{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:06:36Z","timestamp":1791648396406,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T00:00:00Z","timestamp":1415059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK73917"],"award-info":[{"award-number":["DK73917"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u2010induced cholesterol gallstones in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>\n                      Following ovariectomy, female\n                      <jats:styled-content style=\"fixed-case\">AKR<\/jats:styled-content>\n                      mice were implanted subcutaneously with pellets releasing 17\u03b2\u2010estradiol at 6\u00a0\u03bcg\/day and fed a lithogenic diet supplemented with ezetimibe in doses of 0 or 8\u00a0mg\/kg\/day for 8\u00a0weeks. Cholesterol crystallization and gallstone prevalence, lipid concentrations and composition in bile, and biliary lipid output were analysed by physical\u2013chemical methods. Intestinal cholesterol absorption efficiency was determined by faecal dual\u2010isotope ratio methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                      levels of the classical oestrogen receptors \u03b1 (ER\u03b1) and ER\u03b2, as well as a novel oestrogen receptor the G protein\u2010coupled receptor 30 (GPR30) in the liver.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ezetimibe protects against the oestrogen\u2010mediated lithogenic actions on gallstone formation in mice. Our finding may provide an efficacious novel strategy for the prevention of cholesterol gallstones in high\u2010risk subjects, especially those exposed to high levels of oestrogen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.12350","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T10:18:39Z","timestamp":1412849919000},"page":"1159-1168","source":"Crossref","is-referenced-by-count":16,"title":["Ezetimibe prevents the formation of oestrogen\u2010induced cholesterol gallstones in mice"],"prefix":"10.1111","volume":"44","author":[{"given":"Ornella","family":"de Bari","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Division of Gastroenterology and Hepatology Saint Louis University School of Medicine St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Gastroenterology and Hepatology Saint Louis University School of Medicine St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Portincasa","sequence":"additional","affiliation":[{"name":"Clinica Medica \u201cA. 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