Interferon-alpha enhances biological defense activities against oxidative stress in cultured rat hepatocytes and hepatic stellate cells.
Oxidative stress has been implicated as a cause of hepatic fibrosis, and hepatic stellate cells (HSCs), which are the most important collagen-producing cell types, have been reported to be activated by lipid peroxidation products. Antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) provide a defense system that plays a critical role in protecting the cell from free radical damage, particularly lipid peroxidation. To elucidate the antioxidant activity of interferon-alpha (IFN-alpha), the effects of IFN-alpha on rat hepatocytes undergoing oxidative stress and HSCs in primary culture as well as isolated rat liver mitochondria were examined. IFN-alpha was observed to dose-dependently increase the immunoreactive protein levels of copper, zinc-and manganese-dependent SOD as well as the enzyme activities of GPx, and decrease the lipid peroxidation product levels and oxidative burst both in stressed hepatocytes and activated HSCs; GPx activities, however, were not detected in the latter cells. IFN-alpha also inhibited HSC activation and lipid peroxidation in liver mitochondria. These findings suggest that IFN-alpha may enhance biological defense activities against oxidative stress and function as a potent fibrosuppressant by protecting hepatocytes and hepatic stellate cells from lipid peroxidation in vivo.
D000199:Actins / Q000032:analysis; D000818:Animals; D015415:Biomarkers; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000032:analysis; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology; D008103:Liver Cirrhosis / Q000209:etiology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000032:analysis
D000199:Actins; D015415:Biomarkers; D005290:Ferric Compounds; D016898:Interferon-alpha; D016877:Oxidants; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate