Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE.
Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE.
Mol Cell Biochem. 2019 Mar;453(1-2):89-102. doi: 10.1007/s11010-018-3434-5. Epub 2018 Aug 29.
Mitochondrial dysfunction plays crucial role in the pathologenesis of myocardial infarction (MI). The present study evaluated the protective effect of α-bisabolol against isoproterenol (ISO)-induced mitochondrial dysfunction and apoptosis in rats. Male albino Wistar rats were pre- and co-treated with intraperitoneal injection of α-bisabolol (25 mg/kg body weight) daily for 10 days. To induce experimental MI, ISO (85 mg/kg body weight) was injected subcutaneously to the rats at an interval of 24 h for 2 days (9th and 10th day). ISO-induced MI was indicated by the decreased activities of heart creatine kinase and lactate dehydrogenase in rats. ISO administration also enhanced the concentrations of heart mitochondrial lipid peroxidation products and decreased the activities/concentrations of mitochondrial antioxidants, Kreb's cycle dehydrogenases and mitochondrial electron transport chain complexes I, II + III and IV in rats. Furthermore, ISO triggers calcium overload and ATP depletion in the rat's heart mitochondria followed by the mitochondrial cytochrome-C release and the activation of intrinsic pathway of apoptosis by upregulating the myocardial pro-apoptotic Bax, P, APAF-1, active caspase-3, active caspase-9 and down regulating the expressions of anti-apoptotic Bcl-2. α-Bisabolol pre and co-treatment showed considerable protective effects on all the biochemical and molecular parameters studied. Transmission electron microscopic study and mitochondrial swelling assay confirmed our biochemical and molecular findings. The in vitro study on hydroxyl radical also revealed the potent free radical scavenging activity of α-bisabolol. Thus, α-bisabolol attenuates mitochondrial dysfunction and intrinsic pathway of apoptosis in ISO-induced myocardial infarcted rats.
线粒体功能障碍在心肌梗死 (MI) 的发病机制中起着关键作用。本研究评估了 α- 姜黄醇对异丙肾上腺素 (ISO) 诱导的大鼠线粒体功能障碍和细胞凋亡的保护作用。雄性白化 Wistar 大鼠每天经腹腔注射 α- 姜黄醇（25mg/kg 体重）预处理和共同处理 10 天。为了诱导实验性 MI，ISO（85mg/kg 体重）以 24 小时的间隔皮下注射到大鼠中，共 2 天（第 9 天和第 10 天）。ISO 诱导的 MI 通过大鼠心脏肌酸激酶和乳酸脱氢酶活性的降低来指示。ISO 给药还增强了心脏线粒体脂质过氧化产物的浓度，并降低了线粒体抗氧化剂、Kreb 循环脱氢酶和线粒体电子传递链复合物 I、II+III 和 IV 的活性/浓度。此外，ISO 引发大鼠心脏线粒体中的钙超载和 ATP 耗竭，随后通过上调心肌促凋亡 Bax、P、APAF-1、活性 caspase-3、活性 caspase-9 和下调抗凋亡 Bcl-2 的表达，激活细胞凋亡的内在途径。α- 姜黄醇预处理和共同处理对所有研究的生化和分子参数均显示出相当大的保护作用。透射电子显微镜研究和线粒体肿胀测定证实了我们的生化和分子发现。羟基自由基的体外研究也揭示了 α- 姜黄醇的强大自由基清除活性。因此，α- 姜黄醇可减轻 ISO 诱导的心肌梗死大鼠的线粒体功能障碍和内在途径的细胞凋亡。
