Pioglitazone prevents hepatic steatosis, fibrosis, and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet.
Non-alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis have a risk of development of hepatocellular carcinoma. Peroxisome proliferator-activated receptor (PPAR) gamma ligand has recently been reported to have improved the condition of patients with NASH. The aim of this study was to investigate whether pioglitazone, a PPARgamma ligand, has any influence on the animal model of NASH as well as isolated hepatic stellate cells. In vivo, the effects of pioglitazone were examined using the choline-deficient L-amino acid-defined (CDAA)-diet liver fibrosis model. After two weeks, pioglitazone improved hepatic steatosis, prevented liver fibrosis, and reduced preneoplastic lesions in the liver after 10 weeks. Pioglitazone reduced the expression of TIMP-1 and TIMP-2 mRNA without changing MMP-13 mRNA expression compared to the liver fed a CDAA diet alone. In vitro, pioglitazone prevented the activation of hepatic stellate cells resulting in reducing the expression of type I procollagen, MMP-2, TIMP-1, and TIMP-2 mRNA with increased MMP-13 mRNA expression. These results indicate that pioglitazone may be one of the candidates for the benefit drugs for the liver disease of patients with NASH.
Kawaguchi
Kotaro
K
Department of Gastroenterology and Hepatology, School of Medicine, Yamaguchi University, Minami-Kogushi 1-1-1 Ube, Yamaguchi 755-8505, Japan.
Sakaida
Isao
I
Tsuchiya
Masako
M
Omori
Kaoru
K
Takami
Taro
T
Okita
Kiwamu
K
D000596:Amino Acids; D000821:Animal Feed; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D002796:Choline Deficiency / Q000150:complications*; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D005355:Fibrosis; D005982:Glutathione Transferase / Q000096:biosynthesis; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D009929:Organ Size; D000077205:Pioglitazone; D011347:Procollagen / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D000596:Amino Acids; D015415:Biomarkers; D011347:Procollagen; D012333:RNA, Messenger; D045162:Thiazolidinediones; D019714:Tissue Inhibitor of Metalloproteinases; D014280:Triglycerides; D005982:Glutathione Transferase; D020782:Matrix Metalloproteinases; D000077205:Pioglitazone