Anti-fibrogenic effects of captopril and candesartan cilexetil on the hepatic fibrosis development in rat. The effect of AT1-R blocker on the hepatic fibrosis.
OBJECTIVE
Angiotensin converting enzyme (ACE) and angiotensin II (AT-II) have been suggested to play an important role in liver fibrogenesis. There is a significant relationship between inheritance of hightened expression of transforming growth factor beta1 (TGF-beta1) and AT-II and the development of progressive hepatic fibrosis. The purpose of this study was to investigate the effects of captopril, an ACE inhibitor and candesartan cilexetil, an AT-II type 1 receptor (AT1-R) blocker, on liver fibrosis induced in rats by carbon tetrachloride (CCl4) administration.


METHODS
rats were divided into 4 experimental groups: The first group was given CCl4 alone; the second was given both CCl4 and captopril (100 mg x kg(-1) x day(-1)); the third was given both CCl4 and candesartan cilexetil (8 mg x kg(-1) x day(-1)); fourth group was given 0.9% NaCl only. Seven weeks after initiating the treatment, indices of fibrosis were assessed.


RESULTS
Candesartan cilexetil treatment significantly reduced the fibrosis development. These inhibitory effects were not observed in the captopril-treated group. The mean fibrosis score was significantly lower in the CCl4/candesartan group compared with the group applied to CCl4 alone and the group applied to CCl4/captopril. Similarly, the number of alpha-smooth muscle actin positive cells was markedly suppressed by candesartan treatment.


CONCLUSIONS
The results suggest that AT-II plays a pivotal role in hepatic fibrogenesis and candesartan significantly attenuates the progression of liver fibrosis. This drug may provide an effective new strategy for prevention of liver fibrosis. Its effectiveness should be investigated in chronic liver disease associated with progressive fibrosis.
Tuncer
Ilyas
I
Department of Gastroenterology, Yuzuncu Yil University Medical Faculty, Van, Turkey. iltuncer@yahoo.com
Ozbek
Hanefi
H
Ugras
Serdar
S
Bayram
Irfan
I
D000199:Actins / Q000032:analysis; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D002216:Captopril / Q000627:therapeutic use*; D002251:Carbon Tetrachloride / Q000633:toxicity; D002452:Cell Count; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
D000199:Actins; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D002216:Captopril; D002251:Carbon Tetrachloride; C081643:candesartan