Exp Mol Med.  2006 Aug;38(4):408-416.

SP600125, a selective JNK inhibitor, aggravates hepatic ischemia-reperfusion injury

• Lee KH
• Kim SE
• Lee YS

Abstract

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.

Keyword

anthra(1,9-cd)pyrazol-6(2H)-one; ischemia; JNK mitogen-activated protein kinases; liver; reperfusion injury

MeSH Terms

Reperfusion Injury/*drug therapy
Oxidative Stress/drug effects
Mice, Inbred C57BL
Mice
Matrix Metalloproteinase 9/metabolism
Male
MAP Kinase Kinase 4/*antagonists & inhibitors
Liver/cytology/*drug effects/*injuries
Chemokines/metabolism
Anthracenes/*pharmacology
Animals