| Abstrakt: |
Background: Ketoconazole (KT) use has raised safety concern regarding hepatotoxicity. Silymarin (SL) is a natural bioactive substance with activities on a wide range of human pathologies. The protective activity of SL against KT-induced hepatotoxicity in rats was determined in this study. Methods: Thirty adult Wistar rats of both sexes (220-300g) of n= 5/group were used. Groups I (Control) and II were orally administered with normal saline (0.2mL/day) and SL (200 mg/kg/day), respectively, whereas group III was orally administered with KT (200 mg/kg/day) for 28 days. Groups IV-VI were orally supplemented with SL (50 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day) before the administration of KT (200 mg/kg/day) for 28 days, respectively. On day 29, the rats were anesthetized and blood samples were collected and examined for biochemical markers. Liver tissues were collected and assessed for oxidative stress markers and histology. Results: KT significantly (p<0.01) increased liver weight, and significantly (p<0.001) increased serum bilirubin, amino transferases, lactate dehydrogenase, gamma-glutamyl transferase, alkaline phosphatase, and liver malondialdehyde levels when compared to the control. KT significantly (p<0.01) decreased body weight, and significantly (p<0.001) decreased liver catalase, glutathione peroxidase, superoxide dismutase, and glutathione levels when compared to the control. KT caused hepatocellular necrosis. However, body, and liver weights and the aforementioned biochemical and oxidative stress markers were significantly restored in a dose-related fashion by SL supplementation at 50 mg/kg (p<0.05), 100 mg/kg (p<0.01), and 200 mg/kg (p<0.001) when compared to KT. The various doses of SL restored liver histology. Conclusion: SL may have clinical benefit in KT-induced hepatotoxicity. [ABSTRACT FROM AUTHOR] |
