RESUMEN
Using a synthetic substitute, Ultroser HY, for fetal bovine serum to supplement a classical RPMI 1640 culture medium produced changes in the properties of sensitive and of multidrug-resistant K 562 cells. Though no morphological changes were found, a statistically significant decrease in doubling-time was noted. Plasma membranes were more rigid, as reflected by an increase in the order parameter values. Adriamycin cytotoxicity was decreased, as shown by an increase in IC 50 values. The THP-adriamycin uptake, monitored by fluorimetry, was diminished even when the revertant agent verapamil was added. Moreover, the apparent number of Pgp 170 molecules per cell was lower for resistant cells grown with Ultroser HY. Thus Pgp 170 was not involved in the MDR increase induced by Ultroser HY. In conclusion, it must be kept in mind that environmental factors such as media chemical composition influence the MDR phenomenon and that environmental factors may also influence the MDR phenomenon in clinical situations.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antibióticos Antineoplásicos/farmacocinética , Medios de Cultivo/farmacología , Doxorrubicina/análogos & derivados , Resistencia a Múltiples Medicamentos , Animales , Antibióticos Antineoplásicos/farmacología , Bovinos , División Celular/efectos de los fármacos , Línea Celular/efectos de los fármacos , Línea Celular/patología , Medios de Cultivo/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Humanos , Fluidez de la Membrana/efectos de los fármacos , Verapamilo/farmacologíaRESUMEN
As little work has dealt with the antihyperglycemic property of benfluorex at the hepatocyte level, we studied the effects of its main metabolites, S422 and S1475, on membrane fluidity and on insulin binding, internalization and action in healthy rat hepatocytes. Both metabolites were effective fluidizing agents. Neither one affected insulin binding. Only S422 favored the bound insulin-receptor internalization process. The metabolites produced no change in basal alpha-aminoisobutyric acid uptake. Only S422 promoted the insulin-stimulated alpha-aminoisobutyric acid uptake in a dose-dependent way. Therefore, our study demonstrated that: (i) the effects of S422 on insulin-related processes in isolated hepatocytes were direct, specific and not due to any membrane fluidizing mechanism; (ii) S422 improved hepatocyte response to insulin at a post-binding level. These results in vitro give an additional explanation, at the cellular level, of the benefit of benfluorex treatment for non insulin-dependent diabetes patients.