RESUMO
The effects of tetrahydrofuran (THF) on rat liver microsomes in vitro and in vivo were opposite. In vitro THF inhibited the p-nitrophenol (PNP) hydroxylase activity of microsomes from control rats and from rats treated with PB, acetone, and isoniazide--by 50, 20, 60, and 80%, respectively. THF inhibited dimethylnitrosamine (NDMA) demethylation in control and induced microsomes in a lesser degree. THF increased the total cytochrome P-450 content as well as the contents of cytochromes P-450IIE1 and P-450IIB1/B2. The activities of PNP-hydroxylation and NDMA-demethylation increased also, whereas the PR-dealkylation activity was unchanged. An increase in the THF dose caused inhibition of the rat liver microsomal monooxygenase system.
Assuntos
Furanos/farmacologia , Microssomos Hepáticos/efeitos dos fármacos , Oxigenases de Função Mista/metabolismo , Acetona/farmacologia , Animais , Indução Enzimática , Isoniazida/farmacologia , Masculino , Microssomos Hepáticos/enzimologia , Oxigenases de Função Mista/antagonistas & inibidores , Oxigenases de Função Mista/biossíntese , Fenobarbital/farmacologia , Ratos , Ratos WistarRESUMO
It has been found that the Soviet anticonvulsant drug Benzonal is an inducer of the liver cytochrome P-450 of the phenobarbital type. The drug causes formation of the cytochrome P-450 form which is immunologically identical to the phenobarbital inducible form of the hemoprotein with identical molecular mass determined with the SDS-gel electrophoresis method in PAAG. The microsomes, obtained from the rats treated with Benzonal display increased rates of metabolism of 7-pentoxiresorufin and 16 beta-hydroxylation of androstenedione which are specific substrates for the cytochrome P-450b.