ENHANCED BILIARY-EXCRETION OF CANALICULAR MEMBRANE ENZYMES IN ETHYNYLESTRADIOL-INDUCED CHOLESTASIS - EFFECTS OF URSODEOXYCHOLIC ACID ADMINISTRATION

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dc.contributor.authorARRESE, M
dc.contributor.authorPIZARRO, M
dc.contributor.authorSOLIS, N
dc.contributor.authorKOENIG, C
dc.contributor.authorACCATINO, L
dc.date.accessioned2024-01-10T13:48:05Z
dc.date.available2024-01-10T13:48:05Z
dc.date.issued1995
dc.description.abstractCholestasis is associated with a marked increase in the release of canalicular membrane enzymes into bile. This phenomenon has been related to an increased lability of these canalicular membrane integral proteins to the solubilizing effects of secreted bile salts. To further characterize the effects of oral ursodeoxycholic acid (UDCA) administration on ethynylestradiol (EE)-induced cholestasis, the influence of this bile acid on changes in biliary excretion of membrane-bound enzymes was investigated Bile flow, basal bile salt and biliary lipid secretory rates, the maximum secretory rate of taurocholate TC SRm), and the biliary excretion of the canalicular membrane-bound ectoenzymes alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) were measured in rats after EE and/or UDCA administration. The activities of ALP, GGT and Na+,K+-ATPase in purified isolated canalicular and sinusoidal membrane fractions and the ultrastructure of hepatic acinus, including histochemical studies of ALP distribution, were also examined. EE significantly reduced bile flow, bile salt and biliary lipid secretory rates, and TC SRm, and caused dilatation and loss of microvilli at the canalicular pole of hepatocytes. Biliary excretion of ALP increased 2-fold, whereas biliary excretion of GGT was unchanged. The relationship between biliary excretion of ALP or GGT and bile salt secretion (units of enzyme activity secreted per nanomole of bile salt) was greater in EE-treated rats compared with controls (2.1- and 1.5-fold greater for ALP and GGT, respectively), indicating that in EE-induced cholestasis more enzyme was released into bile per nanomole of bile salt. Na+,K+-ATPase activity in sinusoidal membrane fraction was reduced significantly, whereas ALP activity increased in both membrane fractions in EE-treated rats. The histochemical distribution of ALP in the acinus showed a strong reaction in acinar zone 3 and at both the canalicular and sinusoidal membranes. Oral administration of UDCA prevented EE-induced bile secretory failure by normalizing bile flow, bile salt and biliary phospholipid secretory rates, and TC SRm. UDCA also prevented the EE-induced changes in the biliary excretion of enzymes. On the contrary, UDCA did not modify either the enzyme activity in isolated membrane fractions or the morphological or ALP histochemical changes associated with EE administration. These data indicate that in BE-induced cholestasis changes occur at the canalicular membrane, enabling this portion of the plasma membrane to be more susceptible to the solubilizing effect of bile salt, and that oral administration of UDCA prevents bile secretory failure and changes in the biliary excretion of ALP and GGT in EE-treated rats.
dc.fechaingreso.objetodigital2024-03-18
dc.format.extent10 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/0006-2952(95)00262-X
dc.identifier.issn0006-2952
dc.identifier.pubmedidMEDLINE:7488238
dc.identifier.urihttps://doi.org/10.1016/0006-2952(95)00262-X
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79332
dc.identifier.wosidWOS:A1995TC82300015
dc.information.autorucMedicina;Accatino L;S/I;99016
dc.issue.numero8
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final1232
dc.pagina.inicio1223
dc.publisherPERGAMON-ELSEVIER SCIENCE LTD
dc.revistaBIOCHEMICAL PHARMACOLOGY
dc.rightsacceso restringido
dc.subjectCHOLESTASIS
dc.subjectBILE ACIDS
dc.subjectALKALINE PHOSPHATASE
dc.subjectPLASMA MEMBRANE ENZYMES
dc.subjectURSODEOXYCHOLIC ACID
dc.subjectGAMMA-GLUTAMYL TRANSPEPTIDASE
dc.subjectBILE-DUCT LIGATION
dc.subjectALKALINE-PHOSPHATASE ACTIVITY
dc.subjectESTROGEN-INDUCED CHOLESTASIS
dc.subjectPLASMA-MEMBRANE
dc.subjectRAT-LIVER
dc.subjectADAPTIVE REGULATION
dc.subjectSALT TRANSPORT
dc.subjectETHINYLESTRADIOL
dc.subjectCHOLESTEROL
dc.subjectMECHANISM
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleENHANCED BILIARY-EXCRETION OF CANALICULAR MEMBRANE ENZYMES IN ETHYNYLESTRADIOL-INDUCED CHOLESTASIS - EFFECTS OF URSODEOXYCHOLIC ACID ADMINISTRATION
dc.typeartículo
dc.volumen50
sipa.codpersvinculados99016
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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