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Endothelial nitric oxide synthase is a critical factor in experimental liver fibrosis
Author(s) -
Leung TungMing,
Tipoe George L.,
Liong Emily C.,
Lau Thomas Y.H.,
Fung ManLung,
Nanji Amin A.
Publication year - 2008
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.1365-2613.2008.00590.x
Subject(s) - enos , nitric oxide synthase , nitric oxide , arginine , oxidative stress , endocrinology , medicine , chemistry , fibrosis , endothelial nos , liver injury , biochemistry , amino acid
Summary Reduced expression of endothelial nitric oxide synthase (eNOS) in chronic liver disease can reduce hepatic perfusion and accelerate fibrosis. The relationship between eNOS expression and liver fibrogenesis remains unclear. We investigated whether l ‐arginine attenuated chronic liver fibrosis through eNOS expression. Chronic liver injury was induced by administration of carbon tetrachloride (CCl 4 ) to mice for 8 weeks. 5‐Methylisothiourea hemisulphate (SMT), an iNOS inhibitor, or l ‐arginine, a NOS substrate were injected subcutaneously. CCl 4 ‐induced hepatotoxicity, oxidative stress and accumulation of collagen were detected in the liver. The expression levels of inducible NOS (iNOS) and nuclear factor kappa‐B (NF‐κB) activity in the liver after CCl 4 treatment were increased but eNOS expression and activator protein‐1 (AP‐1) activity were decreased. Both SMT and l ‐arginine effectively reduced CCl 4 induced oxidative stress and collagen formation, but l ‐arginine showed a significantly greater suppression of collagen formation, iNOS expression and NF‐κB activity. l ‐Arginine also restored the level of eNOS and AP‐1 activity. l ‐Arginine was more effective than SMT in suppressing liver fibrosis. l ‐Arginine might improve NO production which facilitates hepatic blood flow and thus retards liver fibrogenesis. Our results showed that the reduced eNOS expression in CCl 4 ‐treated mice was reversed by l ‐arginine. Furthermore, l ‐arginine also reversed the reduced AP‐1 activity, an eNOS promoter.