Original CommunicationsP38 mitogen-activated protein kinase inhibition attenuates ischemia-reperfusion injury of the rat liver*,**
Section snippets
Animals
Adult male Sprague-Dawley rats weighing 280 to 340 g were used in this experiment. Animals were allowed free access to food and water in a constant temperature environment with a 14-hour to 10-hour light-dark cycle. All animals were maintained in accordance with the guidelines described in the “Guide for the Care and Use of Laboratory Animals” (National Institutes of Health publication 85-23, revised 1985). This study was performed with the approval of the Animal Care and Experimentation
Results
After 2 hours of reperfusion, serum levels of AST, ALT, LDH, and TNF-α in the FR-treated group were significantly lower than those in the control group. Serum levels of IL-1β in the FR-treated group were lower than those in the control group; however, there was no significant difference. Serum levels of TNF-α and IL-1β in the FR-treated group were not significantly different from those in the sham-operated and FR-only groups. Serum levels of AST, ALT, and LDH in the FR-only group were not
Discussion
TNF-α and IL-β derived from activated Kupffer's cells play an important role in the pathogenesis of hepatic ischemia-reperfusion injury. These cytokines are capable of up-regulating adhesion molecules and cause polymorphonuclear neutrophils to adhere to endothelial cells. This causes microcirculation disturbance, which is thought to be a major mechanism of ischemia-reperfusion injury, including the “no-flow phenomenon.”23
MAPK family members are activated by dual phosphorylation on tyrosine and
Conclusion
In this warm ischemic model, both p38 MAPK and JNK were phosphorylated during the reperfusion process after ischemia. FR decreased serum TNF-α and IL-1β levels, liver injury associated with the inhibition of p38 MAPK activation, and the noninhibited phosphorylation of JNK. These results suggest that inhibiting the activation of p38 MAPK may attenuate warm ischemia-reperfusion injury of the liver.
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This work was supported in part by a fund from Fujisawa Pharmaceutical Co Ltd, Osaka, Japan.
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Reprint requests: Izumi Takeyoshi, Second Department of Surgery, Gunma University School of Medicine, 3-39-15, Showa Machi, Maebashi, Gunma 371-8511, Japan.