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


CONCLUSIONS
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.
Kaibori
M
M
Department of Surgery, Kansai Medical University, Osaka, Japan. kaibori@takii.kmu.ac.jp
Yanagida
H
H
Uchida
Y
Y
Yokoigawa
N
N
Kwon
A-H
AH
Okumura
T
T
Kamiyama
Y
Y
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D004731:Endotoxins / Q000633:toxicity; D007511:Ischemia / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011728:Pyridones / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004731:Endotoxins; D011728:Pyridones; C093844:pirfenidone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase