Therapeutic Benefit of Ursodeoxycholic Acid in Tamoxifen-Induced Hepatotoxicity in Rats

Abstract

The use of tamoxifen (TAM) for breast cancer treatment may cause hepatotoxicity. Ursodeoxycholic acid (UDCA) is a potential liver protective chemical compound. The protective effect of UDCA on TAM-induced hepatotoxicity in rats was analyzed in this study. Thirty five adult female Wistar rats grouped into 7 of n=5/group were used. The rats were treated for 10 days as follows: Group 1: (Placebo control) Water (10 mL/kg/day/oral), group 2: (Vehicle control) Ethanol 1% (1mL/kg/day) intraperitoneally (i.p), group 3: UDCA (40 mg/kg/day/oral) and group 4: TAM (45 mg/kg/day) i.p. Groups 5-7 were pretreated with UDCA (10, 20 and 40 mg/kg/day/oral) before treatment with TAM (45 mg/kg/day) i.p, respectively. On day 11, blood samples were collected and evaluated for biochemical markers. Liver tissues were analyzed for oxidative stress markers and histology. Results: TAM decreased body weight and increased liver weight significantly (p<0.01) when compared to the placebo control. Serum bilirubin, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, aminotransferases, high density lipoprotein cholesterol and liver malondialdehyde levels were significantly (p<0.001) elevated by TAM when compared to control. TAM significantly (p<0.001) decreased serum triglyceride, very low density lipoprotein cholesterol, total cholesterol, liver glutathione, catalase, superoxide dismutase and glutathione peroxidase levels when compared to the control. TAM caused liver steatosis and necrosis in rats. However, UDCA pretreatment significantly prevented the aforementioned changes caused by TAM in a dose-related fashion. UDCA may be a therapeutic option for TAM associated hepatotoxicity.