LOW-PROTEIN DIET PROTECTS AGAINST ETHINYL ESTRADIOL-INDUCED CHOLESTASIS

Ethinyl estradiol (EE) administration is associated with impairment of bile formation (cholestasis) in both humans and animals. Since low pr otein diets (LPD(a)) interfere with normal bile secretory function, we examined bile flow, the bile acid (BA) secretory rate and biliary cho lesterol (CH) and phospholipid (PH) output in rats fed LPD and given E E (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 b iliary BA secretion rate than animals given an adequate or normal prot ein diet (NPD). In the NPD group, EE resulted in a cholestatic respons e. In contrast, bile flow in LPD rats, was not significantly changed, and the BA secretory rate was increased in comparison with correspondi ng LPD controls not receiving EE. Biliary PH output was enhanced in bo th the controls and LPD-fed, EE-treated animals. CH secretion was decr eased in the NPD and LPD groups as a result of EE administration, indi cating a dissociation between bile acid and PR 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 va lues than in the untreated controls. The changes in bile flow parallel ed those of the BA secretory rate. Estimation of the bile acid depende nt (BADF) and independent fractions (BAIF) of bile flow indicated that EE depressed BAIF in the NPD and LPD groups. However, BADF and the ch oleretic activity of BA secreted were markedly enhanced in the LPD gro up, which explains, in part, the observation that EE did not induce a cholestatic response in rats fed LPD.