PMID- 15573910
OWN - NLM
STAT- MEDLINE
DCOM- 20041221
LR  - 20190721
IS  - 0163-2116 (Print)
IS  - 0163-2116 (Linking)
VI  - 49
IP  - 10
DP  - 2004 Oct
TI  - Effect of losartan, an angiotensin II antagonist, on hepatic fibrosis induced by 
      CCl4 in rats.
PG  - 1589-94
AB  - In addition to regulating blood pressure and body fluid homeostasis, the 
      renin-angiotensin system (RAS) is also involved in hepatic fibrogenesis. We aimed 
      to investigate the effect of losartan, an angiotensin II (Ang II) antagonist, on 
      CCl4-induced hepatic fibrosis in rats. Hepatic fibrosis was induced by a 
      subcutaneous injection with 50% CCl4 in Sprague-Dawley rats. The amount of CCl4 
      administered was 1 mg/kg. Alanine aminotransferase (ALT) and aspartate 
      aminotransferase (AST) levels in plasma and hydroxyproline (Hyp) contents in 
      liver tissue were assayed by spectrophotometry. Hyaluronic acid (HA) and 
      procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis 
      factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels 
      in culture supernatants of Kupffer cells (KCs) stimulated with Ang II was 
      determined by ELISA. Liver samples collected after 12 weeks of CCl4 treatment 
      were stained with hematoxylin and eosin, then scored. Losartan (2.5, 5, and 10 mg 
      x kg(-1), ig) and captopril (100 mg x kg(-1), ig) significantly decreased liver 
      and spleen indexes, serum transaminase (AST, ALT) activities, HA and PC III 
      levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. 
      Histopathological scores showed that losartan had an inhibitory effect on the 
      progression of hepatic fibrosis. In in vitro experiments, losartan (1 x 10(-9) - 
      1 x 10(-5) M) significantly reduced TNF-alpha and TGF-beta1 levels in culture 
      supernatants of KCs, but captopril (1 x 10(-5) M) did not. The results showed 
      that losartan significantly inhibited the progression of hepatic fibrosis induced 
      by CCl4, and the inhibitory effect of losartan on hepatic fibrosis might be 
      associated with its ability to inhibit the production of TNF-alpha and TGF-beta1 
      by activated KCs.
FAU - Wei, Yao Hong
AU  - Wei YH
AD  - Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 
      310031, China. yhgwei@hotmail.com
FAU - Jun, Li
AU  - Jun L
FAU - Qiang, Chen Ji
AU  - Qiang CJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Dig Dis Sci
JT  - Digestive diseases and sciences
JID - 7902782
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Angiotensin II Type 1 Receptor Blockers/pharmacology/*therapeutic use
MH  - Animals
MH  - Aspartate Aminotransferases/blood
MH  - Carbon Tetrachloride/toxicity
MH  - Liver Cirrhosis/chemically induced/*drug therapy/physiopathology
MH  - Losartan/pharmacology/*therapeutic use
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transforming Growth Factor beta/biosynthesis
MH  - Transforming Growth Factor beta1
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2004/12/03 09:00
MHDA- 2004/12/22 09:00
CRDT- 2004/12/03 09:00
PHST- 2004/12/03 09:00 [pubmed]
PHST- 2004/12/22 09:00 [medline]
PHST- 2004/12/03 09:00 [entrez]
AID - 10.1023/b:ddas.0000043369.88701.5b [doi]
PST - ppublish
SO  - Dig Dis Sci. 2004 Oct;49(10):1589-94. doi: 10.1023/b:ddas.0000043369.88701.5b.