Sulfaphenazole attenuates myocardial cell apoptosis accompanied with cardiac ischemia-reperfusion by suppressing the expression of BimEL and Noxa

We previously reported the administration of a potent cytochrome p450 inhibitor,sulfaphenazole (spz),to suppress oxidative stress and the extension of myocardial infarct size in a rat model of cardiac ischemia-reperfusion (i/r). the aim of this study was to investigate the effects of spz on the myocardial cell apoptosis induced by i/r in rats. i/r injury was evoked by ligation of the left anterior descending coronary artery for 1 h,followed by reperfusion for 3 h. tunel-positive nuclei were detected and nucleosomal dna fragmentation was observed 3 h after reperfusion. the administration of spz largely suppressed the cardiac dna fragmentation induced by i/r. a pan-caspase inhibitor,z-vad-fmk,had no effect on dna fragmentation. caspase-3/7 was not activated 3 h after reperfusion. decreases in the mitochondrial membrane potential and cytochrome c release from the mitochondria to cytosol were detected 3 h after reperfusion. the expression levels of bimel and noxa were elevated 3 h after reperfusion. these phenomena were suppressed by the administration of spz. taken together,treatment with spz could attenuate the myocardial cell apoptosis accompanied with i/r by inhibiting the mitochondrial dysfunction due to decreases in the expression of bimel and noxa. © the japanese pharmacological society.