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Pitavastatin inhibits hepatic steatosis and fibrosis in non‐alcoholic steatohepatitis model rats
Author(s) -
Miyaki Tomokatsu,
Nojiri Shunsuke,
Shinkai Noboru,
Kusakabe Atsunori,
Matsuura Kentaro,
Iio Etsuko,
Takahashi Satoru,
Yan Ge,
Ikeda Kazuo,
Joh Takashi
Publication year - 2011
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2010.00769.x
Subject(s) - steatosis , steatohepatitis , cirrhosis , pitavastatin , medicine , hepatic fibrosis , fibrosis , endocrinology , hepatocellular carcinoma , fatty liver , gastroenterology , statin , disease
Aim: Non‐alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis are at risk of developing hepatocellular carcinoma. Statins, 3‐hydroxy‐3‐methyglutaryl‐coenzyme A reductase inhibitors, are well known to reduce low‐density lipoprotein cholesterol and reduce the incidence of coronary heart disease and other major vascular events by anti‐inflammatory and antifibrotic effects, and antiproliferative properties in colorectal cancers have also been reported. Recently, statins have been reported to improve hepatic steatosis; however, the effect on fibrosis is controversial. Methods: The effects of pitavastatin (one of the strongest statins) were examined using a choline‐deficient L‐amino acid‐defined (CDAA) diet liver fibrosis model. Results: Pitavastatin significantly attenuated increases in serum aspartate aminotransferase, alanine aminotransferase, hepatic steatosis, oxidative stress, pre‐neoplastic lesions (glutathione S‐transferase placental form‐positive lesions), expression of cytokines, such as tumor necrosis factor‐α and transforming growth factor‐β1, and the expression of tissue inhibitor of metalloproteinase‐1, tissue inhibitor of metalloproteinase‐2 and type I procollagen genes followed by attenuating fibrosis of the liver of CDAA‐fed rats. Conclusion: These results indicate that pitavastatin may inhibit steatosis, hepatic fibrosis and carcinogenesis in rat model of NASH.