SP600125, a selective JNK inhibitor, aggravates hepatic ischemia-reperfusion injury.
- Author:
Kyung Hoon LEE
1
;
Sang Eun KIM
;
Yun Song LEE
Author Information
1. Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea. yslee@skku.edu
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- Keywords:
anthra(1,9-cd)pyrazol-6(2H)-one;
ischemia;
JNK mitogen-activated protein kinases;
liver;
reperfusion injury
- MeSH:
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
- From:Experimental & Molecular Medicine
2006;38(4):408-416
- CountryRepublic of Korea
- Language:English
-
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.
