SP600125, a selective JNK inhibitor, aggravates hepatic ischemia-reperfusion injury.
c-Jun N-terminal kinase (JNK) is activated during hepatic reperfusion, and JNK inhibitors are known to protect other major organs from ischemia-reperfusion (I/R) injury. We attempted to determine the effect of SP600125, a JNK inhibitor, on hepatic I/R injury using a partial ischemia model in mice. Compared to a vehicle-treated group, the SP600125- treated group showed a greater increase in serum ALT levels 24 h after reperfusion with more severe parenchymal destruction and leukocyte infiltration. Similarly, tissue myeloperoxidase and malondialdehyde levels were higher in the SP600125-treated group, and chemokine expression was also higher in the SP600125-treated group. These data, which are contradictory to previous results, indicate that JNK inhibition by SP600125 may be harmful in hepatic I/R injury. Therefore, care must be taken when investigating the therapeutic use of JNK inhibitors in hepatic I/R injury, especially in the context of the effects of JNK inhibition on inflammatory infiltration.
Lee
Kyung-Hoon
KH
Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
Kim
Sang-Eun
SE
Lee
Yun-Song
YS
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D018925:Chemokines / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000293:injuries*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy*
D000873:Anthracenes; D018925:Chemokines; C432165:pyrazolanthrone; D048670:MAP Kinase Kinase 4; D020780:Matrix Metalloproteinase 9