Inhibition of TNF-α protects against hepatic ischemia-reperfusion injury in rats via NF-κB dependent pathway

Naunyn Schmiedebergs Arch Pharmacol. 2012 May;385(5):465-71. doi: 10.1007/s00210-012-0729-z. Epub 2012 Feb 8.

Abstract

Hepatic ischemia-reperfusion injury (I/R) is a serious health problem associated with liver transplantation, resection surgery, and various types of shock especially hemorrhagic shock. In the present investigation, the effect of inhibition of tumor necrosis factor-alpha (TNF-α) using pentoxifylline or infliximab against hepatic I/R injury induced in rats by 45-min ischemia and 1-h reperfusion was studied. It was observed that both pentoxifylline and infliximab-treated groups showed a significantly lower extent and severity of liver injury. This is attributed to (1) a decrease in oxidative stress markers, (2) reduction of the expression of TNF-α, TNF-α type-1 receptors, and nuclear factor kappa B (NF-κB). Thus TNF-α inhibition may be one of the therapeutic interventions to overcome the deleterious effects of I/R on liver via reduction of oxidative stress and inhibition of inflammatory cascade.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Gene Expression / drug effects
  • Glutathione / metabolism
  • Infliximab
  • L-Lactate Dehydrogenase / blood
  • Liver / drug effects
  • Liver / injuries
  • Liver / metabolism
  • Male
  • Malondialdehyde / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Pentoxifylline / pharmacology
  • Pentoxifylline / therapeutic use*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antibodies, Monoclonal
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Infliximab
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione
  • Pentoxifylline