An antibody of TNF-alpha did not prevent thioacetamide-induced hepatotoxicity in rats.
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.
Department of Gastroenterology, Firat University Medical Faculty, Elazig, Turkey.
Ulvi
U
Demirel
Murat M M
MM
Harputluoglu
Yuksel
Y
Seckin
Harun
H
Ciralik
Ismail
I
Temel
Fatma
F
Ozyalin
Baris
B
Otlu
Bilgic
B
Yilmaz
Mehmet Sarp
MS
Dincturk
Hulya
H
Aladag
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000931:Antidotes / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004336:Drug Antagonism; D000069285:Infliximab; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000931:Antidotes; D014409:Tumor Necrosis Factor-alpha; D013853:Thioacetamide; D000069285:Infliximab