Pitavastatin enhances the anti-fibrogenesis effects of candesartan, an angiotensin II receptor blocker, on CCl4-induced liver fibrosis in rats.
It has been shown that a statin (3-hydroxy-3-methyl-glutaryl coenzyme reductase inhibitor) enhances a suppressive effect of angiotensin II type 1 receptor (AT1-R) blocker (ARB) on injury-induced transforming growth factor (TGF)-beta expression in kidneys. We have shown that TGF-beta plays a crucial role in the development of liver fibrosis. In this study, we tested whether a combinatory use of a statin (pitavastatin) and an ARB (candesartan) may further inhibit liver fibrogenesis in carbon tetrachloride (CCl4)-treated rats. Candesartan (8 mg/kg/day) significantly suppressed injury-induced TGF-beta 1 expression in livers, and attenuated fibrogenesis, as evaluated by masson-trichrome staining and hydroxyproline content in livers. Pitavastatin (2 mg/kg/day) alone did not affect liver fibrogenesis. However, it enhanced significantly the suppressive effects of candesartan on TGF-beta 1 expression and fibrogenesis. Although we do not know the underlying molecular mechanisms at this moment, these results suggest that a combinatory use of a statin and an ARB may confer beneficial effects on human liver fibrogenesis.
Nie
Lianbo
L
Department of Biochemistry, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Imamura
Michio
M
Itoh
Hideaki
H
Ueno
Hikaru
H
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D002251:Carbon Tetrachloride; D003864:Depression, Chemical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D002251:Carbon Tetrachloride; C108475:pitavastatin; C081643:candesartan