The mechanism of the rat liver cytochrome P4502E1 inhibition by the synthetic prostanoids of A-type.
Prostaglandins Other Lipid Mediat
; 89(1-2): 16-9, 2009 Jun.
Article
en En
| MEDLINE
| ID: mdl-19464662
ABSTRACT
AIM:
The elucidation of mechanism of A-type synthetic prostanoids inhibitory action on microsomal cytochrome P(450)2E1 (CYP2E1) from rat liver activity was carried out.RESULTS:
Analogs U-34 and U-26 in a final concentration of 1 x 10(-5)M inhibited CYP2E1 activity by 93% and 46%, respectively; however natural prostaglandins had no effect. These synthetic prostanoids of A-type (5 x 10(-8) to 10(-4)M) inhibited chlorzoxazone hydroxylation in a dose-dependent manner while IC(50)=7.1 x 10(-7)M and 8.0 x 10(-7)M for U-26 and U-34, respectively. The curves of CYP2E1 activity in the presence of different concentrations of chlorzoxazone and varying concentration of prostanoids were hyperbolic. Double-reciprocal plots of these results 1/V=f(1/S) indicated that prostanoids inhibit CYP2E1 through a competitive mechanism with particular effect.CONCLUSION:
CYP2E1 is a target for A-type prostanoids, possessing 2-oxo-4-amino-oct-3(E)-enyl in alpha- or omega-chain, which are able to inhibit its action through a competitive mechanism.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Prostaglandinas
/
Inhibidores Enzimáticos
/
Inhibidores del Citocromo P-450 CYP2E1
/
Hígado
Límite:
Animals
Idioma:
En
Revista:
Prostaglandins Other Lipid Mediat
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Belarús