Low protein diet protects against ethinyl estradiol-induced cholestasis

Abstract

Ethinyl estradiol (EE) administration is associated with impairment of bile formation (cholestasis) in both humans and animals. Since low protein diets (LPD) interfere with normal bile secretory function, we examined bile flow, the bile acid (BA) secretory rate and biliary cholesterol (CH) and phospholipid (PH) output in rats fed LPD and given EE (5 mg/kg for body weight 4 days). In another experimental series, we assessed the effects of LPD and EE on the secretory rate maximum (SRm) of cholic acid. Rats fed LPD had significantly lower bile flow and biliary BA secretion rate than animals given an adequate or normal protein diet (NPD). In the NPD group, EE resulted in a cholestatic response. In contrast, bile flow in LPD rats, was not significantly changed, and the BA secretory rate was increased in comparison with corresponding LPD controls not receiving EE. Biliary PH output was enhanced in both the controls and LPD-fed, EE-treated animals. CH secretion was decreased in the NPD and LPD groups as a result of EE administration, indicating a dissociation between bile acid and PH or CH secretion in bile. In rats fed an adequate diet, EE reduced the SRm of cholic acid but in the LPD group, the SRm was not inhibited and even reached higher values than in the untreated controls. The changes in bile flow paralleled those of the BA secretory rate. Estimation of the bile acid dependent (BADF) and independent fractions (BAIF) of bile flow indicated that EE depressed BAIF in the NPD and LPD groups. However, BADF and the choleretic activity of BA secreted were markedly enhanced in the LPD group, which explains, in part, the observation that EE did not induce a cholestatic response in rats fed LPD.