Abstract

ANTI-APOPTOTIC AND ANTIFIBROTIC MECHANISMS OF TELMISARTAN AND LOSARTAN IN THIOACTAMIDE-INDUCED LIVER FIBROSIS IN RATS

Mervat Z. Mohamed*, Entesar F. Amin, Nashwa F. El-Tahawy, Rehab K. Mohammed and Aly M. Abdelrahman

ABSTRACT

Liver fibrosis is a common pathological consequence of a variety of chronic stimuli, including viral, autoimmune, drug induced, cholestatic and metabolic diseases that present worldwide. Angiotensin II and PPARγ play major roles in the pathogenesis of liver fibrosis. Telmisartan is a unique among angiotensin receptor blockers (ARBs) that has peroxisome proliferative receptor gamma (PPARγ) agonism. The aim of this study was to investigate the effect of oral administration of 10 mg/kg of either telmisartan or losartan in liver fibrosis-induced by thioacetamide (TAA) in rats via a dose of (50 mg/kg, twice weekly) for 6 weeks. To evaluate the level of hepatic damage and the potential protecting effects, liver function tests as alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin and albumin as well as hepatic oxidative stress parameters malondialdehyde (MDA), total nitrite and nitrate and superoxide dismutase (SOD) were assessed. Liver fibrosis was evaluated by histological examination using masson trichrome stain as well as immuno-histochemical expression of alpha smooth muscle actin (α SMA), inducible nitric oxide synthase (iNOS), caspase 3 and tissue inhibitor metalloprotinase (TIMP-1) expression on hepatic tissue. Results revealed comparable antifibrotic effects of telmisartan and losartan, based on decreasing oxidative damage induced by TAA, inactivation of HCSs, decreasing caspase 3 expression and an antagonistic mechanistic pathways. While, telmisartan increased TIMP-1 and decreased iNOS expression, losartan increased iNOS and decreased TIMP-1 expression in hepatic tissue. In conclusion, both telmisartan and losartan successfully reversed TAA-induced liver fibrosis, through antioxidative, anti-apoptotic and anti-fibrotic mechanisms.

Keywords: Telmisartan; Liver fibrosis; Thioacetamide; iNOS; caspase-3; TIMP1.