Effect of epomediol on ethinyloestradiol-induced changes in bile acid and cholesterol metabolism in rats.
1. Epomediol is a terpenoid compound that has been reported to stimulate bile acid synthesis and to reverse 17alpha- 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 7alpha-hydroxylase and hydroxy-3- methylglutaryl coenzyme A reductase activities were significantly increased in epomediol-treated rats (+30 and +96%, respectively). Cholesterol 7alpha-hydroxylase activity was significantly reduced by ethinyloestradiol (-22%) and did not differ from control values in animals receiving epomediol plus ethinyloestradiol. Levels of cholesterol 7alpha-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 7alpha-hydroxylase. Changes in bile acid metabolism contribute to the effects of epomediol in rats with ethinyloestradiol-induced cholestasis.
Cuevas
M J
MJ
Department of Physiology, University of León, University Campus, 24071 León, Spain.
Mauriz
J L
JL
Almar
M
M
Collado
P S
PS
González-Gallego
J
J
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002756:Cholagogues and Choleretics / Q000494:pharmacology* / Q000627:therapeutic use; D002779:Cholestasis / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D002784:Cholesterol / Q000378:metabolism*; D004347:Drug Interactions; D045166:Estradiol Congeners / Q000009:adverse effects / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology* / Q000627:therapeutic use
D001647:Bile Acids and Salts; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002756:Cholagogues and Choleretics; D045166:Estradiol Congeners; D020011:Protective Agents; D012333:RNA, Messenger; D013729:Terpenes; D004997:Ethinyl Estradiol; D002784:Cholesterol; C031365:epomediol