Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Enzyme Inhib Med Chem ; 20(3): 219-26, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16119191

RESUMO

The effect of the titled tetralone as a retinoic acid metabolism blocking agent (RAMBA) in vivo in comparison with ketoconazole, a well known cytochrome P450 inhibitor, was studied. Development of a HPLC/MS/MS method for the quantification of retinoic acid levels extracted from rat plasma was used to demonstrate that ketoconazole and the tetralone (100 mg/kg) enhanced the endogenous plasma concentration of retinoic acid. Levels of retinoid were raised from a control value of 0.11 to 0.15 and 0.17 ng/mL after treatment with tetralone and ketoconazole respectively showing that the tetralone and ketoconazole lead to comparable effects, indicating an inhibitory activity of the tetralone on retinoic acid metabolism.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Isotretinoína/sangue , Naftalenos/farmacologia , Espectrometria de Massas por Ionização por Electrospray/métodos , Tretinoína/sangue , Animais , Isotretinoína/química , Cetoconazol/metabolismo , Cetoconazol/farmacologia , Masculino , Espectrometria de Massas , Ratos , Ratos Endogâmicos WF , Tetralonas/metabolismo , Tetralonas/farmacologia , Tretinoína/química
2.
J Steroid Biochem Mol Biol ; 96(3-4): 259-70, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15985365

RESUMO

Aldosterone plays a key role in salt and water homeostasis but is also involved in the development and progression of congestive heart failure and myocardial fibrosis. As a new pharmacological strategy for the treatment of these diseases, we propose the inhibition of the key enzyme of mineralcorticoid formation, CYP11B2 (aldosterone synthase). For studies of the effects of CYP11B2 inhibitors on the adrenal cortex, we selected the NCI-H295R cell line which expresses most of the key enzymes necessary for steroidogenesis. To evaluate this cell line as a test system for effects and side effects of CYP inhibitors, we established assays using radiolabeled substrates of CYP11B2 and CYP11B1 and subsequently tested a series of CYP11B2 inhibitors including the CYP19 inhibitor fadrozole. Fadrozole and compounds 6, 9 and 10 were more potent towards CYP11B2 compared to CYP11B1 with IC(50) values in the nanomolar range. To analyze their overall effect, the formation of steroids in the cell culture supernatant was monitored. All compounds led to a concentration-dependent reduction of the aldosterone secretion but also reduced the formation of cortisol and androgens. In conclusion, the H295R cell line is a suitable tool for the prediction of overall side effects of CYP11B2 inhibitors on steroidogenesis.


Assuntos
Linhagem Celular Tumoral , Citocromo P-450 CYP11B2/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Esteroide 11-beta-Hidroxilase/antagonistas & inibidores , Córtex Suprarrenal/citologia , Córtex Suprarrenal/efeitos dos fármacos , Córtex Suprarrenal/enzimologia , Aldosterona/metabolismo , Inibidores da Aromatase/farmacologia , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Fadrozol/farmacologia , Humanos , Esteroides/análise , Esteroides/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...