title: The role of infliximab on paracetamol-induced hepatotoxicity in rats.
abstract: Paracetamol has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Infliximab is tumor necrosis factor alpha (TNF-α) inhibitor agent, which has been developed as a therapeutic agent for TNF-α-mediated disease. It acts by binding and neutralizing TNF. The aim of our study was to evaluate the hepatoprotective activity of infliximab on paracetamol-induced hepatotoxicity and to understand the relationship between the TNF-α and paracetamol-induced liver injury. Fifty-six rats were divided into eight groups as each composed of seven rats: (1) intact, (2) 7 mg/kg infliximab, (3) 140 mg/kg NAC, (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 3 mg/kg infliximab, (7) 2 g/kg paracetamol + 5 mg/kg infliximab and (8) 2 g/kg paracetamol + 7 mg/kg infliximab groups. Liver function tests including lipid peroxidation levels were analyzed and histopathological changes of liver were also observed. There were statistically significant increases in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), levels of TNF-α and malondialdehyde (MDA) and decreases in the activity of superoxide dismutase (SOD) and level of glutathione (GSH) in the group treated with paracetamol. Infliximab administration dramatically reduced serum ALT, AST and TNF-α level. Also, it restored GSH, SOD and decreased MDA levels in liver. Liver histopathological examination showed that infliximab administration antagonized paracetamol-induced liver pathological damage. The results of present study suggest that infliximab has significant hepatoprotective activity on paracetamol-induced hepatotoxicity.
authors.affiliation: Department of Pharmacology, Ataturk University Faculty of Medicine, Erzurum, Turkey.
authors.forename: Irmak
authors.initials: I
authors.lastname: Ferah
authors.forename: Zekai
authors.initials: Z
authors.lastname: Halici
authors.forename: Yasin
authors.initials: Y
authors.lastname: Bayir
authors.forename: Elif
authors.initials: E
authors.lastname: Demirci
authors.forename: Bunyami
authors.initials: B
authors.lastname: Unal
authors.forename: Elif
authors.initials: E
authors.lastname: Cadirci
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D007150:Immunohistochemistry; D000069285:Infliximab; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000975:Antioxidants; D016207:Cytokines; D008054:Lipid Peroxides; D014409:Tumor Necrosis Factor-alpha; D000082:Acetaminophen; D008315:Malondialdehyde; D000069285:Infliximab