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Effect of epomediol on ethinyloestradiol-induced changes in bile acid and cholesterol metabolism in rats

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SUMMARY

1. Epomediol is a terpenoid compound that has been reported to stimulate bile acid synthesis and to reverse 17α- 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 7α-hydroxylase and hydroxy-3- methylglutaryl coenzyme A reductase activities were significantly increased in epomediol-treated rats (+30 and +96%, respectively). Cholesterol 7α-hydroxylase activity was significantly reduced by ethinyloestradiol (–22%) and did not differ from control values in animals receiving epomediol plus ethinyloestradiol. Levels of cholesterol 7α-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 7α-hydroxylase. Changes in bile acid metabolism contribute to the effects of epomediol in rats with ethinyloestradiol-induced cholestasis.
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Keywords: bile acid; cholesterol 7α-hydroxylase; epomediol; ethinyloestradiol; hydroxy-3-methylglutaryl coenzyme A reductase

Document Type: Research Article

Publication date: August 1, 2001

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