Oxidative Stress-induced Liver Damage Research Articles

Deoxynivalenol and T-2 toxin cause liver damage and egg quality degradation through endoplasmic reticulum stress in summer laying hens.

The present study aimed to find whether low doses of mixed mycotoxins would affect egg quality in laying hens, and to explore the oxidative stress induced liver damage through endoplasmic reticulum during summer stress. A total of 96 Jinghong laying hens, 36 wks of age, were divided into four treatments, with eight repetitions per treatment and three hens per repetition. All the hens were raised in summer (average temperature: 31.3 ± 0.5℃; average humidity: 85.5 ± 0.2%) for 28d. One treatment was fed a basal diet as control (CON), and the other three treatments were fed the same diets containing 3.0mg/kg deoxynivalenol (DON), 0.5mg/kg T-2 toxin (T-2), and 1.5mg/kg DON + 0.25mg/kg T-2 toxin (Mix). Albumen height and Haugh unit were decreased (P < 0.05) in the Mix group on day 14 and 28. The activity of total antioxidant capacity, glutathione peroxidase, catalase, and superoxide dismutase were decreased (P < 0.05) in the DON, T-2, and Mix groups. The alkaline phosphatase level in DON, T-2, and Mix groups was significantly increased (P < 0.05). The level of interleukin-1β, interferon-γ, and tumor necrosis factor-α in the Mix group were higher (P < 0.05) than CON, DON, and T-2 groups. Mix group upregulated the mRNA expressions of protein kinase RNA-like ER kinase, activating transcription factor4, IL-1β, nuclear factor-κ-gene binding, and nuclear respiratory factor 2 in the liver (P < 0.05). The results showed that low doses of DON and T-2 toxin could cause oxidative stress in the liver, but DON and T-2 toxin have a cumulative effect on virulence, which can reduce egg quality and cause endoplasmic reticulum stress in the liver.

Water extract of lotus leaves has hepatoprotective activity by enhancing Nrf2- and epigenetics-mediated cellular antioxidant capacity in mouse hepatocytes

• The main phenolics in LL-WE were EGCG, rutin, gallic acid, myricetin, quercetin, ellagic acid, etc. • LL-WE reduced the damage of mouse AML-12 hepatocytes caused by APAP-induced oxidative stress. • LL-WE promoted glutathione synthesis and activated the Nrf2 pathway. • LL-WE upregulated Nrf2-mediated antioxidant enzymes and downregulated HDACs and DNMTs. • LL-WE inhibited the in vitro activity of CpG methyltransferase (M.SssI). The liver is an important organ in the human body; however, studies have shown that the excessive intake of acetaminophen (APAP), the primary ingredient in marketing pain relievers, may cause oxidative damage to liver cells. Here we found that lotus leaf water extract (LL-WE) enriched with various phenolic compounds can prevent mice AML-12 hepatocytes from APAP-induced injury, and trigger the Nrf2 pathway in HepG2-C8 cells with ARE-luciferase plasmid. LL-WE effectively induced Nrf2 nuclear translocation and glutathione synthesis, increased gene expression of antioxidant enzymes (HO-1, NQO1, and UGT1A), and reduced protein levels of epigenetic modification enzymes (HDACs and DNMTs) in AML-12 cells. LL-WE also inhibited the activity of M.SssI CpG methyltransferase in vitro . These results suggest that LL-WE can be a potential hepatoprotective agent to reduce oxidative stress-induced liver damage by activating the Nrf2 pathway and downregulating epigenetic modification enzymes.

Protective Effects of A. sativa against Oxidative Stress-Induced Liver Damage in Ovariectomized Mice

Postmenopausal women express great failure in their ovarian hormone production, especially estrogen. This deficiency may promote hypercholesterolemia and accelerate the redox imbalance. The present study was designed to evaluate the protective effect of Avena sativa against estrogen deficiency-induced liver and uterus oxidative injury in experimental ovariectomized mice. Female mice were randomly divided into five groups: group one (negative control) received normal diet and distilled water (C), group two (positive control) received daily enriched diet with oat grains and was kept on tap distilled water at a dose of 200 mg kg−1 d−1 (A), group three (ovariectomized mice) was nontreated fed with normal diet (O), group four includes ovariectomized mice treated daily with estradiol given by intraperitoneal injection at a dose of 100 μg kg−1 d−1 (OE), and the fifth group also includes ovariectomized mice which received enriched diet with oat grain parts with the same dose given to group two. The treatment period lasted two consecutive months. Both oat and hormonal treatments of ovariectomized groups resulted in a significant reduction in triglycerides and total cholesterol and increased high-density lipoprotein (HDL) levels in the plasma after 21 and 60 days of treatment. Besides, the coadministration of A. sativa has decreased the activities of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) and increased transaminase activities after 21 and 60 days of treatment. On the other hand, this cereal has restored the enzymatic (SOD, CAT, and GPx) and nonenzymatic antioxidant activities (GSH) as well as the elevated thiobarbituric acid reactive substances (AOPP and PCO) to near-normal values. The beneficial effects of this cereal were confirmed by a histological study of the liver and uterus of all previous cited groups. Our finding emphasized the antioxidant and antilipidemic effect of oat grain part, suggesting the use of this cereal in the prevention of liver and uterus diseases that occurred in postmenopausal women.

Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies.

Circadian rhythms and clock gene expressions are regulated by the suprachiasmatic nucleus in the hypothalamus, and melatonin is produced in the pineal gland. Although the brain detects the light through retinas and regulates rhythms and melatonin secretion throughout the body, the liver has independent circadian rhythms and expressions as well as melatonin production. Previous studies indicate the association between circadian rhythms with various liver diseases, and disruption of rhythms or clock gene expression may promote liver steatosis, inflammation, or cancer development. It is well known that melatonin has strong antioxidant effects. Alcohol drinking or excess fatty acid accumulation produces reactive oxygen species and oxidative stress in the liver leading to liver injuries. Melatonin administration protects these oxidative stress-induced liver damage and improves liver conditions. Recent studies have demonstrated that melatonin administration is not limited to antioxidant effects and it has various other effects contributing to the management of liver conditions. Accumulating evidence suggests that restoring circadian rhythms or expressions as well as melatonin supplementation may be promising therapeutic strategies for liver diseases. This review summarizes recent findings for the functional roles and therapeutic potentials of circadian rhythms and melatonin in liver diseases.

Hepatoprotective efficacy of Shanxi aged vinegar extract against oxidative damage in vitro and in vivo

• SAVE exhibited hepatoprotective effects in vitro and in vivo . • SAVE protected against liver oxidative damage. • SAVE activated Nrf2-dependent antioxidant defences. Shanxi aged vinegar, a traditional fermented food, has beneficial effects on human health. Shanxi aged vinegar extract (SAVE) is rich in antioxidant components, which can prevent free radical-induced diseases. In the present study, we investigated the protective effects and molecular mechanisms of SAVE on oxidative stress-induced liver damage in vitro and in vivo . The results showed that SAVE attenuated H 2 O 2 -induced cytotoxicity and exhibited protective activity in hepatocyte by inhibiting reactive oxygen species (ROS) generation and cell apoptosis. In addition, SAVE alleviated CCl 4 -induced liver damage in mice through inhibiting cytochrome P450 2E1 (CYP2E1) expression, ROS generation and production of malondialdehyde (MDA), 4-hydroxyalkenals (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Moreover, SAVE protected against oxidative stress-induced liver damage by elevating antioxidant enzymes activities and glutathione level and upregulating Nrf2-antioxidant response element (ARE) pathway. The findings suggest that SAVE exhibits hepatoprotective effect and could be a potential alternative for hepatic oxidative damage.

Antioxidative, anti-inflammatory and hepatoprotective effects of resveratrol on oxidative stress-induced liver damage in tilapia (Oreochromis niloticus)

Resveratrol, a dietary polyphenol, has been shown to exert antioxidation, hepatoprotection, anti-inflammation and immunostimulation. However, the effects and underlying mechanism of resveratrol on liver injury in fish are still unclear. In the present study, we investigated the potential protective effects and mechanism of resveratrol on oxidative stress-induced liver damage in tilapia. Fish were fed diet containing four doses of resveratrol (0, 0.1, 0.3, and 0.6 g/kg diet) for 60 days, and then given an intraperitoneal injection of H2O2 or saline. The results showed that administration of resveratrol significantly ameliorated H2O2-induced liver injury. In serum and liver, resveratrol treatment suppressed the oxidative stress, as evidenced by the decline of lipid peroxidation level and increase of antioxidant activity. Resveratrol also activated erythroid 2-related factor 2 (Nrf2) signaling pathway and enhanced the heme oxygenase 1 (HO-1), NAD(P) H:quinone oxidoreductase 1 (NQO-1), glutathione S-transferase (GST) mRNA levels. Meanwhile, resveratrol treatment repressed TLR2-Myd88-NF-κB signaling pathway to decrease the inflammatory response in H2O2-induced liver injury as evidenced by the lower interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-8 mRNA levels and higher IL-10 mRNA level. Moreover, resveratrol treatment attenuated immunotoxicity in liver of H2O2-treated fish, accompanied by upregulation of hepcidin (HEP), complement 3 (C3) and lysozyme (LZM) mRNA levels. Overall results suggested that the protection of resveratrol on H2O2-induced liver injury, inflammation and immunotoxicity was due to its antioxidant property and its ability to modulate the Nrf2 and TLR2-Myd88-NF-κB signaling pathways.

Hepatoprotective effect of 2′-O-galloylhyperin against oxidative stress-induced liver damage through induction of Nrf2/ARE-mediated antioxidant pathway

2′-O-galloylhyperin (2′-O-GH), an active compound isolated from Pyrola calliantha, possesses remarkable antioxidant activity. The aims of this study were to investigate the hepatoprotective effect of 2′-O-GH against oxidative stress and elucidate the underlying mechanistic signaling pathways in HepG2 cells as well as in an animal model. Results showed that 2′-O-GH significantly inhibited hydrogen peroxide (H2O2)-induced HepG2 cell death in a dose dependent manner. The mitogen-activated protein kinase activation, ROS production, mitochondrial membrane potential, intracellular calcium level and subsequent apoptotic protein activation in H2O2-stimulated HepG2 cells were remarkably inhibited by 2′-O-GH. Furthermore, 2′-O-GH stimulation resulted in a fast and dramatic activation of Akt and nuclear translocation of the NF-E2-related factor 2 (Nrf2), along with the increased expression of heme oxygenase-1 (HO-1) and levels of glutathione (GSH). Meanwhile, histopathological evaluation of the liver also revealed that 2′-O-GH effectively ameliorated CCl4-induced the hepatic damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Therefore, these results suggested the hepatoprotective effect of 2′-O-GH might be correlated with its antioxidant and free radical scavenger effect.

Aberrant GSTP1 promoter methylation predicts short‐term prognosis in acute‐on‐chronic hepatitis B liver failure

Glutathione-S-transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute-on-chronic hepatitis B liver failure (ACHBLF). To evaluate the methylation level of GSTP1 promoter in acute-on-chronic hepatitis B liver failure and determine its predictive value for prognosis. One hundred and five patients with acute-on-chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained. GSTP1 methylation levels were significantly higher in patients with acute-on-chronic hepatitis B liver failure (median 16.84%, interquartile range 1.83-59.05%) than those with CHB (median 1.25%, interquartile range 0.48-2.47%; P < 0.01) and HC (median 0.80%, interquartile range 0.67-1.27%; P < 0.01). In acute-on-chronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P < 0.05) than survivors. GSTP1 methylation level was significantly correlated with total bilirubin (r = 0.29, P < 0.01), prothrombin time activity (r = -0.24, P = 0.01) and model for end-stage liver disease (MELD) score (r = 0.26, P = 0.01). When used to predict 1- or 2-month mortality of acute-on-chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P < 0.01; AUC 0.83 vs. 0.70, P < 0.05 respectively]. Meanwhile, patients with GSTP1 methylation levels above the cut-off points showed significantly poorer survival than those below (P < 0.05). Aberrant GSTP1 promoter methylation exists in acute-on-chronic hepatitis B liver failure and shows high predictive value for short-term mortality. It might serve as a potential prognostic marker for acute-on-chronic hepatitis B liver failure.

Evaluation of Antioxidant Activity of Giant African Snail (Achachatina maginata) Haemolymph in CCl4- Induced Hepatotoxixity in Albino Rats

Objective: To evaluate the acute toxicity, in vitro antioxidant and hepatoprotective activities of Giant African Snail (Achachatina maginata) haemolymph against carbon tetrachloride (CCl4) induced liver damage in albino rats.Place and Duration of Study: Department of Biochemistry, Federal University of Technology, Minna, Nigeria. It was carried out between September and December, 2014.Methods: Antioxidant activity of the haemolymph was assayed by DPPH radical scavenging, reducing properties, and inhibition of lipid peroxidation by the haemolymph. In addition, the phenol and flavonoid contents were also evaluated. The safety of the extract was also investigated by the acute oral toxicity limit test. The hepatoprotective activities of the haemolymph were compared with a known hepatoprotective drug, silymarin. For this purpose, twenty adult albino rats were assigned into 5 groups. Group 1 and 2 serves as normal control and CCL4 control respectively. Group 3-5 were treated with 200 mg/kg, 400 mg/kg haemolymph and 100 mg/kg Silymarin respectively.Results: The lethal dose (LD50) of haemolymph determined was greater than 5000 mg /kg in rats. The amount of total phenolics and flavonoids were estimated to be 9.30±0.11 mg/g GAE and 15.20±0.59 mg/g catechin equivalent respectively. The haemolymph exhibited concentration dependent in vitro antioxidant activity with an IC50 value of 579.66±2.69 μg/mL in the DPPH radical scavenging activity and 310.75±3.12 μg/mL in lipid peroxidation inhibitory activity but shows low reducing properties compare to ascorbic acid. The liver damage was evidenced by the elevated levels of serum and liver ALT, ALP, serum AST, hepatic thio-barbituric acid reacting substances (TBARS) and reduced serum catalase in CCl4-hepatotoxic rats. Administration of haemolymph (200/400 mg/kg) and standard control drug silymarin (100 mg/kg) significantly (P<0.05) reduced CCL4- induced elevations of the levels of AST, ALT, ALP, and TBARS while the reduced concentration of catalase due to CCL4 was reversed. However, the SOD activities was significantly (P<0.05) higher in CCL4 treated group compare to the control group.Conclusion: The present study proved the antioxidant activity of Giant African Snail (Achachatina maginata) haemolymph can be used as accessible source of natural antioxidants with potential application to reduce oxidative stress induced liver damage.

Allopurinol Ameliorates Thioacetamide-Induced Acute Liver Failure by Regulating Cellular Redox-Sensitive Transcription Factors in Rats

Oxidative stress plays important role in the development of acute liver failure. In this study, we investigated effects of allopurinol (AP) upon thioacetamide (TAA)-induced liver injury and the potential mechanisms leading to amelioration in inflammation with AP treatment. Acute liver failure was induced by intraperitoneal administration of TAA (300 mg/kg/day for 2 days). Thirty-five rats were divided into five groups as control (group 1), TAA (group 2), TAA + 25AP (group 3), TAA + 50 AP (group 4), and TAA + 100AP (group 5). The number of animals in each group was seven. At the end of the study, histopathological, biochemical, and western blot analysis were done. TAA treatment significantly increased serum levels of aminotransferases, liver malondialdehyde (MDA), nuclear factor-kappa B (NF-қB ), activator protein-1 (AP-1), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels, and the necro-inflammation scores. Nevertheless, nuclear factor E2-related factor-2 and heme oxygenase-1 (HO-1) expressions in the liver were decreased by TAA. AP treatment significantly lowered the serum levels of aminotransferases (P < 0.01) and liver MDA, NF-κB, AP-1, TNF-α, COX-2, and IL-6 expressions (P < 0.05). Moreover, AP restored the liver Nrf2 and HO-1 expressions and improved the necro-inflammation scores significantly. AP improves oxidative stress-induced liver damage by regulating cellular redox-sensitive transcriptor factors and expression of pro-inflammatory and antioxidant defense mechanisms. AP probably exerts these beneficiary features by its free radical scavenging ability in a dose-dependent manner.

Acute Exposure of Apigenin Induces Hepatotoxicity in Swiss Mice

Apigenin, a dietary flavonoid, is reported to have several therapeutic effects in different diseases including cancer. Toxicity of Apigenin is however, least explored, and reports are scanty in literature. This warrants dose-specific evaluation of toxicity in vivo. In the present study, Apigenin was administered intraperitoneally to Swiss mice at doses of 25, 50, 100 and 200 mg/kg. Serum levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP) were measured along with the examination of liver histology, reactive oxygen species (ROS) in blood, lipid peroxidation (LPO), glutathione level, superoxide dismutase activity, catalase activity, glutathione S-transferase activity and gene expression in liver tissue. Increase in ALT, AST, ALP, ROS, ratio of oxidized to reduced glutathione (GSSG/GSH) and LPO, altered enzyme activities along with damaged histoarchitecture in the liver of 100 or 200 mg/kg Apigenin treated animals were found. Microarray analysis revealed the differential expression of genes that correspond to different biologically relevant pathways including oxidative stress and apoptosis. In conclusion, these results suggested the oxidative stress induced liver damage which may be due to the regulation of multiple genes by Apigenin at higher doses in Swiss mice.

Isolation and identification of compound from dropwort (Oenanthe javanica) with protective potential against oxidative stress in HepG2 cells

The protective effect of dropwort (Oenanthe javanica) was investigated in HepG2 cells under oxidative stress, and its active compound was identified. Compared to H2O2-alone treated cells, a drastic increase (35%) in protective activity was observed in the cells pretreated with 80% ethanol extract (OJE) of dropwort, suggesting that OJE possessed a potent hepatoprotectant. After a sequential procedure consisting of solvent-partitioning chromatography, TLC, and HPLC was conducted, the compound with proven hepatoprotective activity from OJE was isolated and identified as caffeic acid. Results indicated that caffeic acid in dropwort contributed to this herb’s protective profile against oxidative stress-induced liver damage.

Changes induced by a fructose-rich diet on hepatic metabolism and the antioxidant system

Aims The effect of a three-week fructose-rich diet (FRD) upon gene expression, protein and activity levels of liver antioxidant system and carbohydrate metabolism was studied. Main methods Serum glucose (fasting and after a glucose load), triglyceride and insulin levels of normal male Wistar rats were measured. In liver, we measured gene/protein expression and enzyme activity of catalase (CAT), copper–zinc–superoxide dismutase (CuZnSOD) and glutathione peroxidase (GSHPx); reduced glutathione (GSH); protein carbonyl content; thiobarbituric acid reactive substances (TBARS) content and microsomal membrane susceptibility to lipid peroxidation; glucokinase (GK), glucose-6-phosphatase (G-6-Pase) and glucose-6-phosphate dehydrogenase (G-6-PDH) activity; and glycogen, pyruvate, lactate and triglyceride content. Key findings Similar body weights and caloric intake were recorded in both groups. FRD rats had higher serum glucose, insulin and triglyceride levels, molar insulin:glucose ratio, HOMA-IR values and impaired glucose tolerance, whereas CAT, CuZnSOD and GSHPx relative gene expression levels were significantly lower. CAT and CuZnSOD protein expression, CAT activity and GSH content were also lower, while protein carbonyl content was higher. No differences were recorded in CuZnSOD, MnSOD and GSHPx activity, TBARS content and membrane susceptibility to lipid peroxidation. Glycogen, lactate and triglyceride content and GK, G-6-Pase and G-6-PDH activity were significantly higher in FRD rats. Significance In the presence of oxidative stress, the liver exhibits changes in the carbohydrate and lipid metabolic pathways that would decrease reactive oxygen species production and their deleterious effect, thus inducing little impact on specific antioxidant mechanisms. This knowledge could facilitate the design and implementation of strategies to prevent oxidative stress-induced liver damage.

Attenuation of oxidative stress and alteration of hepatic tissue ultrastructure by D-pinitol in streptozotocin-induced diabetic rats

The present study was aimed to investigate the effect of D-pinitol on hyperglycaemia mediated oxidative stress by analysing the hepatic antioxidant competence, pro-inflammatory cytokines and ultrastructural changes in liver tissues of streptozotocin-induced diabetic rats. Oral administration of D-pinitol (50 mg/kg b.w.) resulted in significant (p < 0.05) attenuation in blood glucose, glycosylated haemoglobin and pro-inflammatory markers such as TNF-α, IL-1β, IL-6, NF-κB p65 unit and NO and significant (p < 0.05) elevation in the plasma insulin level. In addition, D-pinitol instigated a significant escalation in the levels of hepatic tissue non-enzymatic antioxidants and the activities enzymatic antioxidants of diabetic rats with significant (p < 0.05) decrease in lipid peroxides and hydroperoxides formation, thus demonstrating the protective role of D-pinitol on the hepatic tissues from oxidative stress-induced liver damage. These biochemical observations were complemented by histological and ultrastructural examination of liver section. Thus, the present study demonstrates the hepatoprotective nature of D-pinitol by attenuating hyperglycaemia-mediated pro-inflammatory cytokines and oxidative stress.

Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis

In our previous work, including analysis of more than 10,000 sera from control patients and patients with a variety of liver diseases, we have demonstrated that with the use of recombinant autoantigens, antimitochondrial autoantibodies (AMAs) are only found in primary biliary cirrhosis (PBC) and that a positive AMA is virtually pathognomonic of either PBC or future development of PBC. Although the mechanisms leading to the generation of AMA are enigmatic, we have postulated that xenobiotic-induced and/or oxidative modification of mitochondrial autoantigens is a critical step leading to loss of tolerance. This thesis suggests that a severe liver oxidant injury would lead to AMA production. We analyzed 217 serum samples from 69 patients with acute liver failure (ALF) collected up to 24 months post-ALF, compared with controls, for titer and reactivity with the E2 subunits of pyruvate dehydrogenase, branched chain 2-oxo-acid dehydrogenase, and 2-oxo-glutarate dehydrogenase. AMAs were detected in 28/69 (40.6%) ALF patients with reactivity found against all of the major mitochondrial autoantigens. In addition, and as further controls, sera were analyzed for autoantibodies to gp210, Sp100, centromere, chromatin, soluble liver antigen, tissue transglutaminase, and deaminated gliadin peptides; the most frequently detected nonmitochondrial autoantibody was against tissue transglutaminase (57.1% of ALF patients). The strikingly high frequency of AMAs in ALF supports the thesis that oxidative stress-induced liver damage may lead to AMA induction. The rapid disappearance of AMAs in these patients provides further support for the contention that PBC pathogenesis requires additional factors, including genetic susceptibility.

Effect of Vitamin E on Serum Aminotransferase and Thioredoxin Levels in Patients with Viral Hepatitis C

Objectives: Oxidative stress induces cellular responses such as cell death, gene activation and cell proliferation, in the liver. Vitamin E (Vit. E) has been found to protect the liver against oxidative stress in animal experiments. Thioredoxin (TRX) is a stress inducible, multifunctional protein, secreted during oxidative stress. This study evaluated effects of Vit. E on serum TRX and aminotransferase levels in hepatitis C virus (HCV) patients, partly non-responsive to initial interferon (IFN), with higher than average level of serum alanine aminotransferase (ALT) after receiving anti-inflammatory drug treatment. Methods: Seventeen HCV patients (male=3; female=14) of age 62±7.65 years receiving anti-inflammatory drug therapy, at least 6 months prior to Vit. E administration, were given d-α´-tocopherol 500 mg/day, orally, for a period of 3 months. ALT, aspartate aminotransferase (AST), TRX and Vit. E were measured at 0, 1, 2 and 3 months and 1 month after end of treatment. As controls, the same patients biochemical data, 3 months from the start of therapy were used. Patients were divided into three categories: total patients “T”, low ALT group “L” (ALT<70 IU/l) and high ALT group “H”(ALT>70 IU/l), respectively.Results: The ALT level was lowered, significantly in group H, in the 1st, 2nd, 3rd and 1-month post therapy, compared to the initial value. But group L showed little or no change in ALT. Post Vit. E therapy, in groups T and H, the TRX level was elevated but remained below initial levels, whereas in group L, TRX level remained significantly lower than the pretreatment value. Groups T and L, showed significant reduction (p<0.05) in serum TRX levels in the 2nd and 3rd month. Group H showed a tendency towards TRX reduction, but not significantly. Serum Vit. E levels increased significantly (p<0.0001) from the 1st to 3rd month in all three T, H and L groups. Conclusion: Oxidative stress induced liver damage is reduced by Vit. E in patients with viral hepatitis C, particularly those with initial ALT levels >70 IU/l. Vit. E treatment causes reduction of oxidative stress markers as TRX and ALT in sera. Therefore, Vit. E can act as a supportive therapy to combat liver damage caused by oxidative stress, in such patients with continuously high levels of ALT even after anti-viral and anti-inflammatory drug therapy.