HYPOLIPEMIC DRUGS ARE ACTIVATED TO ACYL-COA ESTERS IN ISOLATED RAT HEPATOCYTES - DETECTION OF DRUG ACTIVATION BY HUMAN LIVER HOMOGENATES AND BY HUMAN PLATELETS

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dc.contributor.authorBRONFMAN, M
dc.contributor.authorMORALES, MN
dc.contributor.authorAMIGO, L
dc.contributor.authorORELLANA, A
dc.contributor.authorNUNEZ, L
dc.contributor.authorCARDENAS, L
dc.contributor.authorHIDALGO, PC
dc.date.accessioned2025-01-23T19:22:08Z
dc.date.available2025-01-23T19:22:08Z
dc.date.issued1992
dc.description.abstractThe formation of acyl-CoA esters of the hypolipidaemic peroxisome proliferators clofibric acid, ciprofibrate and nafenopin was studied in isolated rat hepatocytes. The concentration of ciprofibroyl-CoA in the liver of ciprofibrate-treated rats was in the range of 10-30-mu-M. The three drugs formed acyl-CoA esters when incubated with isolated hepatocytes. Their formation was saturable and reached a plateau after 30 min incubation. Maximal intracellular concentrations of ciprofibroyl-CoA and clofibroyl-CoA (100-mu-M and 55-mu-M respectively) were attained at 0.5 mM of the free drugs in the incubation medium, whereas for nafenopin-CoA, the maximal intracellular concentration (9-mu-M) was reached at 1 mM-nafenopin. At low concentrations of the hypolipidaemic compounds in the incubation medium a significant proportion of the total intracellular drug was present as its acyl-CoA ester (25-35% for ciprofibrate). When isolated hepatocytes were incubated with a ciprofibrate concentration comparable with that observed in the blood of drug-treated rats (0.1 mM), ciprofibroyl-CoA attained an intracellular concentration similar to that previously observed in the liver of treated rats. The formation of ciprofibroyl-CoA by isolated rat hepatocytes was stimulated by the addition of carnitine and partially inhibited by the addition of palmitate. Further, it was shown that human liver homogenates synthesized ciprofibroyl-CoA at a rate similar to that observed for rat liver homogenates. Solubilized human platelets also formed ciprofibroyl-CoA, although at a rate two orders of magnitude lower than that of liver. The results support the view that acyl-CoA esters of hypolipidaemic peroxisome proliferators may be the pharmacologically active species of the drugs.
dc.fuente.origenWOS
dc.identifier.issn0264-6021
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/98971
dc.identifier.wosidWOS:A1992HV22300041
dc.language.isoen
dc.pagina.final295
dc.pagina.inicio289
dc.revistaBiochemical journal
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleHYPOLIPEMIC DRUGS ARE ACTIVATED TO ACYL-COA ESTERS IN ISOLATED RAT HEPATOCYTES - DETECTION OF DRUG ACTIVATION BY HUMAN LIVER HOMOGENATES AND BY HUMAN PLATELETS
dc.typeartículo
dc.volumen284
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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