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Nie L, Imamura M, Itoh H, Ueno H: Pitavastatin enhances the anti-fibrogenesis effects of candesartan, an angiotensin II receptor blocker, on CCl4-induced liver fibrosis in rats. J UOEH. 2004 Jun 1;26(2):165-77.
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. |
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