Oxidative stress, endogenous antioxidants, alcohol, and hepatitis C: pathogenic interactions and therapeutic considerations.
Hepatitis C virus (HCV) is a blood-borne pathogen that was identified as an etiologic agent of non-A, non-B hepatitis in 1989. HCV is estimated to have infected at least 170 million people worldwide. The majority of patients infected with HCV do not clear the virus and become chronically infected, and chronic HCV infection increases the risk for hepatic steatosis, cirrhosis, and hepatocellular carcinoma. HCV induces oxidative/nitrosative stress from multiple sources, including inducible nitric oxide synthase, the mitochondrial electron transport chain, hepatocyte NAD(P)H oxidases, and inflammation, while decreasing glutathione. The cumulative oxidative burden is likely to promote both hepatic and extrahepatic conditions precipitated by HCV through a combination of local and more distal effects of reactive species, and clinical, animal, and in vitro studies strongly point to a role of oxidative/nitrosative stress in HCV-induced pathogenesis. Oxidative stress and hepatopathogenesis induced by HCV are exacerbated by even low doses of alcohol. Alcohol and reactive species may have other effects on hepatitis C patients such as modulation of the host immune system, viral replication, and positive selection of HCV sequence variants that contribute to antiviral resistance. This review summarizes the current understanding of redox interactions of HCV, outlining key experimental findings, directions for future research, and potential applications to therapy.
Department of Molecular Cell Biology, School of Natural Sciences, University of California at Merced, Merced, CA 95343, USA. jchoi@ucmerced.edu
Jinah
J
Choi
D000438:Alcohols / Q000009:adverse effects*; D000975:Antioxidants; D000998:Antiviral Agents / Q000627:therapeutic use*; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D006801:Humans; D018384:Oxidative Stress
D000438:Alcohols; D000975:Antioxidants; D000998:Antiviral Agents