Protective effects of gallic acid and SGK۱ inhibitor on oxidative stress and cardiac damage in an isolated heart model of ischemia/reperfusion injury in rats

Objective(s): Oxidative stress and serum and glucocorticoid-induced Kinase ۱ gene (SGK۱) perform a central role in the consequences of ischemia in the heart. This research aimed to investigate the effect of coadministration of gallic acid and the GSK۶۵۰۳۹۴ (as SGK۱ gene inhibitor) on the ischemic complications of a rat model of cardiac ischemia/reperfusion (I/R) injury. Materials and Methods: Sixty male Wistar rats were divided into ۶ groups with or without pretreatment with gallic acid for ۱۰ days. After that, the heart was isolated and perfused with Krebs-Henseleit solution. A ۳۰ min of ischemia was performed followed by a ۶۰ min reperfusion.  In ۲ groups, GSK۶۵۰۳۹۴ was infused ۵ min before ischemia induction. Ten minutes after reperfusion commencement, cardiac marker enzyme (CK-MB, LDH, and cTn-I) activities were measured in the cardiac perfusate. At the end of reperfusion, the activity of anti-oxidant enzymes (Catalase, Superoxide dismutase, and Glutathione peroxidase), lipid peroxidation (MDA), total anti-oxidant capacity (TAC), intracellular reactive oxygen species (ROS), infarct size, and SGK۱ gene expression were measured in the heart tissue. Results: The results indicated that dual therapy with both drugs significantly improved endogenous anti-oxidant enzyme activity and TAC more than each drug alone. However, the heart marker enzymes (CK-MB, LDH, and cTn-I), MDA, ROS, infarct size, and SGK۱ gene expression were reduced significantly compared with the ischemic group. Conclusion: The results of this study suggest that concomitant administration of both drugs in the case of cardiac I/R injury may have a more beneficial effect than each one alone.