Preclinical Benefit of Silymarin on Ketoconazole-induced Hepatotoxicity

Abstract

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 (180-200g) 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 total bilirubin, amino transferases, lactate dehydrogenase, gamma-glutamyl transferase, alkaline phosphatase and liver malondialdehyde levels when compared to control. KT significantly (p<0.01) decreased body weight, and significantly (p<0.01) decreased liver catalase, glutathione peroxidase, superoxide dismutase, and glutathione levels when compared to control. KT caused hepatocelluar 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. Various doses of SL restored liver histology. Conclusion: SL may have clinical benefit in KT-induced hepatotoxicity.

Keywords

• Ketoconazole
• hepatoprotection
• silymarine
• liver

Supporting Institution

Department of Pharmacology /Toxicology, Faculty of Pharmacy, Madonna University, Rivers State, Nigeria

Project Number

no 55

Ethical Statement

The animals were handle according to the Guide for the Care and Use of Laboratory Animals. 8th edition,

Thanks

Thanks for the privilege of submitting this manuscript

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