Effect of olprinone, a phosphodiesterase III inhibitor, on hepatic ischemia-reperfusion injury in rats.
I/R injury is the main cause for hepatic dysfunction and failure after liver transplantation and liver resection. Therefore, reduction of I/R injury is the most important goal to improve the outcome of these procedures. Olprinone is a newly developed selective phosphodiesterase III inhibitor, which has been reported to ameliorate renal I/R injury in rats. However, no clear evidence for the actions of olprinone on inflammatory response after hepatic I/R injury has been disclosed thus far. Our study was designed to evaluate the action of olprinone on the hepatic I/R injury in rats. Olprinone increased the cyclic adenosine monophosphate level in injured liver tissue and ameliorated the liver injury after hepatic I/R. Moreover, olprinone suppressed the activation of p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and nuclear factor-kappaB, cytokine production (TNF-alpha, IL-6, and cytokine-induced neutrophil chemoattractant factor 1), and intercellular adhesion molecule 1 expression in liver after hepatic I/R. These observations suggest that olprinone protects liver against I/R injury via the elevation of cyclic adenosine monophosphate level and suppression of intercellular adhesion molecule 1 expression and cytokine production (TNF-alpha, IL-6, and cytokine-induced neutrophil chemoattractant factor 1), possibly by interfering with the signaling pathways of p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and nuclear factor-kappaB in rats.
Yamaguchi
Keisuke
K
Department of Anesthesiology and Pain Medicine, Juntendo University School of Medicine, Tokyo, Japan. keisuke@juntendo.ac.jp
Kawahara
Toshiyasu
T
Kumakura
Seiichiro
S
Hua
Jian
J
Kugimiya
Toyoki
T
Nagaoka
Isao
I
Inada
Eiichi
E
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D007093:Imidazoles / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D011728:Pyridones / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000517:prevention & control*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007093:Imidazoles; D011728:Pyridones; D018799:Intercellular Adhesion Molecule-1; C059498:olprinone; D000242:Cyclic AMP; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases