Ischemic preconditioning decreased leukotriene C4 formation by depressing leukotriene C4 synthase expression and activity during hepatic I/R injury in rats.

Fenfang Hong, Shulong Yang

Department of Physiology, College of Medicine, Nanchang University, Nanchang, China.

The Journal of surgical research 2012 Dec

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Extensive experimental and clinical studies have shown that ischemic preconditioning (IP) can produce protective effects during hepatic ischemia reperfusion (I/R) injury. Our recent studies indicate that rat liver I/R injury is related to an abnormal increase in leukotriene (LT) C4 production. However, the mechanisms underlying IP actions on LTC4 generation during hepatic I/R injury remain to be explored. We randomly divided adult male Sprague-Dawley rats into sham (control), I/R, and IP groups (n = 6). We subjected rat liver to 60 min partial hepatic ischemia followed by 5 h reperfusion with saline administered intravenously. We detected protein expression of LTC4 synthase (LTC4S) with Western blot, and measured LTC4 synthesis enzymes' activities and content by reverse-phase high-performance liquid chromatography. We assessed tissue injury using serum aspartate aminotransferase and aspartate aminotransferase activities and histologic changes. We examined liver tissue glutathione levels by a biochemical method. Ischemic preconditioning markedly decreased LTC4 content, reduced LTC4S protein expressions, and inhibited LTC4 synthesis enzymes' activities in rat liver compared with the I/R group (P < 0.05). We also observed a decline in serum alanine aminotransferase and aspartate aminotransferase activities (P < 0.05), together with hepatic tissue glutathione elevation (P < 0.05) in the IP groups. Positive expression of LTC4S on hepatocytes and sinusoidal endothelial cells in the IP group was significantly lower than that in the I/R group. These findings demonstrate that reduced LTC4 production by IP treatment during hepatic I/R injury could partially result from the down-regulation of LTC4S protein expression and the depression of LTC4 synthesis enzyme activity. They suggest that the beneficial effects of IP may be involved in repression of LTC4 generation during hepatic I/R injury. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

Fenfang Hong, Shulong Yang. Ischemic preconditioning decreased leukotriene C4 formation by depressing leukotriene C4 synthase expression and activity during hepatic I/R injury in rats. The Journal of surgical research. 2012 Dec;178(2):1015-21