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Graphical Abstract:

Background: Ketoconazole (KET) is a broad-spectrum antifungal drug that has been reported to induce hepatotoxicity in humans and animals. Methods: 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. Results: 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. Conclusions: This study suggests that GEN’s hepatoprotective effects could be attributed to its antioxidant properties.