Hepatoprotective effect of infliximab, an anti-TNF-alpha agent, on carbon tetrachloride-induced hepatic fibrosis.
To assess the effect of infliximab, an anti-tumor necrosis factor (TNF)-alpha agent, on the carbon tetrachloride (CCl(4))-induced hepatic fibrosis in rats. Rats were randomized into three groups (n=9). The control group received only intraperitoneal (i.p.) olive oil. Hepatic fibrosis was induced by repeated i.p. injections of 1.5 ml/kg CCl(4) (1:3 mixture with olive oil) for 5 weeks in the remaining two groups which were also injected subcutaneous saline or 2 mg/kg infliximab. Infliximab reduced the levels of aspartate aminotransferase and alanine aminotransferase (p<0.05 for both). The scores of hepatic necrosis, inflammation and fibrosis, and expression of alpha-smooth muscle actin were lower in the infliximab-treated group than the CCI(4)-treated group (p<0.01, p<0.001, p<0.01, p<0.001, respectively). However, there was no significant difference in terms of liver tissue and plasma malondialdehyde, and serum TNF-alpha levels, while infliximab relatively reduced the level of transforming growth factor-beta(1) (373.0+/-153.1 vs. 280.8+/-127.1 pg/ml). Treatment with infliximab attenuated the necro-inflammation and fibrogenesis in the CCI(4)-induced hepatic fibrosis, and thus it might be effective as a therapeutic anti-fibrotic agent.
Bahcecioglu
Ibrahim Halil
IH
Department of Gastroenterology, Faculty of Medicine, Firat University, Elazig, Turkey.
Koca
Suleyman Serdar
SS
Poyrazoglu
Orhan Kursat
OK
Yalniz
Mehmet
M
Ozercan
Ibrahim Hanifi
IH
Ustundag
Bilal
B
Sahin
Kazim
K
Dagli
Adile Ferda
AF
Isik
Ahmet
A
D000199:Actins / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D000069285:Infliximab; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000199:Actins; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase