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Effect of epomediol on ethinyloestradiol‐induced changes in bile acid and cholesterol metabolism in rats
Author(s) -
Cuevas María J,
Mauriz José L,
Almar Mar,
Collado Pilar S,
GonzálezGallego Javier
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03496.x
Subject(s) - endocrinology , medicine , bile acid , cholesterol , metabolism , secretion , reductase , ursodeoxycholic acid , chemistry , biology , enzyme , biochemistry
SUMMARY 1. Epomediol is a terpenoid compound that has been reported to stimulate bile acid synthesis and to reverse 17 α ‐ ethinyloestradiol‐induced cholestasis. The aim of the present study was to investigate the contribution of changes in bile acid and cholesterol metabolism to the protective effects of epomediol in ethinyloestradiol‐treated rats. Animals received epomediol for 5 days at 100 mg/kg daily, i.p., ethinyloestradiol for 5 days at 5 mg/kg, s.c., or a combination of both drugs. 2. When compared with control animals, epomediol treatment resulted in a significant increase in bile flow (+42%) and in the secretion of bile acids (+74%) and cholesterol (+42%). Ethinyloestradiol administration caused a significant decrease in bile flow (–43%), bile acid secretion (–37%) and cholesterol secretion (–45%). Bile flow, bile acid secretion and cholesterol secretion were significantly increased in animals receiving ethinyloestradiol plus epomediol compared with ethinyloestradiol‐treated rats (+13, +29 and +31%, respectively). 3. Both cholesterol 7 α ‐hydroxylase and hydroxy‐3‐ methylglutaryl coenzyme A reductase activities were significantly increased in epomediol‐treated rats (+30 and +96%, respectively). Cholesterol 7 α ‐hydroxylase activity was significantly reduced by ethinyloestradiol (–22%) and did not differ from control values in animals receiving epomediol plus ethinyloestradiol. Levels of cholesterol 7 α ‐hydroxylase mRNA were elevated (+41%) by epomediol, but were not significantly modified by ethinyloestradiol or ethinyloestradiol plus epomediol. 4. It is concluded that epomediol enhances bile acid secretion by increasing the expression of cholesterol 7 α ‐hydroxylase. Changes in bile acid metabolism contribute to the effects of epomediol in rats with ethinyloestradiol‐induced cholestasis.