PPARα ligands activate antioxidant enzymes and suppress hepatic fibrosis in rats

被引：179

作者：

Toyama, T ^{[1
]}

Nakamura, H ^{[1
]}

Harano, Y ^{[1
]}

Yamauchi, N ^{[1
]}

Morita, A ^{[1
]}

Kirishima, T ^{[1
]}

Minami, M ^{[1
]}

Itoh, Y ^{[1
]}

Okanoue, T ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Kyoto, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 324卷 / 02期

关键词：

hepatic fibrosis; PPAR alpha; Wy-14,643; fenofibrate; oxidative stress; catalase; hydrogen peroxide; thioacetamide;

D O I：

10.1016/j.bbrc.2004.09.110

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Oxidative stress is a major pathogenetic factor in hepatic fibrosis. Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor which is known to affect oxidative stress and PPARalpha. ligands may have rescue effects on hepatic fibrosis. We tested this hypothesis using rat thioacetamide (TAA) models of liver cirrhosis. Rats were given intraperitoneal injection of TAA and treated with a diet containing one of the two PPARa ligands, Wy-14,643 (WY) or fenofibrate. WY treatment dramatically reduced hepatic fibrosis and also prevented the inhibition catalase of mRNA expression caused by TAA. Correspondingly, catalase activity increased in the TAA + WY group but decreased in the control TAA group. The antifibrotic action of fenofibrate in the TAA model was comparable with that of WY. PPARalpha ligands have an antifibrotic action in the rat TAA model of liver cirrhosis, probably due to an antioxidant effect of enhanced catalase expression and activity in the liver. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：697 / 704

页数：8

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