Superoxide Dismutase in Patients With Chronic Hepatitis C Virus Infection

Abstract

Abstract-It has been reported that hepatitis C virus (HCV) may cause oxidative stress in infected cells. Patients with chronic hepatitis C exhibit an increased production of tumor necrosis factor-␣ (TNF␣), a cytokine that can produce oxidative stress by stimulating the generation of reactive oxygen species (ROS). Cell defense against ROS includes overexpression of Mn-superoxide dismutase (SOD), an inducible mitochondrial enzyme. To investigate cell defense against oxidative stress in HCV infection, we analyzed Mn-SOD mRNA in liver and in peripheral blood mononuclear cells (PBMC) from patients with chronic hepatitis C. Mn-SOD expression in PBMC was significantly increased in patients with HCV infection. Patients with sustained virological and biochemical response after therapy showed significantly lower Mn-SOD than patients with positive viremia. By contrast, Mn-SOD expression was not enhanced in the liver of patients with chronic hepatitis C. The values of Mn-SOD mRNA did not correlate with TNF␣ mRNA expression, viral load, or liver disease activity. Our results indicate that in HCV infection an induction of Mn-SOD was present in PBMC but absent in the liver, suggesting that this organ could be less protected against oxidative damage. Oxidative stress could participate in the pathogenesis of HCV infection.

Antioxidant status and glutathione metabolism in peripheral blood mononuclear cells from patients with chronic hepatitis C

“…Increased SOD activity appears to be an adaptive response to increased generation of superoxide ions (29). Thus, our findings support the existence of oxidative stress in PBMC from patients with chronic HCV infection and are in agreement with previous data from our group showing increased Mn-SOD mRNA values in PBMC from these patients (16).…”

“…In addition to inflammatory mediators, oxidative stress can also be produced as a direct consequence of viral replication. In this respect it should be considered that HCV infects not only hepatocytes but also lymphocytes and monocytes (14,16,34), and thus it can cause direct cytopathic effects in the liver as well as in lymphoid cells.…”

“…HCV detection, quantitation and genotyping were performed as previously described (16,19). Histological evidence of chronic hepatitis was assessed in all cases.…”

“…In previous work (16) we have found increased mRNA levels of manganese-dependent SOD (Mn-SOD) in peripheral blood mononuclear cells (PBMC) from patients with chronic HCV infection, suggesting that oxidative stress might be present in peripheral lymphocytes in this condition. Since the therapeutic response to IFN depends critically on the ability of this compound to stimulate an efficient antiviral immune response (17,18), and oxidative stress is known to impair the effector functions of lymphocytes (3), we decided to investigate further the presence of oxidative stress in PBMC from HCV-infected individuals.…”

Hepatitis C virus envelope components alter localization of hepatocyte tight junction-associated proteins and promote occludin retention in the endoplasmic reticulum

“…6,20 Oxidative stress is considered to contribute to the pathogenesis of HCV-infected patients. 21 Additionally, the expression of either the entire polyprotein or the nonstructural proteins of HCV has been associated with the generation of reactive oxygen species. 22,23 Our experiments showed that localization of TJ-associated proteins was altered in cells harboring genomic but not subgenomic replicons.…”