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Aliskiren attenuates chronic carbon tetrachloride–induced liver injury in mice
Author(s) -
Lee KueiChuan,
Chan CheChang,
Yang YingYing,
Hsieh YunCheng,
Huang YiHsiang,
Lin HanChieh
Publication year - 2012
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2012.02725.x
Subject(s) - aliskiren , carbon tetrachloride , inflammation , renin–angiotensin system , medicine , liver injury , fibrosis , angiotensin ii , renin inhibitor , endocrinology , pharmacology , hepatic stellate cell , apoptosis , receptor , chemistry , biochemistry , organic chemistry , blood pressure
Eur J Clin Invest 2012; 42 (12): 1261–1271 Abstract Background Increased angiotensin II (Ang II) plays an important role in liver inflammation and fibrogenesis. Chronic administration of aliskiren, a newly developed direct renin inhibitor, decreases Ang II in the hypertensive patients and animals. Aims Our study aims to evaluate the possible protective effects of chronic administration of aliskiren in a chronic liver injury model. Methods C57BL6 mice were injected intraperitoneally with carbon tetrachloride (CCl 4 ) to induce chronic liver injury. The injured mice were randomly assigned to aliskiren‐treated (25 mg/kg per day for 2 weeks, the CCl 4 + Ali group) or untreated group (the CCl 4 group). Mice without CCl 4 and aliskiren administration served as the normal control. Results In the CCl 4 ‐injured mice, aliskiren attenuated liver inflammation and fibrosis. The levels of hepatocyte apoptosis, lipid peroxidation production, the activation of hepatic stellate cells and Kupffer cells, hepatic expression of p47 phox, inflammatory mediators and profibrotic markers were reduced in the CCl 4 + Ali group. Furthermore, aliskiren decreased Ang II, activated the renal expression of renin, but down‐regulated the hepatic expression of renin and renin receptor in the CCl 4 ‐injected mice. Conclusions Aliskiren attenuates chronic liver injury in the CCl 4 ‐treated mice by reducing Ang II. Direct renin inhibition may serve as a potential treatment for chronic liver injury.