Protective effects of gallic acid and SGK1 inhibitor on oxidative stress and cardiac damage in an isolated heart model of ischemia/reperfusion injury in rats

by Selleckchem | May 29 2023

Objectives: Oxidative stress and serum and glucocorticoid-induced Kinase 1 gene (SGK1) 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 GSK650394 (as SGK1 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 6 groups with or without pretreatment with gallic acid for 10 days. After that, the heart was isolated and perfused with Krebs-Henseleit solution. A 30 min of ischemia was performed followed by a 60 min reperfusion. In 2 groups, GSK650394 was infused 5 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 SGK1 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 SGK1 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.

Comments：

In this study, the researchers investigated the effects of coadministration of gallic acid and the SGK1 gene inhibitor GSK650394 on cardiac ischemia/reperfusion (I/R) injury in a rat model. The study involved dividing 60 male Wistar rats into 6 groups, with or without pretreatment with gallic acid for 10 days. The heart was isolated and perfused with Krebs-Henseleit solution, followed by a 30-minute ischemia and a 60-minute reperfusion. Two groups were also infused with GSK650394 5 minutes before ischemia induction.

The results of the study indicated that the combined therapy significantly improved the activity of endogenous antioxidant enzymes and total antioxidant capacity compared to each drug alone. Moreover, the coadministration of both drugs significantly reduced the levels of cardiac marker enzymes (CK-MB, LDH, and cTn-I), MDA, ROS, infarct size, and SGK1 gene expression compared with the ischemic group.

Therefore, the study suggests that the combination of gallic acid and GSK650394 may have a more beneficial effect on cardiac I/R injury than either drug alone. This finding could be significant for the development of future therapeutic strategies for the treatment of cardiac ischemia/reperfusion injury.