Gentiana lutea attenuates hepatotoxicity induced by ketoconazole in rats by fortifying the cellular antioxidant defense system

Abstract

Ketoconazole (KET) is a broad-spectrum antifungal drug that has been reported to induce hepatotoxicity in humans and animals. The safe guarding response of Gentiana extract (GEN) against KET-induced hepatotoxicity was investigated in this study using male Wistar rats. GEN ethanol extract was orally administered to rats (1 g/kg b.wt) for 30 days. Beginning on day 26, KET was intraperitoneally administered once daily for 5 days using a dose of 100 mg/kg. The hepatoprotective effects of GEN against liver damage induced by KET were monitored through significant decrements in serum levels of aminotransferase and alpha-fetoprotein as well as recorded hepatic histopathological changes. The hepatotoxicity of KET treatment was accompanied with a marked oxidative damage to hepatic proteins, lipids, and DNA, and depletions in natural antioxidants (glutathione and superoxide dismutase). GEN inhibited KET-induced oxidative stress by diminishing lipid peroxidation, protein carbonylation, and oxidative stress in DNA. These free radical mediated effects were greatly decreased with GEN treatment. This study suggests that GEN’s hepatoprotective effects could be attributed to its antioxidant properties.