RESUMEN
The induction of ferrochelatase activity by phenobarbital and its potentiation by dibutyryl cAMP assayed in normal rat hepatocytes are associated with increased activity of ferrochelatase mRNA. Glucose inhibits this stimulatory effect. This inhibition can be reversed with increasing concentrations of dibutyryl cAMP. The inducing effect exerted by phenobarbital on the activity of ferrochelatase mRNA in diabetic hepatocytes is greater than that observed in normal cells. This enhanced response in diabetic rat hepatocytes is neither potentiated by adding dibutyryl cAMP nor repressed by glucose. The absence of a glucose effect persists even when the endogenous cAMP content is lowered to normal levels. The results obtained in this study are consistent with those reported in other published studies of ferrochelatase activity. This adds more experimental evidence to support the concept that ferrochelatase is inducible. The results obtained suggest that ferrochelatase is more susceptible to induction with phenobarbital in diabetic rat hepatocytes than in normal rat hepatocytes.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Ferroquelatasa/biosíntesis , Regulación de la Expresión Génica , Hígado/metabolismo , ARN Mensajero/biosíntesis , Animales , Bucladesina/farmacología , Inducción Enzimática/efectos de los fármacos , Glucosa/farmacología , Masculino , Fenobarbital/farmacología , Ratas , Ratas EndogámicasRESUMEN
The present work demonstrates that phenformin exerted an inducing effect on delta-aminolevulinic acid synthase (ALA-S) and ferrochelatase activities and on cytochrome P-450 content in isolated hepatocytes from rats with experimental diabetes. Similar results were obtained with respect to ALA-S activity and cytochrome P-450 content when chlorpropamide was used. The inducing effect exerted by allylisopropylacetamide (AIA) on ALA-S and ferrochelatase activities in diabetic hepatic cells was markedly greater than that observed in normal hepatocytes. This stimulatory response was not enhanced by adding dibutyryl cyclic AMP (cAMP). When phenformin was added to isolated rat hepatocytes of normal rats, induction of ALA-S and ferrochelatase activities and cytochrome P-450 content was observed only in the presence of added dibutyryl cAMP. Addition of chlorpropamide to this in vitro system did not exert an inducing effect on the same enzymes even in the presence of dibutyryl cAMP. The present results add more experimental evidence about the lability of the heme pathway of diabetic hepatocytes.
Asunto(s)
5-Aminolevulinato Sintetasa/biosíntesis , AMP Cíclico/biosíntesis , Sistema Enzimático del Citocromo P-450/biosíntesis , Diabetes Mellitus Experimental/enzimología , Ferroquelatasa/biosíntesis , Liasas/biosíntesis , Fenformina/farmacología , Alilisopropilacetamida/farmacología , Animales , Bucladesina/farmacología , Clorpropamida/farmacología , Inducción Enzimática/efectos de los fármacos , Técnicas In Vitro , Plomo/farmacología , Hígado/enzimología , Masculino , RatasRESUMEN
Apos considerações preliminares sobre as molestias decorrentes de alterações do metabolismo as porfirinas que se traduzem clinicamente por alterações cutaneas digestivas, neurologicas e psiquicas é apresentado o cado de uma paciente portadora de forma aguda de porfiria.Trata-se de paciente com 29 anos de idade com antecedentes de dores nos membros e colicas abdominais quer apresentou bruscamente quadro de paralisia motora dos quatros membros e de alguns nervos cranianos. O teste de watson e schwartz revelou a presença de profobilinogenio na urina o que firmou o diagnostico. Apos um ano de internação durante o qual a molestia evoluiu por surtos a paciente faleceu tendo o exame anatomo patologico do sistema nervoso revelado alterações degenerativas das celulas motoras das pontas anteriores da medula e de nucleo motores do tronco encefalico.