Abstract
BackgroundOxidative stress could play a role in pathogenesis of hepatitis C virus (HCV) infection. The aim of our study is to determine oxidant/antioxidant status of patients with chronic hepatitis C (CHC), and the effect of pegylated interferon alfa-2b plus ribavirin combination therapy on oxidative stress.MethodsNineteen patients with chronic HCV infection and 28 healthy controls were included in the study. In control and patient groups, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, erythrocyte malondialdehyde (MDA) levels, erythrocyte CuZn-superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GSH-Px) activities were measured. After pegylated interferon alfa-2b and ribavirin combination therapy for 48 weeks, these parameters were measured again in the patient group.ResultsSerum MDA levels increased significantly in CHC patients (n:19), before the treatment when compared with healthy subjects (n:28) 9.28 ± 1.61, 4.20 ± 1.47 nmol/ml, p < 0.001 respectively. MDA concentration decreased significantly (p < 0.001) after the treatment as well as ALT, AST activity, in erythrocytes of these patients. Average antioxidant enzymes (superoxide dismutase and glutathione peroxidase) were significantly lower in erythrocytes of patients with CHC before treatment compared with the control group (both, p < 0.001). Chronic Hepatitis C patients after pegylated interferon alfa-2b and ribavirin therapy showed values of SOD, GSH-Px were significantly higher than pretreatment levels (both, p < 0.001).ConclusionOur results show that patients with chronic HCV infection are under the influence of oxidative stress associated with lower levels of antioxidant enzymes. These impairments return to level of healthy controls after pegylated interferon alfa-2b plus ribavirin combination therapy of CHC patients. Although interferon and ribavirin are not antioxidants, their antiviral capacity might reduce viral load, and inflammation, and perhaps through this mechanism might reduce virus-induced oxidative stress.
Highlights
Oxidative stress could play a role in pathogenesis of hepatitis C virus (HCV) infection
The results obtained show that the serum MDA is significantly increased in selected group of chronic hepatitis C (CHC) patients (n:19), before pegylated interferon alfa-2b, and ribavirin treatment when compared with healthy subjects (n:28) [(9.28 ± 1.61 vs. 4.20 ± 1.47 nmol/ml, p < 0.001)] Table 1
These results show that the patients with CHC are under the influence of increased oxidative stress
Summary
Oxidative stress could play a role in pathogenesis of hepatitis C virus (HCV) infection. Different mechanisms including immunological liver damage, direct cytotoxicity mediated by different viral product and inductions of oxidative stress have been suggested as playing a pathogenic role in this infection [1]. Several lines of evidence support this contention, including the existence of activated glutathione turnover, the presence of increased levels of lipid peroxidation products and augmented iron stores in the liver, and the finding of diminished reduced glutathione values in peripheral blood mononuclear cells and erythrocytes. It has been showed that patients with chronic hepatitis C exhibit an increased production of tumor necrosis factor-alfa (TNF-α), a cytokine that can produce oxidative stress by simulating the generation of reactive oxygen species (ROS) such as superoxide ion (O2.) and hydrogen peroxide (H2O2). In the presence of metals (such as Fe 3+), O2.- can react with H2O2 to generate a hydroxyl radical than become even more reactive and cytototoxic than O2.- or H2O2 [2]
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