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

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.

• Authors: Kyung-Hoon Lee, Sang-Eun Kim, Yun-Song Lee
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 38 Issue 4 Pg. 408-16 (Aug 31 2006) ISSN: 1226-3613 [Print] United States
• PMID: 16953120 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracenes
• Chemokines
• pyrazolanthrone
• MAP Kinase Kinase 4
• Matrix Metalloproteinase 9

Topics

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