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Losartan Protection Against CCL4 Induced Hepatic Fibrosis Involves Changes In Adhesion Molecules and Inflammatory Markers
Author(s) -
Nassar Noha N,
El Wakeel Sara A.,
El Sayed Moushira I.,
ElDenshary Ezzeldein S. M.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1093.17
Subject(s) - losartan , ccl4 , hepatic fibrosis , tbars , fibrosis , angiotensin ii , medicine , pharmacology , endocrinology , chemistry , receptor , oxidative stress , carbon tetrachloride , lipid peroxidation , organic chemistry
The role of Angiotensin II (AgII) receptor blockers in the limitation of progression of hepatic fibrosis remains yet to be explored. In the current study we investigated the anti‐inflammatory, antioxidant and antifibrotic effect of 3 ascending doses (5,10, and 20 mgkg −1 ) of an agiotensin II receptor blocker losartan (LOS) in a model of CCl4 induced hepatic fibrosis. To this end, 60 male Wistar rats were divided into 5 groups; Gp I received olive oil and served as vehicle, Gp II received CCL4 (3.1gkg −1 ,i.p in olive oil 1:1) twice weekly for 8 weeks. GP III, IV and V received CCL4 + LOS 5, 10 and 20mgkg −1 , p.o, respectively. LOS was given one hour before CCL4 insult daily for 10 weeks starting from the first day of CCL4 administration.LOS (5,10 and 20 mgkg − 1 ) significantly reduced serum transaminases (ALT, AST), hepatic content of TBARS,NO, MPO, ICAM‐1 and TNF‐α in a dose dependent manner. LOS significantly raised the levels of hepatic NPSH and TAC in a dose dependent manner. The results showed that losartan has improved CCL4 induced hepatic fibrosis throughout its anti‐inflammatory and antioxidant mechanisms. These biochemical changes correlated positively with histopathological changes induced by CCL4.