title: Aliskiren attenuates chronic carbon tetrachloride-induced liver injury in mice.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Kuei-Chuan
authors.initials: KC
authors.lastname: Lee
authors.forename: Che-Chang
authors.initials: CC
authors.lastname: Chan
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Yang
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Huang
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000209:etiology / Q000517:prevention & control*; D004347:Drug Interactions; D005650:Fumarates / Q000494:pharmacology*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000804:Angiotensin II; D000959:Antihypertensive Agents; D002251:Carbon Tetrachloride; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren