Pirfenidone protects endotoxin-induced liver injury after hepatic ischemia in rats

Transplant Proc. 2004 Sep;36(7):1973-4. doi: 10.1016/j.transproceed.2004.08.061.

Abstract

Background: Pirfenidone (PFD), an experimental antifibrotic agent, was investigated for its effects on endotoxin-induced liver injury after hepatic ischemia-reperfusion.

Methods: Male Sprague-Dawley rats were subjected to 30 minutes of partial hepatic ischemia, followed by reperfusion for 24 hours. Lipopolysaccharide (LPS) was injected at 30 minutes of reperfusion. PFD (300 mg/kg) or its vehicle (0.5% carboxymethylcellulose) was given orally following LPS administration.

Results: PFD prevented the increase in activities of serum alanine transaminase, aspartate transaminase, and lactate dehydrogenase after reperfusion. PFD inhibited the increase of cytokine-induced neutrophil chemoattractant in serum and liver tissue. The number of neutrophils infiltrating the liver was significantly lower in the PFD-treated group than the control group.

Conclusion: These results indicate that PFD prevents endotoxin-induced liver injury after hepatic ischemia-reperfusion, in part through the decrease of neutrophil infiltration to the liver.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Endotoxins / toxicity
  • Ischemia / prevention & control*
  • Liver / drug effects*
  • Liver / pathology
  • Male
  • Pyridones / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Endotoxins
  • Pyridones
  • pirfenidone
  • Aspartate Aminotransferases
  • Alanine Transaminase