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Inhibitory effect of zileuton on inflammatory injury to myocardium following ischemia/reperfusion in rats

By Hua-di QIN, Chun-chang QIN, Hai-tao ZHANG, Xue-jing YU and Jing CHANG


Objective  To investigate the protective effect of zileuton, an inhibitor of 5-lipoxygenase (5-LO), on ischemia/ reperfusion (I/R) injury of rat myocardium, and its probable mechanisms. Methods  Thirty female SD rats were randomly divided into 3 groups (10 each): sham group (S group), ischemic/reperfusion group (I/R group), and zileuton group (Z group). The I/ R model was reproduced by left anterior descending (LAD) artery occlusion for 45min followed by 120-min reperfusion. To rats of Z group 3mg/kg zileuton was given 15min before ischemia. Animals were sacrificed after reperfusion. The degree of myocardial damage was determined by means of pathological examination. Myocardial apoptosis was identified by TUNEL assay. The levels of leukotriene B4 (LTB4), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in plasma were determined by ELISA; the distribution of 5-LO in neutrophils was determined by immunofluorescence and Western blotting. Results  Compared with I/ R group, zileuton attenuated the I/R-induced myocardial damage significantly. TUNEL assay demonstrated a significant decrease in myocardial apoptosis by zileuton (P<0.05). Inflammatory cytokines, including LTB4, IL-1β and TNF-α in the plasma were significantly decreased in Z group than in I/R group (P<0.05). Additionally, immunofluorescence and Western blotting showed that zileuton significantly inhibited the activation and redistribution of 5-LO (P<0.05). However, no significant difference in total 5-LO protein expression was found among the three groups (P>0.05). Conclusion  Zileuton may protect myocardium from I/R injury in rats through suppressing myocardial apoptosis and inflammation by inhibiting the 5-LO activation and redistribution. DOI: 10.11855/j.issn.0577-7402.2014.03.0

Topics: zileuton, arachidonate 5-lipoxygenase, myocardial reperfusion injury, Medicine, R, Medicine (General), R5-920
Publisher: Editorial Board of Medical Journal of Chinese People's Liberation Army
Year: 2014
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