Literature DB >> 15474484

PPARalpha ligands activate antioxidant enzymes and suppress hepatic fibrosis in rats.

Tetsuya Toyama1, Hideki Nakamura, Yuichi Harano, Norihito Yamauchi, Atsuhiro Morita, Toshihiko Kirishima, Masahito Minami, Yoshito Itoh, Takeshi Okanoue.   

Abstract

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 PPARalpha 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.

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Year:  2004        PMID: 15474484     DOI: 10.1016/j.bbrc.2004.09.110

Source DB:  PubMed          Journal:  Biochem Biophys Res Commun        ISSN: 0006-291X            Impact factor:   3.575


  56 in total

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