Ezetimibe prevents cholesterol gallstone formation in mice

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dc.catalogadorgrr
dc.contributor.authorZuñiga, Silvia Eugenia
dc.contributor.authorMolina, Héctor
dc.contributor.authorAzócar, Lorena
dc.contributor.authorAmigo Boker, Ludwig Peter
dc.contributor.authorNervi Oddone, Flavio
dc.contributor.authorPimentel Muller, Fernando Ernesto
dc.contributor.authorJarufe Cassis, Nicolas Patricio
dc.contributor.authorArrese Jimenez, Marco Antonio
dc.contributor.authorLammert, Frank
dc.contributor.authorMiquel Poblete, Juan Francisco
dc.date.accessioned2024-08-07T23:24:10Z
dc.date.available2024-08-07T23:24:10Z
dc.date.issued2008
dc.description.abstractBackground: Intestinal cholesterol absorption may influence gallstone formation and its modulation could be a useful therapeutic strategy for gallstone disease (GSD). Ezetimibe (EZET) is a cholesterol-lowering agent that specifically inhibits intestinal cholesterol absorption. Aims: To test whether EZET can prevent gallstone formation in mice. Methods/Results: Gallstone-susceptible C57BL/6 inbred mice were fed control and lithogenic diets with or without simultaneous EZET administration. Lithogenic diet increased biliary cholesterol content and secretion, and induced sludge or gallstone formation in 100% of the animals. EZET administration reduced intestinal cholesterol absorption by 90% in control animals and by 35% in mice receiving the lithogenic diet. EZET prevented the appearance of cholesterol crystals and gallstones. In addition, mice fed the lithogenic diet plus EZET exhibited a 60% reduction in biliary cholesterol saturation index. Of note, EZET treatment caused a significant increase in bile flow (+50%, P < 0.01) as well as bile salt, phospholipid and glutathione secretion rates (+60%, +44% and +100%, respectively, P < 0.01), which was associated with a moderately increased expression of hepatic bile salt transporters. In addition, relative expression levels of Nieman-Pick C1 like 1 (NPC1L1) in the enterohepatic axis in humans were assessed. Expression levels of NPC1L1 were 15-to 30-fold higher in the duodenum compared with the liver at transcript and protein levels, respectively, suggesting preferential action of EZET on intestinal cholesterol absorption in humans. Conclusions: In a murine model of GSD, EZET prevented gallstone formation by reducing intestinal cholesterol absorption and increasing bile salt-dependent and -independent bile flow. EZET could be useful in preventing GSD disease in susceptible patients.
dc.description.funderFONDECYT
dc.fuente.origenORCID
dc.identifier.doi10.1111/j.1478-3231.2008.01808.x
dc.identifier.eissn1478-3231
dc.identifier.eissn1478-3231
dc.identifier.issn1478-3223
dc.identifier.pubmedid18783541
dc.identifier.scopusidSCOPUS_ID:2-s2.0-84912073431
dc.identifier.urihttps://doi.org/10.1111/j.1478-3231.2008.01808.x
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/87349
dc.identifier.wosidWOS:000257706600006
dc.information.autorucMedicina;Azócar L;S/I;1006324
dc.information.autorucMedicina;Molina H;S/I;1001203
dc.information.autorucEscuela de Medicina; Zuñiga, Silvia Eugenia; S/I; 135611
dc.information.autorucEscuela de Medicina; Amigo Boker, Ludwig Peter; S/I; 62028
dc.information.autorucEscuela de Medicina; Nervi Oddone, Flavio; 0000-0002-6642-7985; 99156
dc.information.autorucEscuela de Medicina; Pimentel Muller, Fernando Ernesto; S/I; 58222
dc.information.autorucEscuela de Medicina; Jarufe Cassis, Nicolas Patricio; 0000-0002-9166-3015; 104492
dc.information.autorucEscuela de Medicina; Arrese Jimenez, Marco Antonio; 0000-0002-0499-4191; 76095
dc.information.autorucEscuela de Medicina; Miquel Poblete, Juan Francisco; 0000-0002-0526-4377; 72216
dc.issue.numero7
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final947
dc.pagina.inicio935
dc.revistaLiver International
dc.rightsacceso restringido
dc.subjectBiliary lipids
dc.subjectCholesterol gallstones
dc.subjectEzetimibe
dc.subjectGall bladde
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleEzetimibe prevents cholesterol gallstone formation in mice
dc.typeartículo
dc.volumen28
sipa.codpersvinculados1006324
sipa.codpersvinculados1001203
sipa.codpersvinculados135611
sipa.codpersvinculados62028
sipa.codpersvinculados99156
sipa.codpersvinculados58222
sipa.codpersvinculados104492
sipa.codpersvinculados76095
sipa.codpersvinculados72216
sipa.trazabilidadHistorial Académico;09-07-2021
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