Therapeutic benefit of ursodeoxycholic acid in tamoxifen-induced hepatotoxicity in Wistar rats

Abstract

Background. The clinical use of tamoxifen (TAM) may cause hepatotoxicity. Ursodeoxycholic acid (UDCA) has promising liver protective activity. This study assessed the protective effect of UDCA on TAM-induced hepatotoxicity in rats.Material and methods. Thirty five adult female Wistar rats were grouped into 7 of n=5/group. The rats were treated for 10 days as follows: Group 1: Water (10 mL/kg/day; placebo control) per oral [p.o], group 2: Ethanol 1% (1mL/kg/day; vehicle control) intraperitoneally (i.p), group 3: UDCA (40 mg/kg/day/p.o) and group 4: TAM (45 mg/kg/day) i.p. Groups 5-7 were pretreated with UDCA (10, 20 and 40 mg/kg), before daily treatment with TAM (45 mg/kg/day) i.p, respectively. On day 11, blood samples were collected and assessed for serum liver biomarkers. Liver samples were evaluated for oxidative stress markers and histology.Results. Significantly (p<0.05) decreased body weight and significantly (p<0.01) increased liver weight occurred in TAM- treated rats when compared to placebo control. TAM significantly (p<0.001) increased serum alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, aminotransferases, bilirubin, high density lipoprotein cholesterol levels and liver malondialdehyde levels when compared to control. TAM significantly (p<0.001) decreased liver glutathione, catalase, glutathione peroxidase, superoxide dismutase, serum total protein, albumin total cholesterol, low density lipoprotein cholesterol and triglyceride levels when compared to control. Steatosis and necrotic changes occurred in TAM-treated rats. UDCA pretreatment significantly prevents TAM-induced changes in serum biochemical markers, and oxidative stress indices in a dose-related fashion when compared to TAM. UDCA prevents TAM-induced changes in liver histology.Conclusion. UDCA may be clinically effective for TAM associated hepatotoxicity.