Effect of pioglitazone on endotoxin-induced decreases in hepatic drug-metabolizing enzyme activity and expression of CYP3A2 and CYP2C11
作者： Hiroaki Kanazawa , Ryujiro Suzuki , Kenji Takagi , Kenzo Takagi , Takaaki Hasegawa
DOI: 10.1016/J.EJPHAR.2004.07.079
关键词:
摘要: It has been reported that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands ameliorate the expression of inducible nitric oxide synthase (iNOS) by endotoxin. In present study, we investigated effect pioglitazone, a potent PPAR-gamma ligand, on endotoxin-induced reduction hepatic drug-metabolizing enzyme activity and down-regulation cytochrome P450 (CYP) 3A2 CYP2C11 proteins in rats. Endotoxin (1 mg/kg) significantly decreased vivo, as represented systemic clearance antipyrine protein levels CYP3A2 24 h after intraperitoneal injection. Pretreatment with pioglitazone (10 mg/kg, 4 times at 10-min intervals) protected decreases CYP3A2, but not CYP2C11, no biochemical histopathological changes liver. Pioglitazone alone had or CYP2C11. overexpression iNOS liver, overproduction (NO) plasma. is unlikely protective against liver due to inhibition NO.
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