Yogeeta Surinder Kumar, Raghavendran Hanumantha Rao Balaji, Gnanapragasam Arunachalam, Subhashini Rajakannu, Devaki Thiruvengadam
Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India.
Chem Biol Interact. 2006 Oct 27;163(1-2):160-9. doi: 10.1016/j.cbi.2006.04.018.
Disruption of mitochondria and free radical mediated tissue injury have been reported during cardiotoxicity induced by isoproterenol (ISO), a beta-adrenergic catecholamine. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on the mitochondrial damage in ISO induced cardiotoxicity. Induction of rats with ISO (150 mg/kg b.wt., i.p.) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c-oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, GSH), cytochromes (b, c, c1, aa3) and in the level of mitochondrial phospholipids. A marked elevation in mitochondrial lipid peroxidation, mitochondrial levels of cholesterol, triglycerides and free fatty acids were also observed in ISO intoxicated rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt.) and AA (80 mg/kg b.wt.) orally for 6 days significantly enhanced the attenuation of these functional abnormalities and restored normal mitochondrial function when compared to individual drug treated groups. Mitigation of ISO induced biochemical and morphological changes in mitochondria were more pronounced with a combination of FA and AA rather than the individual drug treated groups. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings demonstrate the synergistic ameliorative potential of FA and AA on mitochondrial function during beta-adrenergic catecholamine induced cardiotoxicity and associated oxidative stress in rats.
异丙肾上腺素（ISO）是一种β-肾上腺素能儿茶酚胺，据报道，在其诱导的心脏毒性过程中会出现线粒体破坏和自由基介导的组织损伤。本研究旨在探讨阿魏酸（FA）和抗坏血酸（AA）联合使用对ISO诱导的心脏毒性中线粒体损伤的影响。用ISO（150mg/kg体重，腹腔注射）诱导大鼠2天，导致呼吸链酶（NADH脱氢酶和细胞色素c氧化酶）、三羧酸循环酶（异柠檬酸脱氢酶、琥珀酸脱氢酶、苹果酸脱氢酶、α-酮戊二酸脱氢酶）、线粒体抗氧化剂（谷胱甘肽过氧化物酶、谷胱甘肽S-转移酶、超氧化物歧化酶、过氧化氢酶、谷胱甘肽）、细胞色素（b、c、c1、aa3）的活性以及线粒体磷脂水平显著降低。在ISO中毒的大鼠中还观察到线粒体脂质过氧化、线粒体胆固醇、甘油三酯和游离脂肪酸水平显著升高。与单独用药治疗组相比，预先口服FA（20mg/kg体重）和AA（80mg/kg体重）联合用药6天可显著增强这些功能异常的减轻程度，并恢复正常的线粒体功能。与单独用药治疗组相比，FA和AA联合使用对ISO诱导的线粒体生化和形态学变化的减轻作用更为明显。透射电子显微镜观察结果也与这些生化参数相关。因此，这些发现证明了FA和AA在β-肾上腺素能儿茶酚胺诱导的大鼠心脏毒性及相关氧化应激过程中对线粒体功能具有协同改善作用。
