Effects of ethyl 4-chloro-2-methylphenoxyacetate on bile composition in golden hamsters.

Abstract

The effects of ethyl 4-chloro-2-methylphenoxyacetate (MCPA) on the cholesterol levels in the liver, serum and gallbladder bile, the composition of both biliary lipids and bile acids, and the hepatic enzyme activities relating to the bile acid formation were investigated in male golden hamsters. MCPA was administered orally to the animals at the doses of 200, 500 and 1,000 mg/kg/day for 2 weeks. Clofibrate (500 mg/kg/day) was also tested for comparison, because of its similarity to MCPA in chemical structure and pharmacological actions. Body weight gain was slightly decreased, but liver to body weight ratio was increased in the MCPA groups of 500 and 1,000 mg/kg and also in the clofibrate group. In these groups, the cholesterol level in the liver was decreased but that in bile was increased. The composition of biliary bile acids was also changed in both the MCPA groups (500 and 1,000 mg/kg) and the clofibrate group, but in a different manner; the levels and proportions of secondary bile acids were increased in the MCPA groups, while those of cholic acid and deoxycholic acid were decreased in the clofibrate group. These results indicate that MCPA and clofibrate may affect cholesterol catabolism differently, although these two compounds contain the same chlorinated phenoxy acid moiety. The increased level of cholesterol in bile might lead to the formation of cholesterol gallstone, which is frequently found in patients with gallbladder cancer. It is inferred that exposure to MCPA could be a risk factor for gallbladder cancer, which was initiated with some chemical carcinogens, because it increased the levels and proportions of both cholesterol and secondary bile acids in bile.