Sulfaphenazole Attenuates Myocardial Cell Apoptosis Accompanied With Cardiac Ischemia–Reperfusion by Suppressing the Expression of BimEL and Noxa

Journal of Pharmacological Sciences

Yasuhiro Ishihara¹  Norio Shimamoto² 

[1] Graduate School of Integrated Arts and Sciences, Hiroshima University, Japan;Laboratory of Pharmacology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Japan

关键词: heart;    ischemia–reperfusion injury;    apoptosis;    mitochondria;    sulfaphenazole;   

DOI  :  10.1254/jphs.12079FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(33)Cited-By(3)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.

【 授权许可】

Unknown