Ezetimibe prevents the formation of oestrogen-induced cholesterol gallstones in mice.
Eur J Clin Invest
; 44(12): 1159-68, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25303682
ABSTRACT
BACKGROUND:
Oestrogen is an important risk factor for cholesterol cholelithiasis not only in women of childbearing age taking oral contraceptives and postmenopausal women undergoing hormone replacement therapy, but also in male patients receiving oestrogen therapy for prostatic cancer. In women, hormonal changes occurring during pregnancy markedly increase the risk of developing gallstones. We investigated whether the potent cholesterol absorption inhibitor ezetimibe could prevent the formation of oestrogen-induced cholesterol gallstones in mice.DESIGN:
Following ovariectomy, female AKR mice were implanted subcutaneously with pellets releasing 17ß-estradiol at 6 µg/day and fed a lithogenic diet supplemented with ezetimibe in doses of 0 or 8 mg/kg/day for 8 weeks. Cholesterol crystallization and gallstone prevalence, lipid concentrations and composition in bile, and biliary lipid output were analysed by physical-chemical methods. Intestinal cholesterol absorption efficiency was determined by faecal dual-isotope ratio methods.RESULTS:
Ezetimibe inhibited intestinal cholesterol absorption, while significantly reducing hepatic secretion of biliary cholesterol. Consequently, bile was desaturated through the formation of numerous unsaturated micelles and gallstones were prevented by ezetimibe in mice exposed to high doses of oestrogen and fed the lithogenic diet. Ezetimibe did not influence mRNA levels of the classical oestrogen receptors α (ERα) and ERß, as well as a novel oestrogen receptor the G protein-coupled receptor 30 (GPR30) in the liver.CONCLUSIONS:
Ezetimibe protects against the oestrogen-mediated lithogenic actions on gallstone formation in mice. Our finding may provide an efficacious novel strategy for the prevention of cholesterol gallstones in high-risk subjects, especially those exposed to high levels of oestrogen.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Azetidinas
/
Cálculos Biliares
/
Anticolesterolemiantes
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Clin Invest
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos