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Gallbladder stones are thought to damage the gallbladder epithelium and trigger chronic inflammation. Preneoplastic lesions that arise in such an inflammatory microenvironment can eventually develop into invasive carcinoma, through mechanisms that are not fully understood. Here, we developed a novel gallbladder preneoplasia mouse model through the administration of two lithogenic diets (a low\u2010 or a high\u2010cholesterol diet) in wild\u2010type C57BL\/6 mice over a period of 9\u00a0months. Additionally, we evaluated the chemopreventive potentials of the anti\u2010inflammatory drug aspirin and the cholesterol absorption inhibitor ezetimibe. Both lithogenic diets induced early formation of gallbladder stones, together with extensive inflammatory changes and widespread induction of metaplasia, an epithelial adaptation to tissue injury. Dysplastic lesions were presented only in mice fed with high\u2010cholesterol diet (62.5%) in late stages (9th month), and no invasive carcinoma was observed at any stage. The cholesterol absorption inhibitor ezetimibe inhibited gallbladder stone formation and completely prevented the onset of metaplasia and dysplasia in both lithogenic diets, whereas aspirin partially reduced metaplasia development only in the low\u2010cholesterol diet setting. This model recapitulates several of the structural and inflammatory findings observed in human cholecystolithiasic gallbladders, making it relevant for the study of gallbladder carcinogenesis. In addition, our results suggest that the use of cholesterol absorption inhibitors and anti\u2010inflammatory drugs can be evaluated as chemopreventive strategies to reduce the burden of GBC among high\u2010risk populations.<\/jats:p>","DOI":"10.1002\/1878-0261.12766","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T22:06:55Z","timestamp":1595023615000},"page":"2834-2852","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Evaluation of the chemopreventive potentials of ezetimibe and aspirin in a novel mouse model of gallbladder preneoplasia"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3785-2146","authenticated-orcid":false,"given":"Lorena","family":"Rosa","sequence":"first","affiliation":[{"name":"Doctorado en Ciencias menci\u00f3n Biolog\u00eda Celular y Molecular Aplicada Universidad de La Frontera Temuco Chile"},{"name":"Departamento de 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