An antibody of TNF-alpha did not prevent thioacetamide-induced hepatotoxicity in rats

• Published in: Human & experimental toxicology 2011-07, Vol.30 (7), p.560-566
• Main Authors: Demirel, Ulvi, Harputluoglu, Murat MM, Seckin, Yuksel, Ciralik, Harun, Temel, Ismail, Ozyalin, Fatma, Otlu, Baris, Yilmaz, Bilgic, Dincturk, Mehmet Sarp, Aladag, Hulya
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Antidotes - pharmacology; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; Drug Antagonism; Infliximab; Lipid Peroxidation - drug effects; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver Function Tests; Male; Oxidative stress; Oxidative Stress - drug effects; Rats; Rats, Wistar; Rodents; Thioacetamide - toxicity; TNF inhibitors; Toxicity; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327110374206

Tumor necrosis factor (TNF)-α antibodies have been shown to reduce liver damage in different models. We investigated the effects of infliximab (a TNF-α antibody) on liver damage in thioacetamide (TAA)-induced hepatotoxicity in rats. Group 1 (n = 8) was the control group. In group 2 (n = 8), the TAA group, the rats received 300 mg/kg intraperitoneal (ip) TAA daily for 2 days. In group 3 (n = 8), the TAA + Infliximab (INF) group, infliximab (5 mg/kg ip daily) was administered 48 hours before the first dose of TAA daily for 2 days and was maintained for 4 consecutive days. In group 4 (n = 8), the INF group, the rats received only ip infliximab (5 mg/kg) daily. Livers were excised for histopathological and biochemical tests (thiobarbituric-acid-reactive substances [TBARS], and myeloperoxidase [MPO]). Serum ammonia, aspartate transaminase (AST), alanine transaminase (ALT), TNF-α, liver TBARS and MPO levels, and liver necrosis and inflammation scores in the TAA group were significantly higher than in the control and INF groups (all p < 0.01). All parameters except AST were not significantly different between TAA and TAA + INF. In conclusion, our results suggest that oxidative stress plays an important role in TAA-induced hepatotoxicity, and infliximab does not improve oxidative liver damage.