Effect of ursodeoxycholic acid on hepatic steatosis in rats

Ursodeoxycholic acid (UDCA) has been shown to have hepatoprotective effects in various liver diseases. This drug has also been found to be effective in patients with nonalcoholic steatohepatitis, improving hepatic steatosis (HS) significantly. The aim of this study was to evaluate whether UDCA has an effect on both preventing and regressing HS in rats. To induce fatty liver, a choline-deficient diet (CDD) was used. For the rats assigned to receive UDCA, a 1.5% UDCA solution was administered at a dose of 25 mg/kg/day using an oral feeding tube. Assesment of HS was based on the quantification of percentage of hepatocytes containing lipid vacuoles. Forty-three male Wistar rats were randomly divided into two protocols. In protocol I, 7 rats were fed a standard diet (SD) plus UDCA for 30 days (control group). In protocol II, 19 rats were fed CDD and 17 rats were fed CDD plus UDCA for 30 days. At the end of this period, after performing liver biopsies, either SD or SD plus UDCA was started in both CDD-fed rats and CDD plus UDCA-fed rats for 30 days in a random order without the knowledge of the degrees of steatosis developed. At the end of this period, liver biopsies were repeated in order to evaluate whether UDCA has an effect on the regression of HS. In protocol I, there were no specific findings on the histological examination of the livers at 30 days. In protocol II, the percentage of HS in CDD plus UDCA-fed rats was significantly lower than CDD-fed rats at the end of the same period (percentage of steatosis, mean ± sd: 12.2 ± 29.6 to 23.2 ± 34.1 respectively, P = 0.0201); after starting either SD or SD plus UDCA, steatosis was almost completely regressed at 30 days in all rats that developed that steatogenic changes. UDCA seems to prevent HS in rats; addition of UDCA to SD does not cause a further contribution in regressing HS.