EJMS

Abstract

Liver fibrosis is considered as a progressive pathological process involving multiple cellular and molecular events that lead to deposition of excess matrix proteins in the extracellular space. When this process is combined with ineffective regeneration and repair, there is increasing distortion of the normal liver architecture, and the end result is cirrhosis. Emerging anti-fibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, the mechanisms underlying the anti-fibrotic effect on liver fibrosis remain unclear. The aim of the present study was to investigate the underlying mechanisms of anti-fibrotic effect of angiotensin converting enzyme inhibitor (ACEI) on experimental liver fibrosis induced by carbon tetrachloride (CCl₄). 35 white albino male rats of 150-200 gm average weight were randomly divided into three groups, Group I: The control group (n = 10), Group II: CCl₄ injected rats without any treatment (n = 10) and Group III: CCl₄ injected rats that received an ACEI, perinodopril, dissolved in distilled water, 6mg/kg/day for 4 weeks (n = 15). Venous blood was collected from retro-orbital vein for serum separation for assay of liver functions. Liver tissue was subdivided into three portions for: pathological examination, estimation of transforming growth factor-beta1 (TGF-ß₁) and matrix metalloproteinase-9 (MMP-9) by ELISA and expression of nuclear factor- kappa beta (NF-?B) in a trial to understand the mechanism underlying the anti-fibrotic effect of ACEI. Tissue TGF-ß₁, MMP-9 and NF-?B were significantly higher in CCl₄ group (group II) compared with control group (group I) and they were decreased significantly with administration of ACEI with CCl₄ (group III). In conclusion, ACEI attenuates the progression of hepatic fibrosis induced by CCl₄ by reducing expression of NF-?B, TGF-ß₁, and MMP-9.