Telmisartan Ameliorates Carbon Tetrachloride-induced Acute Hepatotoxicity in Rats Reem T. Atawia, Ahmed Esmat, Doaa A. Elsherbiny, Ebtehal El-Demerdash Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt Received 28 June 2015; revised 13 January 2016; accepted 24 January 2016 ABSTRACT: This study assessed the potential hepatoprotective effect of telmisartan (TLM), a selective angiotensin II type 1 (AT 1 ) receptor blocker, on carbon tetrachloride (CCl 4 )-induced acute hepatotoxity in rats. Intraperitoneal injection of male Wistar rats with CCl 4 1 mL kg 21 , 1:1 mixture with corn oil for 3 days increased serum alanine transaminase, aspartate transaminase, and alkaline phosphatase activities as well as total bilirubin, triglycerides and total cholesterol levels. This is in addition to the disrupted histolog- ical architecture in the CCl 4 group. Rats receiving CCl 4 and co-treated with TLM (3 and 10 mg kg 21 , orally) showed ameliorated serum biochemical and histological changes almost to the control level. Neverthe- less, rats treated with TLM (1 mg kg 21 ) didn’t show any significant changes compared to CCl 4 intoxicated group. In addition, TLM rectified oxidative status disrupted by CCl 4 intoxication. Interestingly, TLM pro- tected against CCl 4 -induced expressions of nuclear factor-jB, inducible nitric oxide synthase and cyclooxygenase-II, in a dose related manner. Moreover, TLM (3 and 10 mg kg 21 ) significantly modified CCl 4 -induced elevation in tumor necrosis factor-a and nitric oxide levels. Furthermore, TLM showed a marked decline in CD681 cells stained areas and reduced activity of myeloperoxidase enzyme compared to CCl 4 -intoxicated group. In conclusion, both doses of TLM (3 and 10 mg kg 21 ) showed significant hepato-protective effects. However, TLM at a dose of 10 mg kg 21 didn’t show significant efficacy above 3 mg kg 21 which is nearly equivalent to the human anti-hypertensive dose of 40 mg. Thus, may be effec- tive in guarding against several hepatic complications due to its antioxidant and anti-inflammatory activ- ities. V C 2016 Wiley Periodicals, Inc. Environ Toxicol 00: 000–000, 2016. Keywords: : telmisartan; carbon tetrachloride; inflammation; oxidative stress; hepatotoxicity INTRODUCTION Many etiological factors induce liver injury, including infec- tious agents, drugs, and hepatotoxic chemicals. Carbon tetra- chloride (CCl 4 ) is a common industrial solvent and a potent hepatotoxin used for inducing liver injury in experimental animal studies (Karakus et al., 2011). CCl 4 induces liver injuries probably through the formation of reactive inter- mediates such as the trichloromethyl radical (CCl : 3 ) which reacts with molecular oxygen to form the trichloromethyl- peroxy radical (CCl 3 OO . ). These free radicals are thought to react with membrane lipids, resulting in their peroxidation and thus liver injury (Packer et al., 1978; Basu, 2003). Besides oxidative stress, inflammation has been shown to be mainly implicated in acute hepatotoxicity which is ascribed to inflammatory cells activation rather than the damaging agent itself (Reyes-Gordillo et al., 2007). Nuclear factor (NF)-jB plays a cardinal role in regulating inflammatory response via activating the expression of genes encoding pro-inflammatory enzymes such as cyclooxygenase-II (COX-II) and inducible nitric oxide synthase (iNOS) as well Correspondence to: Prof. E. El-Demerdash; e-mail: ebtehal_dm@ yahoo.com or ebtehal_dm@pharma.asu.edu.eg Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/tox.22240 V C 2016 Wiley Periodicals, Inc. 1