Resveratrol abrogates 5-flourouracil -induced hepatotoxicity: A preclinical study

Abstract

The manifestation of acute hepatotoxicity caused by 5-fluorouracil could be characterized by asymptomatic elevations of liver enzymes, hepatic steatosis and fuminant hepatitis. Natural antioxidants have potential as excellent treatment strategy against diseases and drug-induced toxicities. This study assessed the potential of resveratrol (RSV) to abrogate the hepatotoxic effect of 5-FU in rats. Forty adult male albino rats (240g± 20g) were randomized and orally supplemented with RSV (10, 20 and 40 mg/kg/day) prior to the administration of 5-FU (20mg/kg/day) intraperitoneally for 5 days. On day 6, after weighing, the rats were anesthetized, blood samples were collected and centrifuged and sera obtianed. Liver tissues were harvested and weighed. Sera and liver samples were evaluated for biochemical parameters. Liver tissues were assessed for histology. Body weight was significantly (p <0.05) decreased where as liver weight was significantly (p <0.01) increased in 5-FU administered rats in relation to control. Serum and liver lactate dehydrogenase, aminotransferases (AST), alkaline phosphatase, gamma-glutamyl transferase, total bilirubin, conjugated bilirubin and malondialdehyde levels were significantly (p <0.001) increased in 5FU-administered rats in relation to control. Liver glutathione peroxidase, catalase, glutathione and superoxide dismutase levels were significantly (p <0.001) decreased in 5-FU administered rats in relation to control. The liver of 5-FU administered rats showed necrosis and steatosis. The hepatotoxic effect of 5-FU was abrogated in a dose-related fashion in RSV 10 mg/kg (p <0.05), 20mg/kg (p <0.01), and RSV 40mg/kg (p <0.001) supplemented rats in relation to 5-FU. RVS may be clinically effective against 5-FU-induced hepatotoxicity.

Keywords

• 5-fluoroural
• liver
• toxicity
• resveratrol
• mitigation
• rat