Hepatoprotective effect of infliximab, an anti-TNF-alpha agent, on carbon tetrachloride-induced hepatic fibrosis

Inflammation. 2008 Aug;31(4):215-21. doi: 10.1007/s10753-008-9067-1. Epub 2008 Apr 22.

Abstract

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.

MeSH terms

  • Actins / metabolism
  • Alanine Transaminase / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antibodies, Monoclonal / pharmacology*
  • Aspartate Aminotransferases / metabolism
  • Carbon Tetrachloride / toxicity*
  • Infliximab
  • Liver Cirrhosis / chemically induced*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / prevention & control*
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Actins
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Carbon Tetrachloride
  • Aspartate Aminotransferases
  • Alanine Transaminase