Effect of Sodium Thiosulfate on Isolated Cardiac Interfibrillar and Subsarcolemmal Mitochondria

Abstract

Shakila Banu, et al.: Effect of Sodium Thiosulfate on Isolated Cardiac MitochondriaMitochondria are the key players of cardiac function and their dysfunction due to oxidative stress is implicated in myocardial ischemia reperfusion injury, one of the important mediators of cardiac mortality. The present study evaluates the mitochondrial protective effect of sodium thiosulfate on isolated cardiac mitochondria (interfibrillar mitochondria and subsarcolemmal mitochondria) subjected to oxidative stress by ischemia and reperfusion. Briefly, interfibrillar mitochondria and subsarcolemmal mitochondria were treated with cobalt chloride (500 µM) for 20 min to induce oxidative stress by chemical method and nitrogen gas purging for 20 min in an ischemic buffer was used for the physiological method. The mitoprotective effect of sodium thiosulfate was evaluated with different mode of sodium thiosulfate incubation (pretreatment, cotreatment and post treatment) with the mitochondria. The mitochondria led to an increased oxidative stress (measured by malondialdehyde, reduced glutathione, superoxide dismutase and glutathione peroxidase) and decreased mitochondrial enzyme activities (measured by succinate dehydrogenase, malate dehydrogenase and NAD+ dehydrogenase) with both the models and sodium thiosulfate treated groups showed significant improvement in the above alterations. By comparing the efficiency among the different modes of sodium thiosulfate treatment, we found that pretreatment renders significant (P<0.05) mitochondrial protection against ischemia reperfusion injury by nitrogen gas. However, no such differences were observed among the treatments in cobalt chloride mediated mitochondrial dysfunction. In summary, we found that sodium thiosulfate can modulate and preserve cardiac mitochondria for the treatment of myocardial ischemia reperfusion injury.Key words: Interfibrillar mitochondria (IFM), subsarcolemmal mitochondria (SSM), oxidative stress, sodium thiosulfate, mitochondrial dysfunctionMitochondrial dysfunction leads to a wide range of cardiac pathologies including myocardial ischemia reperfusion, because of its primary role in heart metabolism with respect to energy production, metabolism and homeostasis. Incidentally, the majority of intracellular reactive oxygen species (ROS, superoxide, hydroxide and hydrogen peroxide) that mediate the oxidative stress, are derived from mitochondria via electron transport chain (ETC), especially complex I and complex III redox sites [1][2][3] . Ischemia reperfusion (I/R) injury, a major contributor to the damage encountered during myocardial infarction is experimentally studied by performing microsurgery on rodents; isolated heart perfusion with Langendorff setup and by mimicking it in cell lines utilizing anaerobic chamber. All these approaches have their own benefits with certain limitations and thus the translation of the preclinical results from these models is not very encouraging. Considering the significant role of mitochondria in determining the pathology of I/R injury ...