-3 as a therapy that treats the underlying causes of spasticity and not only its symptoms.

  7. Extract of grapefruit-seed reduces acute pancreatitis induced by ischemia/reperfusion in rats: possible implication of tissue antioxidants.

    Science.gov (United States)

    Dembinski, A; Warzecha, Z; Konturek, S J; Ceranowicz, P; Dembinski, M; Pawlik, W W; Kusnierz-Cabala, B; Naskalski, J W

    2004-12-01

    Grapefruit seed extract (GSE) has been shown to exert antibacterial, antifungal and antioxidant activity possibly due to the presence of naringenin, the flavonoid with cytoprotective action on the gastric mucosa. No study so far has been undertaken to determine whether this GSE is also capable of preventing acute pancreatic damage induced by ischemia/reperfusion (I/R), which is known to result from reduction of anti-oxidative capability of pancreatic tissue, and whether its possible preventive effect involves an antioxidative action of this biocomponent. In this study carried out on rats with acute hemorrhagic pancreatitis induced by 30 min partial pancreatic ischemia followed by 6 h of reperfusion, the GSE or vehicle (vegetable glycerin) was applied intragastrically in gradually increasing amounts (50-500 microl) 30 min before I/R. Pretreatment with GSE decreased the extent of pancreatitis with maximal protective effect of GSE at the dose 250 microl. GSE reduced the pancreatitis-evoked increase in serum lipase and poly-C specific ribonuclease activity, and attenuated the marked fall in pancreatic blood flow and pancreatic DNA synthesis. GSE administered alone increased significantly pancreatic tissue content of lipid peroxidation products, malondialdehyde and 4-hydroxyalkens, and when administered before I/R, GSE reduced the pancreatitis-induced lipid peroxidation. We conclude that GSE exerts protective activity against I/R-induced pancreatitis probably due to the activation of antioxidative mechanisms in the pancreas and the improvement of pancreatic blood flow.

  8. Antenatal hypoxia induces programming of reduced arterial blood pressure response in female rat offspring: role of ovarian function.

    Directory of Open Access Journals (Sweden)

    DaLiao Xiao

    Full Text Available In utero exposure to adverse environmental factors increases the risk of cardiovascular disease in adulthood. The present study tested the hypothesis that antenatal hypoxia causes a gender-dependent programming of altered arterial blood pressure response (BP in adult offspring. Time-dated pregnant rats were divided into normoxic and hypoxic (10.5% O2 from days 15 to 21 of gestation groups. The experiments were conducted in adult offspring. Antenatal hypoxia caused intrauterine growth restriction, and resulted in a gender-dependent increase Angiotensin II (Ang II-induced BP response in male offspring, but significant decrease in BP response in female offspring. The baroreflex sensitivity was not significantly altered. Consistent with the reduced blood pressure response, antenatal hypoxia significantly decreased Ang II-induced arterial vasoconstriction in female offspring. Ovariectomy had no significant effect in control animals, but significantly increased Ang II-induced maximal BP response in prenatally hypoxic animals and eliminated the difference of BP response between the two groups. Estrogen replacement in ovariectomized animals significantly decreased the BP response to angiotensin II I only in control, but not in hypoxic animals. The result suggests complex programming mechanisms of antenatal hypoxia in regulation of ovary function. Hypoxia-mediated ovary dysfunction results in the phenotype of reduced vascular contractility and BP response in female adult offspring.

  9. Maternal-fetal hepatic and placental metabolome profiles are associated with reduced fetal growth in a rat model of maternal obesity

    DEFF Research Database (Denmark)

    Mumme, Karen; Gray, Clint; Reynolds, Clare M.

    2016-01-01

    : Metabolomic profiling was used to reveal altered maternal and fetal metabolic pathways in a model of diet induced obesity during pregnancy, leading to reduced fetal growth. Methods: We examined the metabolome of maternal and fetal livers, and placenta following a high fat and salt intake. Sprague–Dawley rats...

  10. Potentiation of mGlu5 receptors with the novel enhancer, VU0360172, reduces spontaneous absence seizures in WAG/Rij rats

    NARCIS (Netherlands)

    D'Amore, V.; Santolini, I.; Rijn, C.M. van; Biagioni, F.; Molinaro, G.; Prete, A.; Conn, P.J.; Lindsley, C.W.; Zhou, Y.; Vinson, P.N.; Rodriguez, A.L.; Jones, C.K.; Stauffer, S.R.; Nicoletti, F.; Luijtelaar, E.L.J.M. van; Ngomba, R.T.

    2013-01-01

    Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat

  11. Diltiazem Reduces Mortality and Breakdown of ATP in Red Blood Cell Induced by Isoproterenol in a Freely Moving Rat Model in Vivo

    Directory of Open Access Journals (Sweden)

    Pollen K.F. Yeung

    2014-09-01

    Full Text Available The benefit of calcium channel blockers for cardiovascular prevention against heart attack and stroke has not been firmly supported. We investigated the possible cardiovascular protective effect of diltiazem (DTZ against injury induced by isoproterenol using a freely moving rat model in vivo. Sprague Dawley rats were injected subcutaneously (sc with either 5 or 10 mg/kg of DTZ, or saline as control, twice daily for five doses. One hour after the last injection, a single dose of isoproterenol (30 mg/kg was injected sc to each rat. Blood samples were collected serially for 6 h for measurement of adenine nucleotides (ATP, ADP and AMP in red blood cell (RBC by a validated HPLC. The study has shown isoproterenol induced 50% mortality and also increased RBC concentrations of AMP from 0.04 ± 0.02 to 0.29 ± 0.21 mM at the end of the experiment (p < 0.05. Treatment with 10 mg/kg of DTZ reduced mortality from 50% to <20% and attenuated the increase of RBC concentrations of AMP from +0.25 ± 0.22 in the control rats to +0.072 ± 0.092 mM (p < 0.05. The study concluded that 10 mg/kg of DTZ reduced mortality and breakdown of ATP induced by isoproterenol in rats.

  12. Glucose acutely reduces cytosolic and mitochondrial H2O2 in rat pancreatic beta-cells.

    Science.gov (United States)

    Deglasse, Jean-Philippe; Roma, Leticia Prates; Pastor-Flores, Daniel; Gilon, Patrick; Dick, Tobias P; Jonas, Jean-Christophe

    2018-05-14

    Whether H2O2 contributes to the glucose-dependent stimulation of insulin secretion by pancreatic β-cells is highly controversial. We used two H2O2-sensitive probes, roGFP2-Orp1 and HyPer with its pH-control SypHer, to test the acute effects of glucose, monomethylsuccinate, leucine with glutamine, and α-ketoisocaproate, on β-cell cytosolic and mitochondrial H2O2 concentrations. We then tested the effects of low H2O2 and menadione concentrations on insulin secretion. RoGFP2-Orp1 was more sensitive than HyPer to H2O2 (response at 2-5 vs. 10µM) and less pH-sensitive. Under control conditions, stimulation with glucose reduced mitochondrial roGFP2-Orp1 oxidation without affecting cytosolic roGFP2-Orp1 and HyPer fluorescence ratios, except for the pH-dependent effects on HyPer. However, stimulation with glucose decreased the oxidation of both cytosolic probes by 15µM exogenous H2O2. The glucose effects were not affected by overexpression of catalase, mitochondrial catalase or superoxide dismutase 1 and 2. They followed the increase in NAD(P)H autofluorescence, were maximal at 5mM glucose in the cytosol and 10mM glucose in the mitochondria, and were partly mimicked by the other nutrients. Exogenous H2O2 (1-15µM) did not affect insulin secretion. By contrast, menadione (1-5µM) did not increase basal insulin secretion but reduced the stimulation of insulin secretion by 20mM glucose. Subcellular changes in β-cell H2O2 levels are better monitored with roGFP2-Orp1 than HyPer/SypHer. Nutrients acutely lower mitochondrial H2O2 levels in β-cells and promote degradation of exogenously supplied H2O2 in both cytosolic and mitochondrial compartments. The glucose-dependent stimulation of insulin secretion occurs independently of a detectable increase in β-cell cytosolic or mitochondrial H2O2 levels.

  13. Reduced Utilization of Selenium by Naked Mole Rats Due to a Specific Defect in GPx1 Expression*

    Science.gov (United States)

    Kasaikina, Marina V.; Lobanov, Alexei V.; Malinouski, Mikalai Y.; Lee, Byung Cheon; Seravalli, Javier; Fomenko, Dmitri E.; Turanov, Anton A.; Finney, Lydia; Vogt, Stefan; Park, Thomas J.; Miller, Richard A.; Hatfield, Dolph L.; Gladyshev, Vadim N.

    2011-01-01

    Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase activities were similar in mice and MR. However, glutathione peroxidase activity was an order of magnitude lower in MR liver and kidney than in mouse tissues. In addition, metabolic labeling of MR cells with 75Se revealed a loss of the abundant glutathione peroxidase 1 (GPx1) band, whereas other selenoproteins were preserved. To characterize the MR selenoproteome, we sequenced its liver transcriptome. Gene reconstruction revealed standard selenoprotein sequences except for GPx1, which had an early stop codon, and SelP, which had low selenocysteine content. When expressed in HEK 293 cells, MR GPx1 was present in low levels, and its expression could be rescued neither by removing the early stop codon nor by replacing its SECIS element. In addition, GPx1 mRNA was present in lower levels in MR liver than in mouse liver. To determine if GPx1 deficiency could account for the reduced selenium content, we analyzed GPx1 knock-out mice and found reduced selenium levels in their livers and kidneys. Thus, MR is characterized by the reduced utilization of selenium due to a specific defect in GPx1 expression. PMID:21372135

  14. A history of alternative reinforcement reduces stimulus generalization of ethanol-seeking in a rat recovery model

    Science.gov (United States)

    Ginsburg, Brett C.; Lamb, R. J.

    2012-01-01

    BACKGROUND Longer periods of recovery reduce the likelihood of relapse, which may be due to a reduced ability of various stimuli to occasion alcohol or drug seeking. However, this hypothesis remains largely uninvestigated. METHODS Here we assessed the ability of intermediate stimuli to occasion responding for ethanol in rats trained to discriminate an 8kHz tone signaling a food fixed-ratio (FR) of 5 and an ethanol FR5, from a 16kHz tone signaling a food FR150 and ethanol FR5. In the presence of the 8kHz tone responding for food predominates, and in the presence of the 16 kHz tone, responding for ethanol predominates. RESULTS In the context of alternation between these conditions, varying the tone from 8 to 16kHz produces a graded increase in ethanol (versus food) responding, consistent with a stimulus generalization function. A recent history of responding under food-predominant choice conditions, either during the test session or in the four sessions that precede it shifts the generalization function downwards. Extending this history to nine sessions shifts the curve further downwards. The stimulus generalization function was similar in a separate group, trained with different relative ratios for food and ethanol, but with similar behavioral allocation under each discriminative stimulus. Finally, withholding access to food and ethanol for 4 or 16 sessions did not affect the stimulus generalization gradient. CONCLUSION These results suggest that longer histories of reinforced alternative behavior might reduce the likelihood of relapse by decreasing the control exerted over alcohol- or drug-seeking by stimuli similar to those that previously occasioned alcohol- or drug-seeking. PMID:23122598

  15. Palmitoylethanolamide treatment reduces blood pressure in spontaneously hypertensive rats: involvement of cytochrome p450-derived eicosanoids and renin angiotensin system.

    Directory of Open Access Journals (Sweden)

    Giuseppina Mattace Raso

    Full Text Available Palmitoylethanolamide (PEA, a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR. Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF, and renin angiotensin system (RAS modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the

  16. A novel herbal treatment reduces depressive-like behaviors and increases brain-derived neurotrophic factor levels in the brain of type 2 diabetic rats

    Directory of Open Access Journals (Sweden)

    Luo C

    2016-11-01

    Full Text Available Chun Luo,1,* Yuting Ke,1,* Yanyan Yuan,1 Ming Zhao,1 Fuyan Wang,1 Yisheng Zhang,2 Shizhong Bu1 1Runliang Diabetes Laboratory, Diabetes Research Center, Ningbo University, 2Department of Gynaecology and Obstetrics, Ningbo Medical Center, Li Huili Eastern Hospital, Ningbo, Zhejiang, People’s Republic of China *These authors contributed equally to this work Background: Radix Puerariae and hawthorn fruit have been demonstrated to treat diabetes. They offer potential benefits for preventing depression in diabetes. Objective: The aim of this study was to investigate whether the combination of Radix Puerariae and hawthorn fruit (CRPHF could prevent depression in a diabetic rat model generated by feeding the rats with a high-fat diet and a low-dose streptozotocin (STZ. Methods: The CRPHF was provided by the Shanghai Chinese Traditional Medical University. Twenty-four rats were randomly divided into four groups: normal control, normal-given-CRPHF (NC, diabetic control, and diabetic-given-CRPHF (DC groups. The type 2 diabetic model was created by feeding the rats with a high-fat diet for 4 weeks followed by injection of 25 mg/kg STZ. CRPHF was given at 2 g/kg/d to the rats of NC and DC groups by intragastric gavage daily for 4 weeks after the type 2 diabetic model was successfully created. Body weight, random blood glucose (RBG, oral glucose tolerance test, total cholesterol (TC, triglyceride (TG, high-density lipoprotein cholesterol (HDL-C, and low-density lipoprotein cholesterol (LDL-C were measured during the study. Depressive-like behavior was evaluated at the end of the treatment by using the open field test (OFT, the elevated plus-maze test (EPMT, locomotor activity test (LAT, and forced swimming test (FST. Levels of extracellular signal-regulated protein kinase (ERK and brain-derived neurotrophic factor (BDNF in the prefrontal cortex were evaluated by using Western blot. Results: 1 CRPHF reduced RBG and improved glucose tolerance in diabetic rats

  17. Mutagenicity of the potent rat hepatocarcinogen 6BT to the liver of transgenic (lacI) rats: consideration of a reduced mutation assay protocol.

    Science.gov (United States)

    Lefevre, P A; Tinwell, H; Ashby, J

    1997-01-01

    6-(p-dimethylaminophenylazo)benzothiazole (6BT) is an unusually potent rat hepatocarcinogen, producing large malignant liver tumours after only 2-3 months of dietary administration in a riboflavin-deficient diet. This azocarcinogen has been evaluated in a Big Blue F344 transgenic rat (lacI) gene mutation assay. In a reproduction of the early stages of the carcinogenesis bioassay of this agent, rats were maintained on a riboflavin-deficient diet and were given 10 consecutive daily doses of 6BT (10 mg/kg) by oral gavage. The animals were killed and the livers examined 11 days after the final dose. The livers of 6BT-treated rats showed evidence of hepatocellular hypertrophy in centrolobular areas, with some indication of an increased incidence of mitotic figures. An approximately 10-fold increase in the mutation frequency of DNA isolated from an aliquot of the combined liver homogenates of 6BT-treated rats was observed over that obtained from an equivalent aliquot from control animals. Examination of DNA samples isolated from the livers of individual animals confirmed that 6BT was mutagenic in Big Blue rat livers. These data extend the sensitivity of this transgenic assay to include azo hepatocarcinogens. The determination of mutation frequencies using pooled tissue samples represented a major resource-saving adaptation of the assay protocol in the present study; the general advantages and disadvantages of this practice are discussed.

  18. Invisible Display in Aluminum

    DEFF Research Database (Denmark)

    Prichystal, Jan Phuklin; Hansen, Hans Nørgaard; Bladt, Henrik Henriksen

    2005-01-01

    Bang & Olufsen a/s has been working with ideas for invisible integration of displays in metal surfaces. Invisible integration of information displays traditionally has been possible by placing displays behind transparent or semitransparent materials such as plastic or glass. The wish for an integ......Bang & Olufsen a/s has been working with ideas for invisible integration of displays in metal surfaces. Invisible integration of information displays traditionally has been possible by placing displays behind transparent or semitransparent materials such as plastic or glass. The wish...... for an integrated display in a metal surface is often ruled by design and functionality of a product. The integration of displays in metal surfaces requires metal removal in order to clear the area of the display to some extent. The idea behind an invisible display in Aluminum concerns the processing of a metal...

  19. Phototherapy with blue and green mixed-light is as effective against unconjugated jaundice as blue light and reduces oxidative stress in the Gunn rat model.

    Science.gov (United States)

    Uchida, Yumiko; Morimoto, Yukihiro; Uchiike, Takao; Kamamoto, Tomoyuki; Hayashi, Tamaki; Arai, Ikuyo; Nishikubo, Toshiya; Takahashi, Yukihiro

    2015-07-01

    Phototherapy using blue light-emitting diodes (LED) is effective against neonatal jaundice. However, green light phototherapy also reduces unconjugated jaundice. We aimed to determine whether mixed blue and green light can relieve jaundice with minimal oxidative stress as effectively as either blue or green light alone in a rat model. Gunn rats were exposed to phototherapy with blue (420-520 nm), filtered blue (FB; 440-520 nm without 1.00), respectively. Blue plus green phototherapy is as effective as blue phototherapy and it attenuates irradiation-induced oxidative stress. Combined blue and green spectra might be effective against neonatal hyperbilirubinemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. The free radical spin-trap alpha-PBN attenuates periinfarct depolarizations following permanent middle cerebral artery occlusion in rats without reducing infarct volume

    DEFF Research Database (Denmark)

    Christensen, Thomas; Bruhn, Torben; Diemer, Nils Henrik

    2003-01-01

    The effect of the free radical spin-trap alpha-phenyl-butyl-tert-nitrone (alpha-PBN) in permanent focal cerebral ischemia in rats was examined in two series of experiments. In the first, rats were subjected to permanent occlusion of the middle cerebral artery (MCAO) and treated 1 h after occlusion...... with a single dose of alpha-PBN (100 mg/kg) or saline. Body temperature was measured and controlled for the first 24 h to obtain identical temperature curves in the two groups. Cortical infarct volumes were determined on histological sections 7 days later. alpha-PBN did not significantly reduce infarct volume...

  1. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir

    2013-01-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during...... the perinatal period. Pregnant Wistar rats were administered a 200mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND...

  2. Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

    Science.gov (United States)

    Oh, Da Hee; Kim, Jung Yeon; Lee, Bong Gn; You, Jeong Soon; Chang, Kyung Ja; Chung, Hyunju; Yoo, Myung Chul; Yang, Hyung-In; Kang, Ja-Heon; Hwang, Yoo Chul; Ahn, Kue Jeong; Chung, Ho-Yeon

    2012-01-01

    This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve β-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients. PMID:23114424

  3. Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis.

    Science.gov (United States)

    Tellier, Liane E; Treviño, Elda A; Brimeyer, Alexandra L; Reece, David S; Willett, Nick J; Guldberg, Robert E; Temenoff, Johnna S

    2018-05-01

    As a potential treatment for osteoarthritis (OA), we have developed injectable and hydrolytically degradable heparin-based biomaterials with tunable sulfation for the intra-articular delivery of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a protein known to inhibit plasmin which may degrade extracellular matrix within OA joints. We first assessed the effect of heparin sulfation on TSG-6 anti-plasmin activity and found that while fully sulfated (Hep) and heparin desulfated at only the N position (Hep-N) significantly enhanced TSG-6 bioactivity in vitro, fully desulfated heparin (Hep-) had no effect, indicating that heparin sulfation plays a significant role in modulating TSG-6 bioactivity. Next, TSG-6 loaded, degradable 10 wt% Hep-N microparticles (MPs) were delivered via intra-articular injection into the knee at 1, 7, and 15 days following medial meniscal transection (MMT) injury in a rat model. After 21 days, cartilage thickness, volume, and attenuation were significantly increased with soluble TSG-6, indicating degenerative changes. In contrast, no significant differences were observed with TSG-6 loaded MP treatment, demonstrating that TSG-6 loaded MPs reduced cartilage damage following MMT injury. Ultimately, our results indicate that Hep-N can enhance TSG-6 anti-plasmin activity and that Hep-N-based biomaterials may be an effective method for TSG-6 delivery to treat OA.

  4. Glutamate reduces glucose utilization while concomitantly enhancing AQP9 and MCT2 expression in cultured rat hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Fabio eTescarollo

    2014-08-01

    Full Text Available The excitatory neurotransmitter glutamate has been reported to have a major impact on brain energy metabolism. Using primary cultures of rat hippocampal neurons, we observed that glutamate reduces glucose utilization in this cell type, suggesting alteration in mitochondrial oxidative metabolism. The aquaglyceroporin AQP9 and the monocarboxylate transporter MCT2, two transporters for oxidative energy substrates, appear to be present in mitochondria of these neurons. Moreover, they not only co-localize but they interact with each other as they were found to co-immunoprecipitate from hippocampal neuron homogenates. Exposure of cultured hippocampal neurons to glutamate 100 µM for 1 hour led to enhanced expression of both AQP9 and MCT2 at the protein level without any significant change at the mRNA level. In parallel, a similar increase in the protein expression of LDHA was evidenced without an effect on the mRNA level. These data suggest that glutamate exerts an influence on neuronal energy metabolism likely through a regulation of the expression of some key mitochondrial proteins.

  5. Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

    Science.gov (United States)

    Hanlon, Lauren A.; Huh, Jimmy W.

    2016-01-01

    Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

  6. Combined sub-threshold dosages of phenobarbital and low-frequency stimulation effectively reduce seizures in amygdala-kindled rats.

    Science.gov (United States)

    Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi, Homeira; Mirnajafi-Zadeh, Javad

    2014-08-01

    Low-frequency stimulation (LFS) is a potential therapy utilized in patients who do not achieve satisfactory control of seizures with pharmacological treatments. Here, we investigated the interaction between anticonvulsant effects of LFS and phenobarbital (a commonly used medicine) on amygdala-kindled seizures in rats. Animals were kindled by electrical stimulation of basolateral amygdala in a rapid manner (12 stimulations/day). Fully kindled animals randomly received one of the three treatment choices: phenobarbital (1, 2, 3, 4 and 8 mg/kg; i.p.; 30 min before kindling stimulation), LFS (one or 4 packages contained 100 or 200 monophasic square wave pulses, 0.1-ms pulse duration at 1 Hz, immediately before kindling stimulation) or a combination of both (phenobarbital at 3 mg/kg and LFS). Phenobarbital alone at the doses of 1, 2 and 3 mg/kg had no significant effect on the main seizure parameters. LFS application always produced anticonvulsant effects unless applied with the pattern of one package of 100 pulses, which is considered as non-effective. All the seizure parameters were significantly reduced when phenobarbital (3 mg/kg) was administered prior to the application of the non-effective pattern of LFS. Phenobarbital (3 mg/kg) also increased the anticonvulsant actions of the effective LFS pattern. Our results provide an evidence of a positive cumulative anticonvulsant effect of LFS and phenobarbital, suggesting a potential combination therapy at sub-threshold dosages of phenobarbital and LFS to achieve a satisfactory clinical effect.

  7. Reduced glutathione concentration and glutathione reductase activity in various rat tissues after the administration of some radioprotective agents

    International Nuclear Information System (INIS)

    Pulpanova, J.; Kovarova, H.; Ledvina, M.

    1982-01-01

    The concentrations of reduced glutathione (GSH) and activity of glutathione reductase were investigated in rat liver, kidney and spleen after intraperitoneal administration of cystamine (50 mg/kg), mexamine (10 mg/kg), or a mixture of cystamine with mexamine (20 + 10 mg/kg). The GSH concentration increased after the administration of cystamine in the liver (maximum between the 20th and 30th min), in the kidney and spleen (maximum after 60 min). The cystamine + mexamine mixture also caused a significant increase of the GSH concentration in all the organs investigated; however, the values increased at earlier intervals as after the cystamine administration. No substantial effect was shown in the case of the mexamine administration, only 30 min after the administration the values were higher. The activity of glutathione reductase was significantly lower over the entire period examined. This was found in the liver and kidney as after the administration of cystamine, as after the radioprotective mixture. There was also a less pronounced inhibition of the enzyme activity in the spleen. Mexamine as a single radioprotector had practically no influence on the activity. (author)

  8. Promotion of colon cancer metastases in rat liver by fish oil diet is not due to reduced stroma formation

    NARCIS (Netherlands)

    Klieverik, L.; Fehres, O.; Griffini, P.; van Noorden, C. J.; Frederiks, W. M.

    2001-01-01

    Recently, it was demonstrated that dietary omega-3 polyunsaturated fatty acids (PUFAs) induce 10-fold more metastases in number and 1000-fold in volume in an animal model of colon cancer metastasis in rat liver. It was observed that tumors of rats on a fish oil diet lacked peritumoral stroma unlike

  9. Long-term melatonin treatment reduces ovarian mass and enhances tissue antioxidant defenses during ovulation in the rat

    Directory of Open Access Journals (Sweden)

    L.G.A. Chuffa

    2011-03-01

    Full Text Available Melatonin regulates the reproductive cycle, energy metabolism and may also act as a potential antioxidant indoleamine. The present study was undertaken to investigate whether long-term melatonin treatment can induce reproductive alterations and if it can protect ovarian tissue against lipid peroxidation during ovulation. Twenty-four adult female Wistar rats, 60 days old (± 250-260 g, were randomly divided into two equal groups. The control group received 0.3 mL 0.9% NaCl + 0.04 mL 95% ethanol as vehicle, and the melatonin-treated group received vehicle + melatonin (100 µg·100 g body weight-1·day-1 both intraperitoneally daily for 60 days. All animals were killed by decapitation during the morning estrus at 4:00 am. Body weight gain and body mass index were reduced by melatonin after 10 days of treatment (P < 0.05. Also, a marked loss of appetite was observed with a fall in food intake, energy intake (melatonin 51.41 ± 1.28 vs control 57.35 ± 1.34 kcal/day and glucose levels (melatonin 80.3 ± 4.49 vs control 103.5 ± 5.47 mg/dL towards the end of treatment. Melatonin itself and changes in energy balance promoted reductions in ovarian mass (20.2% and estrous cycle remained extensive (26.7%, arresting at diestrus. Regarding the oxidative profile, lipid hydroperoxide levels decreased after melatonin treatment (6.9% and total antioxidant substances were enhanced within the ovaries (23.9%. Additionally, melatonin increased superoxide dismutase (21.3%, catalase (23.6% and glutathione-reductase (14.8% activities and the reducing power (10.2% GSH/GSSG ratio. We suggest that melatonin alters ovarian mass and estrous cyclicity and protects the ovaries by increasing superoxide dismutase, catalase and glutathione-reductase activities.

  10. The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

    Science.gov (United States)

    Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa

    2015-05-01

    Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats

    Directory of Open Access Journals (Sweden)

    I. Stefanon

    2009-10-01

    Full Text Available Myocardial infarction leads to compensatory ventricular remodeling. Disturbances in myocardial contractility depend on the active transport of Ca2+ and Na+, which are regulated by Na+-K+ ATPase. Inappropriate regulation of Na+-K+ ATPase activity leads to excessive loss of K+ and gain of Na+ by the cell. We determined the participation of Na+-K+ ATPase in ventricular performance early and late after myocardial infarction. Wistar rats (8-10 per group underwent left coronary artery ligation (infarcted, Inf or sham-operation (Sham. Ventricular performance was measured at 3 and 30 days after surgery using the Langendorff technique. Left ventricular systolic pressure was obtained under different ventricular diastolic pressures and increased extracellular Ca2+ concentrations (Ca2+e and after low and high ouabain concentrations. The baseline coronary perfusion pressure increased 3 days after myocardial infarction and normalized by 30 days (Sham 3 = 88 ± 6; Inf 3 = 130 ± 9; Inf 30 = 92 ± 7 mmHg; P < 0.05. The inotropic response to Ca2+e and ouabain was reduced at 3 and 30 days after myocardial infarction (Ca2+ = 1.25 mM; Sham 3 = 70 ± 3; Inf 3 = 45 ± 2; Inf 30 = 29 ± 3 mmHg; P < 0.05, while the Frank-Starling mechanism was preserved. At 3 and 30 days after myocardial infarction, ventricular Na+-K+ ATPase activity and contractility were reduced. This Na+-K+ ATPase hypoactivity may modify the Na+, K+ and Ca2+ transport across the sarcolemma resulting in ventricular dysfunction.

  12. Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model.

    Science.gov (United States)

    Rigo, Federica; De Stefano, Nicola; Navarro-Tableros, Victor; David, Ezio; Rizza, Giorgia; Catalano, Giorgia; Gilbo, Nicholas; Maione, Francesca; Gonella, Federica; Roggio, Dorotea; Martini, Silvia; Patrono, Damiano; Salizzoni, Mauro; Camussi, Giovanni; Romagnoli, Renato

    2018-05-01

    The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution. Livers were perfused for 4 hours without (control group, n = 10) or with HLSC-EV (treated group, n = 9). Bile production was quantified; perfusate samples were collected hourly to measure metabolic (pH, pO2, pCO2) and cytolysis parameters (AST, alanine aminotransferase, lactate dehydrogenase). At the end of perfusion, we assessed HLSC-EV engraftment by immunofluorescence, tissue injury by histology, apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, tissue hypoxia-inducible factor 1-α, and transforming growth factor-beta 1 RNA expression by quantitative reverse transcription-polymerase chain reaction. During hypoxic NMP, livers were able to maintain homeostasis and produce bile. In the treated group, AST (P = 0.018) and lactate dehydrogenase (P = 0.032) levels were significantly lower than those of the control group at 3 hours of perfusion, and AST levels persisted lower at 4 hours (P = 0.003). By the end of NMP, HLSC-EV had been uptaken by hepatocytes, and EV treatment significantly reduced histological damage (P = 0.030), apoptosis (P = 0.049), and RNA overexpression of hypoxia-inducible factor 1-α (P < 0.0001) and transforming growth factor-beta 1 (P = 0.014). HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.

  13. Targeting Germinal Matrix Hemorrhage-Induced Overexpression of Sodium-Coupled Bicarbonate Exchanger Reduces Posthemorrhagic Hydrocephalus Formation in Neonatal Rats.

    Science.gov (United States)

    Li, Qian; Ding, Yan; Krafft, Paul; Wan, Weifeng; Yan, Feng; Wu, Guangyong; Zhang, Yixin; Zhan, Qunling; Zhang, John H

    2018-01-31

    Germinal matrix hemorrhage (GMH) is a leading cause of mortality and lifelong morbidity in preterm infants. Posthemorrhagic hydrocephalus (PHH) is a common complication of GMH. A sodium-coupled bicarbonate exchanger (NCBE) encoded by solute carrier family 4 member 10 gene is expressed on the choroid plexus basolateral membrane and may play a role in cerebrospinal fluid production and the development of PHH. Following GMH, iron degraded from hemoglobin has been linked to PHH. Choroid plexus epithelial cells also contain iron-responsive element-binding proteins (IRPs), IRP1, and IRP2 that bind to mRNA iron-responsive elements. The present study aims to resolve the following issues: (1) whether the expression of NCBE is regulated by IRPs; (2) whether NCBE regulates the formation of GMH-induced hydrocephalus; and (3) whether inhibition of NCBE reduces PHH development. GMH model was established in P7 rat pups by injecting bacterial collagenase into the right ganglionic eminence. Another group received iron trichloride injections instead of collagenase. Deferoxamine was administered intraperitoneally for 3 consecutive days after GMH/iron trichloride. Solute carrier family 4 member 10 small interfering RNA or scrambled small interfering RNA was administered by intracerebroventricular injection 24 hours before GMH and followed with an injection every 7 days over 21 days. NCBE expression increased while IRP2 expression decreased after GMH/iron trichloride. Deferoxamine ameliorated both the GMH-induced and iron trichloride-induced decrease of IRP2 and decreased NCBE expressions. Deferoxamine and solute carrier family 4 member 10 small interfering RNA improved cognitive and motor functions at 21 to 28 days post GMH and reduced cerebrospinal fluid production as well as the degree of hydrocephalus at 28 days after GMH. Targeting iron-induced overexpression of NCBE may be a translatable therapeutic strategy for the treatment of PHH following GMH. © 2018 The Authors

  14. Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation.

    Science.gov (United States)

    Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Subota, Vesna; Kataranovski, Dragan; Kataranovski, Milena

    2018-03-01

    Studies of wild animals' immunity often use comparison with laboratory-raised individuals. Using such an approach, various data were obtained concerning wild Norway rat's immunity. Lower or higher potential of immune system cells to respond to activation stimuli were shown, because of analysis of disparate parameters and/ or small number of analyzed individuals. Inconsistent differences between laboratory and wild rats were shown too, owing to great response variability in wild rats. We hypothesized that wild rats will express more intense immune activity compared to their laboratory counterparts which live in a less demanding environment. To test this, we analyzed the circulating levels of inflammatory cytokine interleukin-6 (IL-6), a mediator which has a central role in host immune defense. In addition, we examined the activity of the central immune organ, the spleen, including cell proliferation and production of pro-inflammatory cytokines interferon-γ (IFN-γ) and interleukin-17 (IL-17), which are major effectors of cellular adaptive immune response. In order to obtain reasonable insight into the immunity of wild Norway rats, analysis was conducted on a much larger number of individuals compared to other studies. Higher levels of plasma IL-6, higher spleen mass, cellularity and basal IFN-γ production concomitantly with lower basal production of anti-inflammatory cytokine interleukin-10 (IL-10) revealed more intense immune activity in the wild compared to laboratory rats. However, lower responsiveness of their spleen cells' proinflammatory cytokine production to concanavalin A (ConA) stimulation, along with preserved capacity of IL-10 response, might be perceived as an indication of wild rats' reduced capability to cope with incoming environmental stimuli, but also as a means to limit tissue damage. © 2017 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  15. Obesity reduces bone density associated with activation of PPARγ and suppression of Wnt/β-catenin in rapidly growing male rats.

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    Jin-Ran Chen

    Full Text Available BACKGROUND: It is well established that excessive consumption of a high fat diet (HFD results in obesity; however, the consequences of obesity on postnatal skeletal development have not been well studied. METHODOLOGY AND PRINCIPAL FINDINGS: Total enteral nutrition (TEN was used to feed postnatal day 27 male rats intragastrically with a high 45% fat diet (HFD for four weeks to induce obesity. Fat mass was increased compared to rats fed TEN diets containing 25% fat (medium fat diet, MFD or a chow diet (low fat diet, LFD fed ad libitum with matched body weight gains. Serum leptin and total non-esterified fatty acids (NEFA were elevated in HFD rats, which also had reduced bone mass compared to LFD-fed animals. This was accompanied by decreases in bone formation, but increases in the bone resorption. Bone marrow adiposity and expression of adipogenic genes, PPARγ and aP2 were increased, whereas osteoblastogenic markers osteocalcin and Runx2 were decreased, in bone in HFD rats compared to LFD controls. The diversion of stromal cell differentiation in response to HFD stemmed from down-regulation of the key canonical Wnt signaling molecule β-catenin protein and reciprocal up-regulation of nuclear PPARγ expression in bone. In a set of in vitro studies using pluripotent ST2 bone marrow mesenchymal stromal cells treated with serum from rats on the different diets or using the free fatty acid composition of NEFA quantified in rat serum from HFD-fed animals by GC-MS, we were able to recapitulate our in vivo findings. CONCLUSIONS/SIGNIFICANCE: These observations strongly suggest that increased NEFA in serum from rats made obese by HFD-feeding impaired bone formation due to stimulation of bone marrow adipogenesis. These effects of obesity on bone in early life may result in impaired attainment of peak bone mass and therefore increase the prevalence of osteoporosis later on in life.

  16. Infusion of exogenous cholecystokinin-8, gastrin releasing peptide-29 and their combination reduce body weight in diet-induced obese male rats.

    Science.gov (United States)

    Mhalhal, Thaer R; Washington, Martha C; Newman, Kayla; Heath, John C; Sayegh, Ayman I

    2017-02-01

    We hypothesized that exogenous gastrin releasing peptide-29 (GRP-29), cholecystokinin-8 (CCK-8) and their combination reduce body weight (BW). To test this hypothesis, BW was measured in four groups of diet-induced obese (DIO) male rats infused in the aorta (close to the junctions of the celiac and cranial mesenteric arteries) with saline, CCK-8 (0.5 nmol/kg), GRP-29 (0.5 nmol/kg) and CCK-8+GRP-29 (0.5 nmol/kg each) once daily for a total of 23 days. We found that CCK-8, GRP-29 and CCK-8+GRP-29 reduce BW relative to saline control. In conclusion, CCK-8, GRP-29 and their combination reduce BW in the DIO rat model. If infused near their gastrointestinal sites of action CCK-8, GRP-29 and their combination may have a role in regulating BW. Published by Elsevier Ltd.

  17. Reduced density and altered regulation of rat atrial L-type Ca2+ current in heart failure.

    Science.gov (United States)

    Bond, Richard C; Bryant, Simon M; Watson, Judy J; Hancox, Jules C; Orchard, Clive H; James, Andrew F

    2017-03-01

    Constitutive regulation by PKA has recently been shown to contribute to L-type Ca 2+ current ( I CaL ) at the ventricular t-tubule in heart failure. Conversely, reduction in constitutive regulation by PKA has been proposed to underlie the downregulation of atrial I CaL in heart failure. The hypothesis that downregulation of atrial I CaL in heart failure involves reduced channel phosphorylation was examined. Anesthetized adult male Wistar rats underwent surgical coronary artery ligation (CAL, N =10) or equivalent sham-operation (Sham, N =12). Left atrial myocytes were isolated ~18 wk postsurgery and whole cell currents recorded (holding potential=-80 mV). I CaL activated by depolarizing pulses to voltages from -40 to +50 mV were normalized to cell capacitance and current density-voltage relations plotted. CAL cell capacitances were ~1.67-fold greater than Sham ( P ≤ 0.0001). Maximal I CaL conductance ( G max ) was downregulated more than 2-fold in CAL vs. Sham myocytes ( P 50% more effectively in CAL than in Sham so that differences in I CaL density were abolished. Differences between CAL and Sham G max were not abolished by calyculin A (100 nmol/l), suggesting that increased protein dephosphorylation did not account for I CaL downregulation. Treatment with either H-89 (10 μmol/l) or AIP (5 μmol/l) had no effect on basal currents in Sham or CAL myocytes, indicating that, in contrast to ventricular myocytes, neither PKA nor CaMKII regulated basal I CaL Expression of the L-type α 1C -subunit, protein phosphatases 1 and 2A, and inhibitor-1 proteins was unchanged. In conclusion, reduction in PKA-dependent regulation did not contribute to downregulation of atrial I CaL in heart failure. NEW & NOTEWORTHY Whole cell recording of L-type Ca 2+ currents in atrial myocytes from rat hearts subjected to coronary artery ligation compared with those from sham-operated controls reveals marked reduction in current density in heart failure without change in channel subunit

  18. A rat pancreatic ribonuclease fused to a late cotton pollen promoter severely reduces pollen viability in tobacco plants

    Directory of Open Access Journals (Sweden)

    R.B. Bernd-Souza

    2000-06-01

    Full Text Available The effects of an animal RNase fused to the late cotton pollen-specific promoter G9 in a plant system were investigated. Expression of the chimeric genes G9-uidA and G9-RNase in tobacco plants showed that the 1.2-kb promoter fragment of the G9 gene was sufficient to maintain tissue and temporal specificity in a heterologous system. GUS (beta-glucuronidase expression was detected only in pollen from anther stage 6 through anthesis, with maximal GUS activity in pollen from stage 10 anthers. Investigating the effects of the rat RNase on pollen viability at stage 10, we found that pollen viability was reduced from 79 to 8% and from 89 to 40%, in pollen germination and fluoresceine diacetate assays, respectively, in one G9-RNase transgenic line, suggesting a lethal effect of the RNase gene. This indicates that the rat RNase produces deleterious effects in this plant system and may be useful for engineering male sterility.Foram investigados os efeitos da expressão de uma ribonuclease de origem animal em um sistema vegetal, ligando-se esta ao promotor do gene pólen-específico G9 de algodão. Examinou-se a expressão dos genes quiméricos G9-uidA e G9-RNase em plantas de tabaco e determinou-se que o fragmento de 1.2 kb do promotor do gene G9 foi suficiente para manter a especificidade temporal e espacial da expressão, em sistema heterólogo. A expressão do gene GUS foi detectada somente em pólen, do estágio 6 do desenvolvimento da antera até a antese, com atividade máxima em pólen de anteras no estágio 10. Estudos neste estágio com linhagens transgênicas contendo G9-RNase mostraram que um clone transgênico apresentava reduções na viabilidade do pólen de 79 para 8% e de 89 para 40% nos testes de germinação e coloração com diacetato de fluoresceína, respectivamente, sugerindo letalidade na expressão do gene de RNase. Estes resultados indicam que a RNase animal apresenta um efeito deletério em planta e oferece possibilidade de uso

  19. Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell.

    Science.gov (United States)

    Wilden, Jessica A; Qing, Kurt Y; Hauser, Sheketha R; McBride, William J; Irazoqui, Pedro P; Rodd, Zachary A

    2014-04-01

    There is increasing interest in deep brain stimulation (DBS) for the treatment of addiction. Initial testing must be conducted in animals, and the alcohol-preferring (P) rat meets the criteria for an animal model of alcoholism. This study is composed of 2 experiments designed to examine the effects of 1) pharmacological inactivation and 2) DBS of the nucleus accumbens shell (AcbSh) on the consumption of alcohol by P rats. In the first experiment, the effects of reversible inactivation of the AcbSh were investigated by administering intracranial injections of γ-aminobutyric acid (GABA) agonists. Bilateral microinjections of drug were administered to the AcbSh in P rats (8-10 rats/group), after which the animals were placed in operant chambers containing 2 levers--one used to administer water and the other to administer 15% EtOH--to examine the acquisition and maintenance of oral EtOH self-administration. In the second experiment, a DBS electrode was placed in each P rat's left AcbSh. The animals then received 100 or 200 μA (3-4 rats/group) of DBS to examine the effect on daily consumption of oral EtOH in a free-access paradigm. In the first experiment, pharmacological silencing of the AcbSh with GABA agonists did not decrease the acquisition of EtOH drinking behavior but did reduce EtOH consumption by 55% in chronically drinking rats. Similarly, in the second experiment, 200 μA of DBS consistently reduced EtOH intake by 47% in chronically drinking rats. The amount of EtOH consumption returned to baseline levels following termination of therapy in both experiments. Pharmacological silencing and DBS of the AcbSh reduced EtOH intake after chronic EtOH use had been established in rodents. The AcbSh is a neuroanatomical substrate for the reinforcing effects of alcohol and may be a target for surgical intervention in cases of alcoholism.

  20. European display scene

    Science.gov (United States)

    Bartlett, Christopher T.

    2000-08-01

    The manufacture of Flat Panel Displays (FPDs) is dominated by Far Eastern sources, particularly in Active Matrix Liquid Crystal Displays (AMLCD) and Plasma. The United States has a very powerful capability in micro-displays. It is not well known that Europe has a very active research capability which has lead to many innovations in display technology. In addition there is a capability in display manufacturing of organic technologies as well as the licensed build of Japanese or Korean designs. Finally, Europe has a display systems capability in military products which is world class.

  1. Handbook of display technology

    CERN Document Server

    Castellano, Joseph A

    1992-01-01

    This book presents a comprehensive review of technical and commercial aspects of display technology. It provides design engineers with the information needed to select proper technology for new products. The book focuses on flat, thin displays such as light-emitting diodes, plasma display panels, and liquid crystal displays, but it also includes material on cathode ray tubes. Displays include a large number of products from televisions, auto dashboards, radios, and household appliances, to gasoline pumps, heart monitors, microwave ovens, and more.For more information on display tech

  2. Reduced motivation in the BACHD rat model of Huntington disease is dependent on the choice of food deprivation strategy.

    Science.gov (United States)

    Jansson, Erik Karl Håkan; Clemens, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

    2014-01-01

    Huntington disease (HD) is an inherited neurodegenerative disease characterized by motor, cognitive, psychiatric and metabolic symptoms. Animal models of HD show phenotypes that can be divided into similar categories, with the metabolic phenotype of certain models being characterized by obesity. Although interesting in terms of modeling metabolic symptoms of HD, the obesity phenotype can be problematic as it might confound the results of certain behavioral tests. This concerns the assessment of cognitive function in particular, as tests for such phenotypes are often based on food depriving the animals and having them perform tasks for food rewards. The BACHD rat is a recently established animal model of HD, and in order to ensure that behavioral characterization of these rats is done in a reliable way, a basic understanding of their physiology is needed. Here, we show that BACHD rats are obese and suffer from discrete developmental deficits. When assessing the motivation to lever push for a food reward, BACHD rats were found to be less motivated than wild type rats, although this phenotype was dependent on the food deprivation strategy. Specifically, the phenotype was present when rats of both genotypes were deprived to 85% of their respective free-feeding body weight, but not when deprivation levels were adjusted in order to match the rats' apparent hunger levels. The study emphasizes the importance of considering metabolic abnormalities as a confounding factor when performing behavioral characterization of HD animal models.

  3. Reduced motivation in the BACHD rat model of Huntington disease is dependent on the choice of food deprivation strategy.

    Directory of Open Access Journals (Sweden)

    Erik Karl Håkan Jansson

    Full Text Available Huntington disease (HD is an inherited neurodegenerative disease characterized by motor, cognitive, psychiatric and metabolic symptoms. Animal models of HD show phenotypes that can be divided into similar categories, with the metabolic phenotype of certain models being characterized by obesity. Although interesting in terms of modeling metabolic symptoms of HD, the obesity phenotype can be problematic as it might confound the results of certain behavioral tests. This concerns the assessment of cognitive function in particular, as tests for such phenotypes are often based on food depriving the animals and having them perform tasks for food rewards. The BACHD rat is a recently established animal model of HD, and in order to ensure that behavioral characterization of these rats is done in a reliable way, a basic understanding of their physiology is needed. Here, we show that BACHD rats are obese and suffer from discrete developmental deficits. When assessing the motivation to lever push for a food reward, BACHD rats were found to be less motivated than wild type rats, although this phenotype was dependent on the food deprivation strategy. Specifically, the phenotype was present when rats of both genotypes were deprived to 85% of their respective free-feeding body weight, but not when deprivation levels were adjusted in order to match the rats' apparent hunger levels. The study emphasizes the importance of considering metabolic abnormalities as a confounding factor when performing behavioral characterization of HD animal models.

  4. Early intervention with human albumin to reduce the tissue plasminogen activator-mediated blood-brain barrier permeability damaged by delayed reperfusion: an experimental study in rats

    International Nuclear Information System (INIS)

    Lu Haitao; Zhao Jungong; Li Minghua; Li Yongdong; Zhang Peilei

    2011-01-01

    Objective: To clarify whether early use of high-dose human albumin can reduce the permeability of blood-brain barrier (BBB) damaged by delayed thrombolysis or not, and, in tun, reduce the vasogenic brain edema. Methods: A total of 138 male SD rats weighing 320-380 grams were randomly divided into 4 groups: sham operation group (n=3), control group (n=45), albumin group (n=45) and albumin+rt-PA group (n=45). According to the reperfusion time after the onset of middle cerebral artery occlusion (MCAO), each group, except sham operation group, was divided into three subgroups of 2 h, 3 h and 4 h with 15 rats in each subgroup. Rats in albumin group and albumin+rt-PA group received an intravenous infusion of 20% human albumin (2.5 g/kg) 2 hours after the onset of MCAO, and rats in albumin+rt-PA group received an intravenous infusion of rt-PA (10 mg/kg) at all points of reperfusion time via the rat's femoral vein immediately after the reperfusion. All rats were sacrificed 24 hours after MCAO, the infarct volume of the brain was determined with TTC dye method, the leakage extent of BBB was quantitatively estimated by using Evans blue method, and the matrix metalloproteinase-9 (MMP-9) expression was assessed with immunohistochemistry technique. Results: Early intervention with the use of high-dose human albumin could significantly improve the neurological score at 24 h. In MCAO 3 h albumin group, MCAO 4 h albumin group and MCAO 3 h albumin+rt-PA group, neurological score was significantly better than that in the control group (P 0.05). The volume of the infarct tissue was also significantly smaller in all the treated groups with high-dose human albumin groups (P<0.05) when compared with the control group. The infarct volume of the MCAO 4 h in albumin group and albumin+rt-PA group was reduced by 23% and by 17.3%, respectively. Cerebral hemorrhage transformation occurred in two rats of MCAO 4 h control group, in one rat of MCAO 4 h albumin group and in one rat of MCAO 4 h

  5. Early life seizures in female rats lead to anxiety-related behavior and abnormal social behavior characterized by reduced motivation to novelty and deficit in social discrimination.

    Science.gov (United States)

    Castelhano, Adelisandra Silva Santos; Ramos, Fabiane Ochai; Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo

    2015-03-01

    Previously, we demonstrated that male Wistar rats submitted to neonatal status epilepticus showed abnormal social behavior characterized by deficit in social discrimination and enhanced emotionality. Taking into account that early insult can produce different biological manifestations in a gender-dependent manner, we aimed to investigate the social behavior and anxiety-like behavior in female Wistar rats following early life seizures. Neonate female Wistar rats at 9 days postnatal were subject to pilocarpine-induced status epilepticus and the control received saline. Behavioral tests started from 60 days postnatal and were carried out only during the diestrus phase of the reproductive cycle. In sociability test experimental animals exhibited reduced motivation for social encounter and deficit in social discrimination. In open field and the elevated plus maze, experimental animals showed enhanced emotionality with no changes in basal locomotor activity. The results showed that female rats submitted to neonatal status epipepticus showed impaired social behavior, characterized by reduced motivation to novelty and deficit in social discrimination in addition to enhanced emotionality.

  6. [MK-801 or DNQX reduces electroconvulsive shock-induced impairment of learning-memory and hyperphosphorylation of Tau in rats].

    Science.gov (United States)

    Liu, Chao; Min, Su; Wei, Ke; Liu, Dong; Dong, Jun; Luo, Jie; Liu, Xiao-Bin

    2012-08-25

    This study explored the effect of the excitatory amino acid receptor antagonists on the impairment of learning-memory and the hyperphosphorylation of Tau protein induced by electroconvulsive shock (ECT) in depressed rats, in order to provide experimental evidence for the study on neuropsychological mechanisms improving learning and memory impairment and the clinical intervention treatment. The analysis of variance of factorial design set up two intervention factors which were the electroconvulsive shock (two level: no disposition; a course of ECT) and the excitatory amino acid receptor antagonists (three level: iv saline; iv NMDA receptor antagonist MK-801; iv AMPA receptor antagonist DNQX). Forty-eight adult Wistar-Kyoto (WKY) rats (an animal model for depressive behavior) were randomly divided into six experimental groups (n = 8 in each group): saline (iv 2 mL saline through the tail veins of WKY rats ); MK-801 (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats) ; DNQX (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats ); saline + ECT (iv 2 mL saline through the tail veins of WKY rats and giving a course of ECT); MK-801 + ECT (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats and giving a course of ECT); DNQX + ECT (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats and giving a course of ECT). The Morris water maze test started within 1 day after the finish of the course of ECT to evaluate learning and memory. The hippocampus was removed from rats within 1 day after the finish of Morris water maze test. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. The contents of Tau protein which included Tau5 (total Tau protein), p-PHF1(Ser396/404), p-AT8(Ser199/202) and p-12E8(Ser262) in the hippocampus of rats were detected by immunohistochemistry staining (SP) and Western blot. The results showed that ECT and the glutamate ionic receptor blockers (NMDA receptor antagonist MK-801 and

  7. Reduced estradiol-induced vasodilation and poly-(ADP-ribose polymerase (PARP activity in the aortas of rats with experimental polycystic ovary syndrome (PCOS.

    Directory of Open Access Journals (Sweden)

    Gabriella Masszi

    Full Text Available Polycystic ovary syndrome (PCOS is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT. After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE. Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose polymerase (PARP activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS.

  8. Reduced estradiol-induced vasodilation and poly-(ADP-ribose) polymerase (PARP) activity in the aortas of rats with experimental polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Masszi, Gabriella; Horvath, Eszter Maria; Tarszabo, Robert; Benko, Rita; Novak, Agnes; Buday, Anna; Tokes, Anna-Maria; Nadasy, Gyorgy L; Hamar, Peter; Benyó, Zoltán; Varbiro, Szabolcs

    2013-01-01

    Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT). After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE). Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose) polymerase (PARP) activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS.

  9. A Compressive Superresolution Display

    KAUST Repository

    Heide, Felix; Gregson, James; Wetzstein, Gordon; Raskar, Ramesh; Heidrich, Wolfgang

    2014-01-01

    In this paper, we introduce a new compressive display architecture for superresolution image presentation that exploits co-design of the optical device configuration and compressive computation. Our display allows for superresolution, HDR, or glasses-free 3D presentation.

  10. A Compressive Superresolution Display

    KAUST Repository

    Heide, Felix

    2014-06-22

    In this paper, we introduce a new compressive display architecture for superresolution image presentation that exploits co-design of the optical device configuration and compressive computation. Our display allows for superresolution, HDR, or glasses-free 3D presentation.

  11. [Decursin reduces reactive oxygen species and inhibits cisplatin-induced apoptosis in rat renal tubular epithelial cells].

    Science.gov (United States)

    Li, Cuiqiong; Li, Jianchun; Fan, Junming; Meng, Lifeng; Cao, Ling

    2017-10-01

    Objective To study the mechanism underlying the inhibitory effect of decursin on the apoptosis of rat renal tubular epithelial cells NRK-52E induced by cisplatin. Methods First, CCK-8 assay was used to detect the effects of 0, 10, 20, 40, 80, 100, 150, 200 μmol/L decursin and 0, 5, 10, 20, 30, 40, 50 μg/mL cispatin treatment for 24 hours on cell proliferation in NRK-52E cells via determining the half inhibitory concentration (IC 50 ). Then, NRK-52E cells were stimulated with 20 μg/mL cisplatin combined with 10, 50, 100 μmol/L decursin, and cell activity was detected by CCK-8 assay. The cells were divided into normal control group, 20 μg/mL cisplatin stimulation group, and 10, 50, 100 μmol/L decursin treated groups. Cell morphological changes was observed under inverted microscope, morphological changes of nucleus was detected by DAPI staining, cell apoptosis was detected by flow cytometry, the level of intracellular ROS was detected by DCFH-DA staining, and the apoptosis marker proteins cleaved-caspase-3 and cleaved-PARP were examined by Western blot analysis. Results Compared with the normal control group, cisplatin significantly inhibited the activity of the cells, and IC 50 was about 20 μg/mL; compared with the model group, in the decursin pretreatment groups, the level of intracellular ROS decreased remarkably, the expressions of cleaved-casspase-3 and cleaved-PARP proteins were reduced, and cell apoptosis was depressed. Conclusion Decursin can decrease the intracellular ROS level and inhibit the apoptosis of NRK-52E cells induced by cisplatin.

  12. Pretreatment with remifentanil protects against the reduced-intestinal contractility related to the ischemia and reperfusion injury in rat

    Directory of Open Access Journals (Sweden)

    Hale Sayan-Ozacmak

    2015-12-01

    Full Text Available BACKGROUND AND OBJECTIVES: Serious functional and structural alterations of gastrointestinal tract are observed in failure of blood supply, leading to gastrointestinal dismotility. Activation of opioid receptors provides cardioprotective effect against ischemia-reperfusion (I/R injury. The aim of the present study was to determine whether or not remifentanil could reduce I/R injury of small intestine. METHODS: Male Wistar Albino rats were subjected to mesenteric ischemia (30 min followed by reperfusion (3 h. Four groups were designed: sham control; remifentanil alone; I/R control; and remifentanil + I/R. Animals in remifentanil + I/R group were subjected to infusion of remifentanil (2 ug kg-1 min-1 for 60 min, half of which started before inducing ischemia. Collecting the ileum tissues, evaluation of damage was based on contractile responses to carbachol, levels of lipid peroxidation and neutrophil infiltration, and observation of histopathological features in intestinal tissue. RESULTS: Following reperfusion, a significant decrease in carbachol-induced contractile response, a remarkable increase in both lipid peroxidation and neutrophil infiltration, and a significant injury in mucosa were observed. An average contractile response of remifentanil + I/R group was significantly different from that of the I/R group. Lipid peroxidation and neutrophil infiltration were also significantly suppressed by the treatment. The tissue samples of the I/R group were grade 4 in histopathological evaluation. In remifentanil + I/R group, on the other hand, the mucosal damage was moderate, staging as grade 1. CONCLUSIONS: The pretreatment with remifentanil can attenuate the intestinal I/R injury at a remarkable degree possibly by lowering lipid peroxidation and leukocyte infiltration.

  13. Liquid crystal display

    International Nuclear Information System (INIS)

    Takami, K.

    1981-01-01

    An improved liquid crystal display device is described which can display letters, numerals and other necessary patterns in the night time using a minimized amount of radioactive material. To achieve this a self-luminous light source is placed in a limited region corresponding to a specific display area. (U.K.)

  14. Intravenous Infusion of Bone Marrow–Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats

    OpenAIRE

    Yohei Matsuda, MD; Masanori Sasaki, MD, PhD; Yuko Kataoka-Sasaki, MD, PhD; Akio Takayanagi, MD, PhD; Ko Kobayashi, MD, PhD; Shinichi Oka, MD, PhD; Masahito Nakazaki, MD, PhD; Naoya Masumori, MD, PhD; Jeffery D. Kocsis, PhD; Osamu Honmou, MD, PhD

    2018-01-01

    Introduction: Intravenous preload (delivered before cavernous nerve [CN] injury) of bone marrow–derived mesenchymal stem cells (MSCs) can prevent or decrease postoperative erectile dysfunction (J Sex Med 2015;12:1713–1721). In the present study, the potential therapeutic effects of intravenously administered MSCs on postoperative erectile dysfunction were evaluated in a rat model of CN injury. Methods: Male Sprague-Dawley rats were randomized into 2 groups after electric CN injury. Intrave...

  15. The Anticholinergic and Antiglutamatergic Drug Caramiphen Reduces Seizure Duration in Soman-Exposed Rats: Synergism with the Benzodiazepine Diazepam

    Science.gov (United States)

    2012-01-01

    progress to self-sustained seizures ( status epilepticus , SE) and result in extensive neuropathology as seen in rats (de Araujo Furtado et al., 2009, 2010...physostigmineOP organophosphorus BuChE butyrylcholinesterase ChE cholinesterase SE status epilepticus ATR atropine sulfate 2-PAM 2-pralidoxime NMDA N...L.C., Lichtenstein, S., Yourick, D.L., 2010. Spontaneous recurrent seizures after status epilepticus induced by soman in Sprague-Dawley rats

  16. Consortium for military LCD display procurement

    Science.gov (United States)

    Echols, Gregg

    2002-08-01

    International Display Consortium (IDC) is the joining together of display companies to combined their buying power and obtained favorable terms with a major LCD manufacturer. Consolidating the buying power and grouping the demand enables the rugged display industry of avionics, ground vehicles, and ship based display manufacturers to have unencumbered access to high performance AMLCDs while greatly re