The mechanism of the rat liver cytochrome P4502E1 inhibition by the synthetic prostanoids of A-type.
OBJECTIVE
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.


CONCLUSIONS
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.
Hubich
A I
AI
Department of Biochemistry, Belarussian State University, Minsk, Belarus. Hubich_Oksana@tut.by
Lakhvich
F A
FA
Sholukh
M V
MV
D000818:Animals; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008861:Microsomes / Q000201:enzymology; D011453:Prostaglandins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins