Assuntos
Oxigenases de Função Mista/análise , Pâncreas/fisiologia , Animais , Benzoflavonas/farmacologia , Diabetes Mellitus Experimental/enzimologia , Indução Enzimática/efeitos dos fármacos , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Oxigenases de Função Mista/biossíntese , Oxigenases de Função Mista/efeitos dos fármacos , Pancreatectomia , Fenobarbital/farmacologia , Ratos , Ratos Endogâmicos , Fatores de Tempo , beta-NaftoflavonaRESUMO
In experiments on male Wistar rats it has been found that nifedipine applied in a dose of 10 mg/kg body weight i.p. daily for 20 days did not significantly increase the total amount of cytochrome P-450 but markedly increased the 7 alpha-, 16 beta- and 6 beta-hydroxylation of androstenedione in liver microsomes, suggesting the induction of cytochromes P-450a, P-450b and P-450p respectively. The induction of cytochrome P-450b was also confirmed immunochemically with polyclonal antibodies against cytochrome P-450b/e.
Assuntos
Sistema Enzimático do Citocromo P-450/biossíntese , Nifedipino/farmacologia , Androstenodiona/metabolismo , Animais , Indução Enzimática/efeitos dos fármacos , Hidroxilação , Masculino , Nifedipino/administração & dosagem , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
The protective effects of alpha-tocopherol, carnosine and their mixture on monooxygenase system during lipid peroxidation in liver microsome membranes were studied. It was shown that for optimal protection effect of cytochrome P-450 system the mixture of water and liposoluble antioxidants is required.
Assuntos
Antioxidantes/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Animais , Carnosina/farmacologia , Microssomos Hepáticos/enzimologia , Oxigenases/metabolismo , Ratos , Ratos Endogâmicos , Solubilidade , Vitamina E/farmacologiaAssuntos
Membranas Intracelulares/metabolismo , Peróxidos Lipídicos/antagonistas & inibidores , Microssomos Hepáticos/metabolismo , Sinaptossomos/metabolismo , Vitamina E/análogos & derivados , Animais , Cromanos/farmacologia , Técnicas In Vitro , Membranas Intracelulares/efeitos dos fármacos , Cinética , Peróxidos Lipídicos/metabolismo , Masculino , Lipídeos de Membrana/antagonistas & inibidores , Lipídeos de Membrana/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade , Sinaptossomos/efeitos dos fármacos , Vitamina E/farmacologiaRESUMO
The efficacy of lipid peroxidation inhibition by the natural antioxidant alpha-tocopherol and 2,2,5,7,8-pentamethyl-6-hydroxy-chromane (PMC), a derivative without hydrocarbon tail, as well as by the synthetic antioxidant 4-methyl-2,6-diterbutyl phenol (BHT) and its phospholipid derivative was studied in the membranes of rat liver microsomes and mitochondria. The presence of hydrocarbon tail in the antioxidant molecule determines the decrease of antioxidant efficiency in biomembranes. PMC and BHT exert a destructive effect on biomembranes, leading to an increase in their permeability to ions. This evidence suggests that the presence of hydrocarbon tail in the molecules of natural antioxidants provides not only for a relatively high antioxidant efficiency but also for a structural stability of biomembranes.
Assuntos
Antioxidantes/farmacologia , Peróxidos Lipídicos/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Animais , Hidroxitolueno Butilado/farmacologia , Cromanos/farmacologia , Depressão Química , Membranas Intracelulares/metabolismo , Masculino , Microssomos Hepáticos/metabolismo , Mitocôndrias Hepáticas/metabolismo , Oxirredução/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade , Vitamina E/farmacologiaAssuntos
Eritromicina/farmacologia , Leucomicinas/farmacologia , Oxigenases de Função Mista/metabolismo , Troleandomicina/farmacologia , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos EndogâmicosAssuntos
Peróxidos Lipídicos/metabolismo , Metais/farmacologia , NADP/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Oxirredução/efeitos dos fármacos , Ratos , Ratos EndogâmicosAssuntos
Corticosteroides/farmacologia , Oxigenases de Função Mista/antagonistas & inibidores , Animais , Citosol/efeitos dos fármacos , Citosol/enzimologia , Desoxicorticosterona/administração & dosagem , Hidrocortisona/administração & dosagem , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Ratos , Ratos EndogâmicosRESUMO
The authors examined systematically the influence of some thiol compounds on the drug metabolism, investigating the effect of potassium ethylxanthogenate, diethyldithiocarbamata, inithiol and penicilamine on the aniline toxicity, methemoglobin formation and aniline-hydroxylase activity. They found that the examined compounds increased aniline toxicity in white male rats. These compounds inhibited aniline-hydroxilase activity. The connection between the increase of the toxicity of aniline under the influence of the examined compounds and their inhibiting action on the metabolism of aniline was discussed.
Assuntos
Compostos de Anilina/toxicidade , Compostos de Sulfidrila/farmacologia , Compostos de Anilina/metabolismo , Anilina Hidroxilase/metabolismo , Animais , Carbonatos/farmacologia , Ditiocarb/farmacologia , Sinergismo Farmacológico , Ativação Enzimática/efeitos dos fármacos , Fígado/enzimologia , Masculino , Metemoglobina/metabolismo , Penicilamina/farmacologia , Ratos , Tionas/farmacologia , Fatores de Tempo , Unitiol/farmacologiaRESUMO
The authors carried out studies on white rats of Wistar strain and investigated some of the mechanisms, metabolic and central, by means of which hydrocortisone affected hexobartital sleep. They established that hydrocortisone in dose of 25 and 50 mg, administered singly, together with hexobarbital or after a 30-minute interval, potentiated hexobarbital sleep significantly. The concentrations of hexobarbital in blood serum and in brain on the 30th minute after its administration were higher in the experimental animals, treated with hexobarbital in comparison with the controls of both sexes. The experiments with determination of the activity of liver microsomal hexobarbital enzymic system showed convincingly a considerable inhibition of enzymic activity (with 53%) of hydrocortisone after 20 minutes after its application in vivo. Subthreshold sreep dose of hexobarbital, determined by the method of Lewy, was lowered than that of the experimental group and higher in the control rats. Hexobarbital concentrations in blood serum and in brain at the moment of waking were lower in experimental animals, treated with hydrocortisone, and higher in the control animals. The obtained results gave foundations to the authors to assume that metabolic and central nervous mechanisms participated in potentiation of hexobarbital sleep.