Renal carcinogenesis induced by ferric nitrilotriacetate in mice, and protection from it by Brazilian propolis and artepillin C

The protective effect of Brazilian propolis and its extract Artepillin C against ferric nitrilotriacetate (Fe-NTA)-induced renal lipid peroxidation and carcinogenesis was studied in male ddY mice. Fe-NTA-induced renal lipid peroxidation leads to a high incidence of renal cell carcinoma (RCC) in mice. Administration of propolis by gastric intubation 2 h before or Artepillin C at either the same time, 2 h, or 5 h before the intraperitoneal injection of Fe-NTA (7 mg Fe/kg) effectively inhibited renal lipid peroxidation. This was evaluated from the measurement of renal thiobarbituric acid-reactive substances (TBARS) or histochemical findings of 4-hydroxy-2-nonenal (4-HNE)-modified proteins and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Repeated injection of Fe-NTA (10 mg Fe/kg per day, twice a week for a total of 16 times in 8 weeks) caused subacute nephrotoxicity as revealed by necrosis and pleomorphic large nuclear cells in the renal proximal tubules, and gave rise to RCC 12 months later. A protective effect from carcinogenicity was observed in mice given propolis or Artepillin C. Furthermore, the mice given Fe-NTA only developed multiple cysts composed of precancerous lesions with multilayered and proliferating large atypical cells. Mice treated with propolis and Artepillin C also had cysts, but these were dilated and composed of flat cells. These results suggest that propolis and Artepillin C prevent oxidative renal damage and the carcinogenesis induced by Fe-NTA in mice.     

Enhanced testicular antioxidant system by ascorbic acid in alloxan diabetic rats

The diabetic subject is at significantly increased risk of developing testicular changes. Its etiology may involve oxidative damage by free radicals and protection against such damage can be offered by antioxidant supplementation. Alloxan elicited significant inhibition of antioxidants including superoxide dismutase, catalase and glutathione reductase activities and decreased glutathione content in testis. These effects were accompanied by significant elevation of testicular lipid peroxidation, decreased plasma testosterone level and a drop in copper and zinc concentrations in testis. The administration of ascorbic acid after alloxan treatment interfered and prevented alloxan action. Ascorbic acid blunted the increased testicular lipid peroxidation and the decreased plasma testosterone level probably by protecting antioxidants and the loss of copper and zinc from testes. The data suggested that ascorbic acid has a protective effect on alloxan-induced damage by maintaining the activity of cellular antioxidants.     

Oxidative stress induced by fluoride in adult mice and their suckling pups.

To assess renal and liver damages in pregnant and lactating mice as well as in their suckling pups, Wistar female mice were given 500 ppm NaF (226 ppm F-) in drinking water from the 15th day of pregnancy until day 14 after delivery. All mice were sacrificed on day 14 after parturition. In the present work, we evaluated the effects of sodium fluoride on histopathological aspects of kidney, antioxidant status, lipid peroxidation levels and on the expression of four stress proteins (namely, the cytosolic heat shock proteins: HSP72, 73, 90 and the reticulum-associated GRP94). Histological studies have shown many abnormalities in mothers and their pups. Biochemical results showed that lipid peroxidation increased in NaF-treated mice, as evidenced by high kidney and liver thiobarbituric acid reactive substance (TBARS) levels. Alteration of the antioxidant system was confirmed by the significant decline of serum total antioxidant status and of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in red blood cells. Besides, fluoride treatment induced a decrease in serum levels of non-enzymatic antioxidants such as uric acid and of some oligoelements: zinc and copper, known to be cofactors of superoxide dismutase (SOD-Cu-Zn). Compared to control group, the 72kDa protein was found to be overexpressed in kidney of 14-day-old mice only. HSP90 expression in liver appeared moderately inhibited in mothers, but decreased significantly in their pups. No significant changes were detected in the expression of 94kDa protein in both liver and kidney. Results showed that fluoride given to dams led to an oxidative stress in mothers as well as in offspring able to induce enhanced lipid peroxidation levels and protein conformational changes, as suggested by stress protein (HSP, GRP) expression changes.     

Artemisia campestris leaf extract alleviates early diabetic nephropathy in rats by inhibiting protein oxidation and nitric oxide end products

Chronic hyperglycemia in diabetes leads to free radicals overproduction, which contributes to the development of diabetic nephropathy. The present study investigated the effects of Artemisia campestris (Ac), a plant of the Asteraceae family, on renal impairment and oxidative stress in alloxan-induced diabetic rats. Diabetes was induced by a single subcutaneous injection of alloxan (120 mg kg(-1)) in rats. Ac (200 mg kg(-1)) was administered to diabetic rats for 3 weeks. Diabetic renal injury was associated with hyperglycemia, increased serum creatinine, urea and uric acid levels. This nephropathophysiology was associated with a surproduction of nitric oxide (NO), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels and a decrease in glutathione (GSH) levels. In addition, hyperglycemia increased the activities of antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), in the kidney of diabetic rats. Treatment with Ac effectively ameliorated diabetic renal dysfunction by reducing oxidative and nitrosative stress. Histological studies also supported the experimental findings. The results suggested that Ac might act as a beneficial agent against renal dysfunctions developed in alloxan-induced diabetes.     

Inhibition of δ-aminolevulinate dehydratase is not closely related to the development of hyperglycemia in alloxan-induced diabetic mice

Alloxan is a compound widely used in models of diabetes mellitus due to its ability for damage insulin-producing β-cells. The aim of this study was to investigate acute (after 24 h) and sub-acute (after seven days) effects of 200 mg/kg alloxan administration on mice. Biochemical parameters as liver, kidney, and blood δ-ALA-D activity, total sulfhydryl content of hepatic and renal tissues, and hepatic and renal content of malondialdehyde (MDA) were evaluated. The histopathology of hepatic and renal tissues of alloxan-treated and control animals was carried out. Further, blood glucose levels were determined in an attempt to correlate alloxan-induced hyperglycemia with changes in thiol status. Results showed that mice exhibited a significant inhibition of hepatic and renal δ-ALA-D activity in addition to a significant decrease in total sulfhydryl groups of same tissues in both acute and sub-acute alloxan administrations. Moreover, alloxan-induced inhibition of δ-ALA-D activity was partly suppressed when enzymatic assay was performed in the presence of dithiothreitol, suggesting that inhibitory effect of alloxan on δ-ALA-D activity is, at least partially, related to the oxidation of the enzyme’s essential thiol groups. Blood δ-ALA-D activity was significantly inhibited only 24 h after alloxan administration; however, at this time, a hyperglycemic status was not observed in animals. In contrast, a significant increase in blood glucose levels was observed seven days after alloxan administration. Despite of alterations in biochemical parameters, histological tissue examination of alloxan-treated mice revealed typical renal and hepatic parenchyma. Therefore, these results showed that acute toxic effects of alloxan are related, at least partially, to depletion of sulfhydryl groups, and do not closely relate to the development of hyperglycemia in mice.     

The effect of cherry sticks extract on the levels of glycoproteins in alloxan-induced experimental diabetic mice

This study was designed to evaluate the effect of ethanolic cherry sticks extract on the levels of glycoproteins in alloxan-induced diabetic mice. Forty-five adult male albino mice were divided equally into three groups: Group 1: control, Group 2: diabetic mice, Group 3: diabetic mice treated with cherry sticks extract as well as to eighteen mice treated with cherry sticks extract only for toxicity test. All treatments were administered via an intragastric tube. Diabetes was induced in the mice of Group 3 by an intraperitoneal injection with 100 mg/kg body weight of alloxan. Oral administration of cherry sticks extract at a concentration of 250 mg/kg body weight for 15 days significantly reduced the levels of blood glucose, glycosylated hemoglobin, urea, and creatinine as well as those of hexose, hexosamine, fucose, and sialic acid in the diabetic mice treated with the cherry sticks extract as compared to untreated diabetic mice, with no adverse effects in mice treated only with cherry sticks extract. In conclusion, cherry sticks extract proved to have a beneficial effect on the diabetic mice in this study. In light of these advantageous results, it is advisable to broaden the scale of use of cherry sticks extract in a trial to alleviate the adverse effects of diabetes.     

Protective Role of Artemisia Afra Aqueous Extract on Tissue Antioxidant Defense Systems in Streptozotocin-Induced Diabetic Rats

Changes in antioxidant capacity in the body as a result of oxidative stress play an important role in the development of diabetic complications. The aim of this study was to evaluate the effect of aqueous extract of Artemisia afra Jacq. ex Willd. on antioxidant defense systems in the liver and kidney of streptozotocin-induced diabetic rats. Administration of the extract to diabetic rats for 21 days significantly reduced blood glucose levels and increased body weight. The diabetic animals exhibited decreased levels of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced glutathione (GSH) in the liver and kidney, which were restored to near normal levels following treatment with the herb. The increased levels of lipid peroxidation observed in the tissues of diabetic rats were also reverted back to near normalcy after administering the extract. These findings revealed the protective role of A. afra on tissues by reducing oxidative stress which could be attributed to its flavonoids content. The efficacy of the plant compared favourably well with glibenclamide, a standard hypoglycemic drug.     

Pulmonary carcinogenesis induced by ferric nitrilotriacetate in mice and protection from it by Brazilian propolis and artepillin C

In experiments using the renal carcinogen ferric nitrilotriacetate (Fe-NTA) in male ddY mice, primary pulmonary cancers were also induced in bronchiolar and alveolar tissues. 4-Hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), products of oxidative processes, increased in bronchiolar and alveolar cells after administration of Fe-NTA. These substances disappeared after oral administration of propolis or artepillin C, as shown histochemically, and correlated with an anticancer prophylactic effect of propolis and artepillin C. From our investigation, lipid peroxidation seems to play an important role in pulmonary carcinogenesis. Malignant progression from adenoma of bronchiolar or alveolar origin to malignant tumors has been proposed to involve a stepwise transformation. In our study, adenomas developed into adenocarcinomas and large cell carcinomas after treatment with Fe-NTA. In contrast, after oral administration of propolis or artepillin C, adenomas did not progress to carcinomas. Instead of developing into large cell cancers, as induced by Fe-NTA in control mice, adenomas showed remarkable proliferation of macrophages and local anti-oxidant activity after treatment with either propolis or artepillin C. Propolis and artepillin C therefore appear to inhibit lipid peroxidation and the development of pulmonary cancers.     

Studies on the mechanism of alloxan-diabetes potentiation of carbon tetrachloride-induced liver necrosis.

Carbon tetrachloride (CCl4)-induced liver necrosis in alloxan diabetic rats is markedly more intense than in controls as established by determination of isocitric dehydrogenase activity in plasma or by histological techniques. The covalent binding (CB) of CCl4 reactive metabolites to liver microsomal lipids is higher in alloxan diabetic rats than in controls. Cytochrome c reductase activity remains unchanged in alloxan diabetic rats. All the alterations described above observed in the diabetic animals are reverted by insulin administration. CCl4-induced lipid peroxidation of microsomal lipids, in contrast, is equally intense in controls than in alloxan diabetic animals and it is not modified by insulin treatment. Body temperature in alloxan diabetic animals treated with CCl4 is lower than in controls treated with the hepatotoxin. Results suggest that part of the enhanced necrogenic response of the liver observed in alloxan diabetic rats is due to increased CB to liver cell constituents but available evidence from the present and another work suggest that increased susceptibility of the liver from alloxan diabetic animals play a major role in the potentiation of CCl4 deleterious effects.     

Trehalase activity in genetically diabetic mice (serum, kidney, and liver).

Trehalase activity was determined in serum, liver, and kidney in alloxan treated Swiss mice and in homozygous (Ob/Ob, Db/Db) and heterozygous (Ob/+, Db/m+) diabetic mice. Both alloxan and genetic diabetic mice exhibited a large increase in serum and liver trehalase activity with no change in kidney trehalase activity. The heterozygotes (Ob/+, Db/m+) showed only a slight increase of enzyme activity. Further quantitative differences were noticed between the genetic and alloxan diabetic animals. The liver enzyme activity increased from 10- to more than 20-fold in the liver of the homozygous Ob/Ob and Db/Db strains and only 3-fold (not significant compared to controls) in the alloxan treated animals. The above results suggest a regulatory relationship between the genes coding for trehalase and the enzymes of glucose metabolism activity involved in the development of the metabolic anomalies of diabetes. The structural gene for trehalase may well have survived elimination of selective pressure during phylogenesis and remained part of a co-regulated group of glucose metabolising enzymes. This could explain its sensitivity to mutations affecting glucose metabolism and its sensitivity to insulin directed regulatory mechanisms.     

Efficacy of ginseng drugs in experimental insulin-dependent diabetes and toxic hepatitis

Drugs obtained from the roots and leaves of plantation ginseng and ginseng root tissue culture displayed a high antidiabetic and hepatoprotective activity in experiments on mice and rats. In alloxan diabetes these adaptogenic phyto-agents prevented alloxan-induced activation of processes of lipid peroxidation in the pancreas and demonstrated definite insulinogenic properties: they increased the basal content of insulin in blood and the glucose-dependent secretion of this hormone. In CCl4 acute toxic hepatitis the studies ginseng drugs reduced the disorders of hepatic detoxification and glycogen-synthesizing functions.     

Antihyperglycemic and antioxidant activity of water extract from Anoectochilus roxburghii in experimental diabetes

The hypoglycemic and antioxidant effects of the water extract from Anoectochilus roxburghii in alloxan-induced diabetic mice were examined. Compared with untreated diabetic mice, the daily oral administration of the water extract from A. roxburghii at 0.5 or 2 g/kg for 14 days caused a significant decrease (p < .05) in blood glucose levels with similar effect but no evidence of dose-related effect. Simultaneously, the alteration in lipid metabolism was partially attenuated as evidenced by decreased serum total cholesterol and triglyceride levels and by increased high-density lipoprotein cholesterol concentration in diabetic mice (p < .05) but no dose-related effect was observed. In addition, the water extract from A. roxburghii caused a significant increase (p < .05) in the activities of enzymic antioxidants and the levels of vitamin E in liver and kidney of diabetic mice.Our results suggest that water extract from A. roxburghii possesses hypoglycemic and antioxidant properties after oral administration to mice showing alloxan-induced diabetes.     

Hesperidin protects renal and hepatic tissues against free radical-mediated oxidative stress during DMBA-induced experimental breast cancer

Hesperidin has been reported to have an excellent and wide variety of biological activities. This property has brought the compound to a new stage in the treatment of various oxidative stress-mediated diseases. The present investigation was aimed to evaluate the therapeutic potential of hesperidin by assaying the activities of antioxidant enzymes, lipid peroxidation, membrane bound marker enzymes, adenosine triphosphates, and TCA cycle enzymes, especially in kidney tissues during 7,12-dimethybenz(a)anthracene-induced breast cancer. Daily oral administration of hesperidin (30 mg/kg body wt) to breast cancer-bearing rats for 45 days demonstrated a significant (P < .05) decline in renal lipid peroxidation and membrane bound marker enzymes, as well as a remarkable increase in adenosine triphosphatases, mitochondrial functional enzymes, and renal antioxidants. Furthermore, histological studies of liver and kidney provided evidence of biochemical alterations. Thus, the protective effects of hesperidin on attenuating the peroxidation reaction and membrane bound marker enzyme activities as well as upregulation of adenosine triphosphatases, TCA cycle enzymes, and antioxidants suggest promising uses of flavonoglycoside hesperidin in the future treatment of oxidative stress-mediated diseases.     

Renal injury induced in alloxan diabetic rats. Role of Mycophenolate Mofetil as therapeutic agent

BackgroundRenal injury may develop in uncontrolled chronic hyperglycemia due to increased oxidative stress and release of pro-inflammatory mediators, leading to diabetic complications.MethodsMycophenolate Mofetil (MMF) is an immunosuppressant drug, an inhibitor of inosine monophosphate dehydrogenase (IMPDH), relevant to inflammation processes. MMF effect was tested in alloxan-diabetic rats on selected parameters like oxidative stress, gene expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1), in relation to microalbuminuria and renal function.ResultsWe found that the onset of microalbuminuria preceded the increase in serum glucose after alloxan treatment. Gene expression of TNF-α and TGF-β1 showed gradual increase after one and two weeks of alloxan administration as compared to the normal group. MMF administration decreased the gene expression of TNF-α and TGF-β1 in kidney tissues, serum glucose, fructosamine, urea, creatinine, C-reactive protein, malondialdehyde, urinary microalbumin and total protein. Histological examination of kidney tissues showed significant improvement in MMF treated rats as compared to diabetic control.ConclusionsMMF modulated renal injury of alloxan diabetic rats. Collective data may support its therapeutic effect but further clinical trials may be requested.     

Hypolipidemic Activities of Ficus Racemosa Linn. Bark in Alloxan Induced Diabetic Rats

Ficus racemosa (Moraceae family) is used in traditional system of medicine for the treatment of several disorders including diabetes mellitus. The aim of the study was to investigate the antihyperglycemic and hypolipidemic activities of ethanolic extract of Ficus racemosa bark (FrEBet) in alloxan-induced diabetic rats. A total number of 30 animals were divided into 5 groups of six each. Diabetes mellitus was induced by single intraperitoneal injection of freshly prepared solution of alloxan monohydrate (150 mg/kg bw) dissolved in physiological saline in overnight fasted wistar rats. Dose dependent studies for FrEBet (100–500mg/kg bw) was carried out to find out the effective pharmacological dose (antidiabetic and hypolipidemic) to alloxan-induced diabetic rats. Blood glucose, plasma insulin, total cholesterol, phospholipids, triglycerides, free fatty acids, HDL cholesterol and LDL cholesterol levels in plasma, erythrocyte membranes, liver and kidney were determined by specific colorimetric methods. An increase in blood glucose was accompanied by an increase in total cholesterol, phospholipids, triglycerides, FFA and decrease in HDL choleterol in diabetic rats. Oral administration of FrEBet (300mg/kg bw) to diabetic rats restrored the status of blood glucose, lipids and lipoproteins to near normal range. Our investigation thus shows that FrEBet has potent antidiabetic and hypolipidemic effects in alloxan-induced diabetic rats and these effects were much comparable to that of the standard reference drug, glibenclamide.     

Evaluation of anti-oxidative effects of propofol in experimental diabetes

This study was designed to evaluate the serum oxidative status during general anaesthesia established with propofol in alloxan-induced diabetic mice. Sixty mice were randomly allocated into two equal groups. The mice in the diabetic group were injected intraperitoneally with alloxan. Diabetic and normal mice were further divided into five treatment groups of six mice per group. The control group consisted of no treatment whilst the experimental groups received one to four doses of propofol (100?mg/kg BW) at 60-min intervals. In each group, trunk blood samples were collected 30?min after the last injection for the measurement of serum glucose, malondialdehyde (MDA) concentrations, and superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities. Propofol reduced circulating MDA levels and increased serum GPX activity in both alloxan-treated and normal mice. Propofol had no effect on serum glucose concentration. Propofol's increasing effect on GPX activity was significantly greater in alloxan-treated mice (90.27% within 60?min, 131.58% within 120?min, and 77.04% within 180?min) compared to normal mice. Serum SOD activity was significantly higher during exposure to propofol (61% within 180?min) in diabetic mice but was not statistically altered during exposure to propofol over time in normal mice. The results of this study demonstrate ameliorative effects of propofol on oxidative status in an alloxan-induced model of diabetes in mice.     

The effect of alloxan, and alloxan-induced diabetes on the kidney

Alloxan is known to induce diabetic renal changes as well as causing nephrotoxic alterations. However, no ultrastructural study has been performed to differentiate diabetic verses toxic affects of alloxan to the tubule and/or glomerulus. Therefore the present study used the "protected" kidney model to prevent one kidney from being exposed to the alloxan while allowing the other to receive the drug immediately. In all experimental animals the right renal hilum was gently occluded for 5 minutes and then released. This was performed prior to the injection of alloxan. Subsequently, the left renal hilum was occluded at the time of, and for 5 minutes after, alloxan administration (40 mg/kg i.v.). The experimental rats were divided into three groups: untreated diabetics, diabetics treated with protamine-zinc-insulin, and alloxan-treated rats that failed to become diabetic. Three groups of controls were included: one group received an equal volume of saline diluent as the experimental rats but no clamping of either renal hilum; another group received the saline and had the left renal hilum occluded for 5 minutes; and a third group had both the right and left renal hila occluded. All animals were followed and sacrificed after 9 weeks. Endogenous creatinine clearance did not change among groups. Alloxan-treated nondiabetic rats displayed marked interstitial nephritis in unprotected kidneys, while protected kidneys were normal. The diabetic state resulted in mesangial proliferation and focal glomerular basement membrane thickening as well as glomerular capillary endothelial abnormalities and visceral epithelial foot-process fusion. The endothelial changes consisted of focal areas showing a reduction in the size of endothelial fenestrae. All glomerular changes were ameliorated by insulin treatment. We conclude: 1) alloxan per se is distinctly nephrotoxic; and 2) the glomerular endothelium and epithelium are involved early in the course of experimental diabetes.     

The effect of alloxan-induced diabetes on triamine lesions in the ventromedial hypothalamus.

It has been demonstrated that the ventromedial hypothalamus (VMH) of alloxan-induced diabetic mice is protected from subsequent gold thioglucose (GTG)-induced lesions. Another compound, 3,3'-methyliminobis-(N-methylpropylamine) (MIMPA), a triamine structurally unrelated to GTG, has been shown to cause similar VMH lesions in mice. We chose to investigate the effect of alloxan-induced diabetes on VMH lesion formation in MIMPA-treated mice. In this study CF-1 female mice were made diabetic by a simple intravenous (IV) injection of alloxan and subsequently treated with MIMPA by subcutaneous injection (SC). Contrary to studies which showed that GTG-induced VMH lesions are insulin dependent, an insulin deficiency did not inhibit MIMPA-induced lesions in the VMH of mice. Our data suggests, albeit GTG is suspected to induce VMH necrosis by attaching to glucoreceptors and insulin-sensitive neurons, MIMPA works by a different and as yet unknown mechanism. We conclude that MIMPA-induced lesions in the VMH of mice are not insulin dependent.     

Lipid peroxidation and HSP72/73 expression in rat following cadmium chloride administration: Interactions of magnesium supplementation

Objective: to determine whether magnesium (Mg) supplementation could have a protective effect against the cadmium (Cd)-induced oxidative stress in liver, kidneys and testes of adult male rats. Stress was evaluated by measuring lipid peroxidation by thiobarbituric acid reactive substances (TBARS) and the heat shock protein (HSP) 72/73 expression.

CdCl₂ injections (2.5 mg/day/kg body weight) for 10 days resulted in a time dependent increase of Cd accumulation in liver, kidney and testes, the highest levels being found in liver (400 μg/g dried tissue). At the same time, an increase of lipid peroxidation was observed. The effect was maximal at day 1 of Cd treatment in liver and testes, and later (day 5) in kidney. Then, Cd-induced lipid peroxidation decreased, suggesting the activation of antioxidant defense mechanisms.

Injections of Mg SO₄ (300–600 mg/day/kg body weight) reduced in a dose-dependent manner Cd-induced lipid peroxidation in liver and kidney as well as the accumulation of Cd in liver, kidney and testes. In testes, a protective effect of Mg was found only during the early phase of Cd-poisoning. On days 5 and 10, lipid peroxidation was even increased as compared to controls.

In liver and testes only the constitutive HSP73 was detected whereas in kidney both HSP73 and the inducible HSP72 were expressed. HSP72/73 expression was not significantly increased by Cd and HSP73 was even lowered in kidney, probably due to the strong dose used. These results were not modified by Mg injections.

Conclusion: Mg supplementation can reduce Cd accumulation in organs and lipid peroxidation related to Cd administration.     

Sida rhomboidea.Roxb extract alleviates pathophysiological changes in experimental in vivo and in vitro models of high fat diet/fatty acid induced non-alcoholic steatohepatitis

The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities.