Inhibitory Effect Of Zileuton On Inflammatory Injury To Myocardium Following Ischemia/Reperfusion In Rats

ObjectiveTo investigate the protective effect of zileuton, an inhibitor of5-lipoxygenase (5-LO), on ischemia/reperfusion (I/R) injury of ratmyocardium, and its probable mechanisms.MethodsThirty female SD rats were randomly divided into3groups (10each):sham group (S group), ischemic/reperfusion group (I/R group), andzileuton group (Z group). The I/R model was reproduced by left anteriordescending (LAD) artery occlusion for45min followed by120-minreperfusion. To rats of Z group3mg/kg zileuton was given15min beforeischemia. Animals were sacrificed after reperfusion. The degree ofmyocardial damage was determined by means of pathological examination.Myocardial apoptosis was identified by TUNEL assay. The levels ofleukotriene B4(LTB4), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in plasma were determined by ELISA; the distribution of5-LO in neutrophils was determined by immunofluorescence and Westernblotting. ResultsCompared with I/R group, zileuton attenuated the I/R-inducedmyocardial damage significantly. TUNEL assay demonstrated a significantdecrease in myocardial apoptosis by zileuton (P<0.05). Inflammatorycytokines, including LTB4, IL-1β and TNF-α in the plasma weresignificantly decreased in Z group than in I/R group (P<0.05). Additionally,immunofluorescence and Western blotting showed that zileutonsignificantly inhibited the activation and redistribution of5-LO (P<0.05).However, no significant difference in total5-LO protein expression wasfound among the three groups (P>0.05).ConclusionZileuton may protect myocardium from I/R injury in rats throughsuppressing myocardial apoptosis and inflammation by inhibiting the5-LOactivation and redistribution.