JNK3 Is Required for the Cytoprotective Effect of Exendin 4.

Preservation of beta cell against apoptosis is one of the therapeutic benefits of the glucagon-like peptide-1 (GLP1) antidiabetic mimetics for preserving the functional beta cell mass exposed to diabetogenic condition including proinflammatory cytokines. The mitogen activated protein kinase 10 also called c-jun amino-terminal kinase 3 (JNK3) plays a protective role in insulin-secreting cells against death caused by cytokines. In this study, we investigated whether the JNK3 expression is associated with the protective effect elicited by the GLP1 mimetic exendin 4. We found an increase in the abundance of JNK3 in isolated human islets and INS-1E cells cultured with exendin 4. Induction of JNK3 by exendin 4 was associated with an increased survival of INS-1E cells. Silencing of JNK3 prevented the cytoprotective effect of exendin 4 against apoptosis elicited by culture condition and cytokines. These results emphasize the requirement of JNK3 in the antiapoptotic effects of exendin 4.

The cytoprotective effect of alpha-tocopherol and daidzein against d-galactosamine-induced oxidative damage in the rat liver

We hypothesized that the hepatotoxicity that develops after the induction of oxidative stress (induced by d-galactosamine [GalN]) can be ameliorated by alpha-tocopherol (ATC) and the soy isoflavone daidzein. To test this, we ranked and assigned male Wistar rats into 6 groups, which involved pretreatment (ATC or daidzein) for 1 hour followed by treatment (GalN) for 23 hours. Histopathologic analysis showed that GalN administration induced marked necrosis (P < .001), steatosis (P < .001), both lobular and portal inflammations (P < .001), overall histopathologic score (P < .001), and activation of caspase-3 in the liver (P < .001). Immunohistochemical staining of malondialdehyde-protein adducts, a measure of oxidative stress, was increased in response to GalN (P < .001). Paradoxically, there were increases in total (P < .05) and cytosolic superoxide dismutase (P < .001) activities after GalN administration, indicative of an up-regulation of antioxidant defenses. The concentration of total protein (P < .001), albumin (P < .01), and globulin fractions (P < .001) in the plasma, as well as the activity of aspartate aminotransferase (P < .001), was significantly perturbed after GalN treatment, reflective of overall acute hepatic injury. Administration of daidzein showed a significant amelioration of the Ga1N-induced increase in malondialdehyde-protein adducts (P < .01) and cytosolic superoxide dismutase activities (P < .01) in the liver. However, all other variables were not significantly altered in response to daidzein. In response to ATC pretreatment, the total histopathologic score (P < .05), degree of necrosis (P < .05), and both lobular (P < .05) and portal (P = .05) inflammations were significantly ameliorated. To conclude, both daidzein and ATC protect the liver against oxidative damage possibly via different pathways.

Ascorbic acid supplementation has a cytoprotective effect on secondary biliary cirrhosis: experimental study in young rats

Objective: To test whether ascorbic acid supplementation has any cytoprotective effect on a model of secondary biliary cirrhosis in young rats.Methods: We studied 40 Wistar rats weaned at the 21st postnatal day. Each group of 10 was subjected to one of the following four treatments, until 49th postnatal day, when they suffered euthanasia: 1) LC-double ligature and resection of the common bile duct and daily administration of ascorbic acid [100 mg/g of body weight (bw)]; 2) LA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw); 3) SC-sham operation and daily administration of ascorbic acid (100 mg/g bw); 4) SA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw). The rats were weighed daily. on the 27th day after the operation they received an intra-peritoneal injection of 1.5 mg/g bw of sodium pentobarbital, and the pentobarbital sleeping time was measured. Blood was collected for serum alanine aminotransferase and aspartate aminotransferase activity measurements, serum albumin and globulin concentrations, and the liver was assessed for liver water and fat content. Data were submitted to two-way ANOVA and paired comparisons between groups were tested using the SNK method. Significance level was set at 0.05.Results: Ascorbic acid supplementation attenuated the effects of cholestasis: decreased the pentobarbital sleeping time, serum globulin, and the liver fat content.Conclusions: Our results corroborate the hypothesis that ascorbic acid supplementation has a cytoprotective effect in secondary biliary cirrhosis.

Antiulcerogenic effect and cytotoxic activity of semi-synthetic crotonin obtained from Croton cajucara Benth.

Trans-dehydrocrotonin, the major diterpene isolated from the bark of Croton cajucara, has good antiulcerogenic activity which, however, is accompanied by toxic effects. on the basis of these results, a semi-synthetic crotonin, named 4SRC, was prepared to determine whether this substance has similar antiulcerogenic activity with lower or no toxicity. The natural crotonin was also isolated from the bark of C. cajucara but was not used due to the small amount obtained. The cytotoxic effect of semi-synthetic crotonin, expressed as cell viability, was assessed in (a) lung fibroblast cell line (V79) derived from Chinese hamsters, a system commonly used for cytotoxicity studies, and (b) rat hepatocytes isolated from male Wistar rats. After treatment, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction (MTT reduction), total acid content and neutral red uptake assays. To evaluate V79 cell viability, different concentrations of semi-synthetic crotonin were incubated with the cells. To evaluate the antiulcerogenic effects of semi-synthetic crotonin (50, 100 and 200 mg/kg), we used the models of gastric ulcer induced by ethanol/HCl, stress, indomethacin/bethanechol, and ethanol in male Swiss mice and male Wistar rats. The substance had an IC50 = 500 muM in the neutral red uptake and MTT reduction tests and an IC50 = 200 muM in the nucleic acid content test. With regard to hepatocyte viability after treatment with semi-synthetic crotonin at different concentrations, semi-synthetic crotonin had an IC50 = 10-500 muM in the nucleic acid content and MTT reduction tests and an IC50 = 120 muM in the neutral red uptake test. In another experiment, V79 cells were incubated with the metabolites produced by hepatocytes treated with different concentrations of semi-synthetic crotonin. After a 4-h incubation, semi-synthetic crotonin had an IC50 = 500 muM in the MTT reduction and neutral red uptake tests and an IC50 = 370 muM in nucleic acid content test. The substance had significant antiulcerogenic activity in all models studied, suggesting the presence of a possible antisecretory effect combined with a cytoprotective effect. For this reason, the effect of semi-synthetic crotonin was also evaluated on biochemical parameters of gastric juice and gastric wall mucus, both obtained from pylorus-ligated mice. No significant differences were observed in these parameters between semi-synthetic crotonin-treated and control animals. The results obtained with semi-synthetic crotonin are promising, with a significant preventive effect against gastric ulcer induced by different agents. Our data also show that semi-synthetic crotonin was less toxic than dehydrocrotonin and that the cytotoxic effects decreases with the time that isolated hepatocytes were in culture. (C) 2003 Elsevier B.V. B.V. All rights reserved.

Up-regulation of p21(WAF1)/(CIP1) by histone deacetylase inhibitors reduces their cytotoxicity

Histone deacetylase inhibitors show promise as chemotherapeutic agents and have been demonstrated to block proliferation in a wide range of tumor cell lines. Much of this antiproliferative effect has been ascribed to the up-regulated expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1). In this article, we report that p21 expression was up-regulated by relatively low doses of the histone deacetylase inhibitor azelaic bishydroxamic acid (ABHA) and correlated with a proliferative arrest. Higher doses of ABHA were cytotoxic. Cells that did not up-regulate p21 expression were hypersensitive to killing by ABHA and died via apoptosis, whereas up-regulation of p21 correlated with reduced sensitivity and a block in the apoptotic mechanism, and these cells seemed to die by necrosis. Using isogenic p21(+/+) and p21(-/-) cell lines and direct inhibition of caspase activity, we demonstrate that the reduced sensitivity to killing by ABHA is a consequence of inhibition of apoptosis by up-regulated p21 expression. These data indicate the enormous potential of therapeutic strategies that bypass the cytoprotective effect of p21 and act on the same molecular targets as the histone deacetylase inhibitors.

Carbon monoxide, autophagy and cytoprotection in response to cerebral ischemia

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Proteomic analysis of a neurodegeneration cell model, treated with plant extracts with potential neuroprotective activity

Nowadays, a significant increase in chronic diseases is observed. Epidemiological studies showed a consistent relationship between the consumption of fruits and vegetables and a reduced risk of certain chronic diseases, namely neurodegenerative disorders. One factor common to these diseases is oxidative stress, which is highly related with proteins, lipids, carbohydrates and nucleic acids damage, leading to cellular dysfunction. Polyphenols, highly abundant in berries and associated products, were described as having antioxidant properties, with beneficial effect in these pathologies. The aims of this study were to evaluate by proteomic analyses the effect of oxidative insult in a neuroblastoma cell line (SK-N-MC) and understand the mechanisms involved in the neuroprotective effects of digested extracts from commercial and wild blackberry (R. vagabundus Samp.). The analysis of the total proteome by two-dimensional electrophoresis revealed that oxidative stress in SK-N-MC cells resulted in altered expression of 12 protein spots from a total of 318. Regarding some redox proteomics alterations, particularly proteins carbonylation and glutathionylation, protein carbonyl alterations during stress suggest that cells produce an early and late response; on the other hand, no glutathionylated polypeptides were detected. Relatively to the incubation of SK-N-MC cells with digested berry extracts, commercial blackberry promotes more changes in protein pattern of these cells than R. vagabundus. From 9 statistically different protein spots of cells incubated with commercial blackberry, only β-tubulin and GRP 78 were until now identified by mass spectrometry. Further studies involving the selection of sub proteomes will be necessary to have a better understanding of the mechanisms underlying the neuroprotective effects of berries.

Role and regulation of islet-Brain 1 in pancreatic β-cells

Résumé : L'insuline est produite et sécrétée par la cellule ß-pancréatique. Son rôle est de régler le taux de sucre dans le sang. Si ces cellules meurent ou échouent à produire suffisamment de l'insuline, les sujets développent le diabète de type 2 (DT2), une des maladies les plus communes dans les pays développés. L'excès chronique des lipoprotéines LDL oxydés (oxLDL) et/ou des cytokines pro-inflammatoires comme l'interleukine-1ß (IL-1ß) participent au dérèglement et à la mort des cellules ß. Nous avons montré qu'une chute des niveaux d'expression de la protéine nommée «mitogen activated protein kinase 8 interacting protein 1» ou «islet brain 1 (IB 1)» est en partie responsable des effets provoqués par les oxLDL ou IL-1ß. IB1 régule l'expression de l'insuline et la survie cellulaire en inhibant la voie de signalisation « c-jun N-terminal Kinase (JNK)». La réduction des niveaux d'expression d'IB1 provoque l'activation de la voie JNK en réponse aux facteurs environnementaux, et ainsi initie la réduction de l'expression de l'insuline et l'induction du programme de mort cellulaire. Les mimétiques de l'hormone "Glucagon-like peptide 1", tel que l'exendin-4 (ex-4), sont une nouvelle classe d'agents hypoglycémiants utilisés dans le traitement du DT2. Les effets bénéfiques de l'ex-4 sont en partie accomplis en préservant l'expression de l'insuline et la survie des cellules ß contre les stress associés au DT2. La restauration des niveaux d'expression d'IB1 est un des mécanismes par lequel l'ex-4 prodigue son effet sur la cellule. En effet, cette molécule stimule l'activité du promoteur du gène et ainsi compense la réduction du contenu en IB1 causée par le stress. Outre ce rôle anti-apoptotique, dans ce travail de thèse nous avons mis en évidence une autre fonction d'IB1 dans la cellule ß. La réduction de l'activité ou des niveaux d'expression d'IB1 induisent une réduction importante de la sécrétion de l'insuline en réponse au glucose. Le mécanisme par lequel IB1 régule la sécrétion de l'insuline implique à la fois le métabolisme du glucose et éventuellement le transport vésiculaire en contrôlant l'expression de la protéine annexin A2. En résumé, IB 1 est une molécule clé à travers laquelle l'environnement du diabétique pourrait exercer un effet délétère sur la cellule ß. L'amélioration de l'activité d'IB1 et/ou de son expression devrait être considérée dans les approches thérapeutiques futures visant à limiter la perte des cellules ß dans le diabète. Abstract : ß-cells of the pancreatic islets of Langerhans produce and secrete insulin when blood glucose rises. In turn, insulin ensures that plasma glucose concentrations return within a relatively narrow physiological range. If ß-cells die or fail to produce enough insulin, individuals develop one of the most common diseases in Western countries, namely type 2 diabetes (T2D). Chronic excess of oxidized low density lipoproteins (oxLDL) and/or pro-inflammatory cytokines such as interleukin 1-ß (IL-1ß) contribute to decline of ß-cells and thereby are thought to accelerate progression of the disease overtime. We showed that profound reduction in the levels of the mitogen activated protein kinase 8 interacting protein 1 also called islet brain 1 (IB1) causes ß-cell failure accomplished by oxLDL or IL-1 ß. IB1 regulates insulin expression and cell survivals by inhibiting the c-Jun N-terminal Kinase pathway. Diminution in IB 1 levels leads to an increase in activation of the JNK pathway induced by environmental stressors, and thus initiates loss of insulin expression and programmed cell death. The mimetic agents of the glucoincretin glucagon-like peptide 1 such as exendin-4 (ex-4) are new class of hypoglycaemic medicines for treatment of T2D. The beneficial property is in part achieved by preserving insulin expression and ß-cell survival against stressors related to diabetes. Restored levels in IB 1 account for the cytoprotective effect of the ex-4. In fact, the latter molecule .stimulates the promoter activity of the gene and thus compensates loss of IB1 content triggered by stress. Beside of the anti-apoptotic role, an additional leading function for IB 1 in ß-cells was highlighted in this thesis. Impairment in IB1 activity or silencing of the gene in ß-cells revealed a major reduction in insulin secretion elicited by glucose. The mechanisms whereby IB 1 couples glucose to insulin release involve glucose metabolism and potentially, vesicles trafficking by maintaining the levels of annexin A2. IB 1 is therefore a key molecule through which environmental factors related to diabetes may exert harmful effects on ß-cells. Improvement in IB 1 activity and/or expression should be considered as a target for therapeutic purpose.

Brain tumor and brain endothelial cells' response to ionizing radiation and phytochemical treatments

Le glioblastome multiforme (GBM) représente la tumeur cérébrale primaire la plus agressive et la plus vascularisée chez l’adulte. La survie médiane après le diagnostic est de moins d’un an en l’absence de traitement. Malheureusement, 90% des patients traités avec de la radiothérapie après la résection chirurgicale d’un GBM développent une récidive tumorale. Récemment, le traitement des GBM avec radiothérapie et témozolomide, un agent reconnu pour ses propriétés antiangiogéniques, a permis de prolonger la survie médiane à 14,6 mois. Des efforts sont déployés pour identifier des substances naturelles capables d’inhiber, de retarder ou de renverser le processus de carcinogenèse. Epigallocatechin-3-gallate (EGCG), un polyphénol retrouvé dans le thé vert, est reconnu pour ses propriétés anticancéreuses et antiangiogéniques. L’EGCG pourrait sensibiliser les cellules tumorales cérébrales et les cellules endothéliales dérivées des tumeurs aux traitements conventionnels. Le chapitre II décrit la première partie de ce projet de doctorat. Nous avons tenté de déterminer si l’EGCG pourrait sensibiliser la réponse des GBM à l’irradiation (IR) et si des marqueurs moléculaires spécifiques sont impliqués. Nous avons documenté que les cellules U-87 étaient relativement radiorésistantes et que Survivin, une protéine inhibitrice de l’apoptose, pourrait être impliquée dans la radiorésistance des GBM. Aussi, nous avons démontré que le pré-traitement des cellules U-87 avec de l’EGCG pourrait annuler l’effet cytoprotecteur d’une surexpression de Survivin et potentialiser l’effet cytoréducteur de l’IR. Au chapitre III, nous avons caractérisé l’impact de l’IR sur la survie de cellules endothéliales microvasculaires cérébrales humaines (HBMEC) et nous avons déterminé si l’EGCG pouvait optimiser cet effet. Bien que les traitements individuels avec l’EGCG et l’IR diminuaient la survie des HBMEC, le traitement combiné diminuait de façon synergique la survie cellulaire. Nous avons documenté que le traitement combiné augmentait la mort cellulaire, plus spécifiquement la nécrose. Au chapitre IV, nous avons investigué l’impact de l’IR sur les fonctions angiogéniques des HBMEC résistantes à l’IR, notamment la prolifération cellulaire, la migration cellulaire en présence de facteurs de croissance dérivés des tumeurs cérébrales, et la capacité de tubulogenèse. La voie de signalisation des Rho a aussi été étudiée en relation avec les propriétés angiogéniques des HBMEC radiorésistantes. Nos données suggèrent que l’IR altère significativement les propriétés angiogéniques des HBMEC. La réponse aux facteurs importants pour la croissance tumorale et l’angiogenèse ainsi que la tubulogenèse sont atténuées dans ces cellules. En conclusion, ce projet de doctorat confirme les propriétés cytoréductrices de l’IR sur les gliomes malins et propose un nouveau mécanisme pour expliquer la radiorésistance des GBM. Ce projet documente pour la première fois l’effet cytotoxique de l’IR sur les HBMEC. Aussi, ce projet reconnaît l’existence de HBMEC radiorésistantes et caractérise leurs fonctions angiogéniques altérées. La combinaison de molécules naturelles anticancéreuses et antiangiogéniques telles que l’EGCG avec de la radiothérapie pourrait améliorer l’effet de l’IR sur les cellules tumorales et sur les cellules endothéliales associées, possiblement en augmentant la mort cellulaire. Cette thèse supporte l’intégration de nutriments avec propriétés anticancéreuses et antiangiogéniques dans le traitement des gliomes malins pour sensibiliser les cellules tumorales et endothéliales aux traitements conventionnels.

Flavonoids from the leaves of Deguelia utilis (Leguminosae): structural elucidation and neuroprotective properties

Das folhas de Deguelia utilis foram isolados cinco flavonoides: 5,3'-di-hidróxi-4'-metóxi2'',2''-dimetilcromeno-(5'',6'':6,7)-di-hidroflavonol (1), 5,3'-di-hidróxi-7,4'-dimetóxi-6,8dimetilalil-di-hidroflavonol (2), 5,3'-di-hidróxi-4'-metóxi-8-prenil-2'',2''-dimetilcromeno(5'',6'':6,7)-flavanona (3), 5,3'-di-hidróxi-7,4'-dimetóxi-6,8-dimetilalil-flavanona (4), 3,5,3'-tri-hidróxi-7,4'-dimetóxi-6,8-dimetilalil-flavanol (5), juntamente com os estilbenos: 4-metoxilonchocarpeno (6) e lonchocarpeno (7). Suas estruturas químicas foram elucidadas com base nos seus dados de NMR (ressonância magnética nuclear) e HRESITOF-MS (espectrometria de massas de alta resolução por tempo de vôo, com ionização por eletrospray). Além disso, a fim de investigar o potencial efeito citoprotetor desses flavonoides, foi utilizada uma fração eluída com hexano:AcOEt contendo os sete flavonoides, em um modelo in vitro de neurodegeneração, utilizando culturas primárias do hipocampo de ratos neonatal (PND2-P3) expostos à rotenona, um inibidor mitocondrial do complexo I. Houve uma redução significativa da viabilidade celular (19,4 ± 1,6%), quando as culturas foram expostas à rotenona 30 nmol L^-1 por 72 h. A exposição concomitante das culturas a FR3 (5 µg mL^-1) e rotenona 30 nmol L^-1 resultou em valores de viabilidade celular semelhante ao grupo controle (99,6 ± 4,8%), sugerindo um efeito citoprotetor para essa fração.

Use of HEPG2 cells to assay the safety of cosmetic active substances

The importance of this study is based on the need to obtain simple and efficient in vitro models to predict the in vivo toxicity of cosmetics, aiming not to use animals as experimental model. Here, we proposed the use of HepG2 cells, which are widely applied to simulate the hepatic function of the human organism in vitro. This cell line was chose since recent studies have shown that the liver is potentially the most frequently targeted organ by cosmetic ingredients, and beyond that, considering the widely application of in vitro assays to test the cutaneous permeation of cosmetic products, including the assays applying modified Franz cells, this technique becomes indispensable. Three different cosmetic active substances were used, and the toxicity to HepG2 cells was assessed by the MTT method. The treatment with hyaluronic acid showed no toxicity to HepG2 cells. Treating the cells with P. guajava L. extract were verified that increasing the amount of the extract in the media, the cellular viability decreased, and finally, the treatment of alpha-lipoic acid showed a cytoprotective effect in relation to the treatment with propylene glycol. The study demonstrated the suitability in using HepG2 cells to assess the safety of cosmetic active substances, helping in the prediction of if the substance could be hepatotoxic if could reach the bloodstream

Nitric oxide reduces oxidative damage induced by water stress in sunflower plants

Drought is one of the main environmental constraints that can reduce plant yield. Nitric oxide (NO) is a signal molecule involved in plant responses to several environmental stresses. The objective of this study was to investigate the cytoprotective effect of a single foliar application of 0, 1, 10 or 100 µM of the NO donor sodium nitroprusside (SNP) in sunflower plants under water stress. Water stressed plants treated with 1μM SNP showed an increase in the relative water content compared with 0 μM SNP. Drought reduced the shoot dry weight but SNP applications did not result in alleviation of drought effects. Neither drought nor water stress plus SNP applications altered the content of photosynthetic pigments. Stomatal conductance was reduced by drought and this reduction was accompanied by a significant reduction in intercellular CO2 concentration and photosynthesis. Treatment with SNP did not reverse the effect of drought on the gas exchange characteristics. Drought increased the level of malondialdehyde (MDA) and proline and reduced pirogalol peroxidase (PG-POD) activity, but did not affect the activity of superoxide dismutase (SOD). When the water stressed plants were treated with 10 μM SNP, the activity of PG-POD and the content of proline were increased and the level of MDA was decreased. The results show that the adverse effects of water stress on sunflower plants are dependent on the external NO concentration. The action of NO may be explained by its ability to increase the levels of antioxidant compounds and the activity of ROS-scavenging enzymes.

Low molecular weight dextran sulfate as complement inhibitor and cytoprotectant in solid organ and islet transplantation

Complement is an essential part of the innate immune system and plays a crucial role in organ and islet transplantation. Its activation, triggered for example by ischemia/reperfusion (I/R), significantly influences graft survival, and blocking of complement by inhibitors has been shown to attenuate I/R injury. Another player of innate immunity are the dendritic cells (DC), which form an important link between innate and adaptive immunity. DC are relevant in the induction of an immune response as well as in the maintenance of tolerance. Modulation or inhibition of both components, complement and DC, may be crucial to improve the clinical outcome of solid organ as well as islet transplantation. Low molecular weight dextran sulfate (DXS), a well-known complement inhibitor, has been shown to prevent complement-mediated damage of the donor graft endothelium and is thus acting as an endothelial protectant. In this review we will discuss the evidence for this cytoprotective effect of DXS and also highlight recent data which show that DXS inhibits the maturation of human DC. Taken together the available data suggest that DXS may be a useful reagent to prevent the activation of innate immunity, both in solid organ and islet transplantation.

Biochemical Studies on the Protective Effect of Taurine on Experimentally Induced Myocardial infarction in Rats

The present study indicate that prior administration of taurine is effective in minimizing all the deleterious effects induced by isoproterenol, thereby justifying its use as a potent cytoprotective agent. The overall cardioprotective effect of taurine is probably related to its antioxidant property evidenced by its ability to reduce lipid peroxidation and to maintain the activities of free radical enzymes and nonenzymatic antioxidants, its membrane stabilizing action and to its hypolipidemic property.

Biochemical Studies on the Protective Effect of Taurine on Experimentally Induced Fulminat Hepatic Failure in Rats

Fulminant hepatic failure (FHF) is a dramatic and challenging syndrome in clinical medicine. Although an uncommon disorder, it is usually fatal and occurs in previously healthy person. While the causes of FHF remain unclear, viral hepatitis and drug-induced liver injury account for the majority of cases. Hepatitis E causes large-scale epidemics of hepatitis in the Indian subcontinent, involving hundreds of thousands of cases with high mortality. FHF is associated with several clinical features like jaundice, shrunken liver, easy bruising, low levels of serum proteins, fatigue, multi-organ failure etc and metabolic derangements like hypoglycemia, hyperlipidemia, hyponatremia, defective protein synthesis, reduced energy production, decreased rate of urea production etc. These disturbances are predominantly attributed to oxidative stress, membrane destabilization and osmolytic imbalances. The options available for these patients are quite minimal with liver transplantation being one of them. But the procedure is ridden with issues causing it to find less favor among the patients and the caregivers. Use of hepatoprotective and cytoprotective drugs, is being considered to be a more acceptable alternative as a strategy to enhance liver regeneration. In this regard use of taurine a naturally occurring amino acid that plays a crucial role in many physiological processes would prove to be effective. In the present study, hepatoprotective effect of taurine on a rat model of induced FHF was studied. Taurine supplementation has effectively counteracted the metabolic and structural aberrations in the liver caused by D-galactosamine intoxication.