The protective effects of gallic acid and SGK1 inhibitor on cardiac damage and genes involved in Ca2+ homeostasis in an isolated heart model of ischemia/reperfusion injury in rat

Serum and glucocorticoid-induced kinase 1 (SGK1) is an Enzyme that may play a vital role in myocardial ischemia/reperfusion (I/R) injury. This Enzyme may affect sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2), ryanodine receptor (RyR2) and sodium/calcium exchanger (NCX1) during myocardial ischemia/reperfusion injury. The objective of this investigation was to analyze the effects of the combination of GSK650394 (SGK1 Inhibitor) and gallic acid on the calcium ions regulation, inflammation, and cardiac dysfunction resulting from ischemia/reperfusion (I/R) injury in the heart. Sixty male Wistar rats were randomly divided into six groups, pretreated with gallic acid or vehicle for 10 days. Then the heart was isolated and exposed to I/R. In the SGK1 Inhibitor groups, GSK650394 was infused 5 min before ischemia induction. After that, Ca²⁺ homeostasis, inflammatory factors, cardiac function, antioxidant activity, and myocardial damage were evaluated. The findings suggested that the use of two drugs in combination therapy produced more significant improvements in left ventricular end diastolic pressure, left ventricular systolic pressure, RR-interval, ST-elevation, inflammation factors, and antioxidant enzymes activity as compared to the use of each drug. Despite this, there was a significant decrease observed in heart marker enzymes (including Lactate Dehydrogenase (LDH), troponin-I (cTn-I), creatine kinase-MB (CK-MB) and creatine phosphokinase (CPK) when compared to the ischemic group. Additionally, the expression of RyR2, NCX1, and SERCA2 genes showed a noteworthy increase as compared to the ischemic group. The findings of this study propose that using both of these agents on myocardial I/R injury could have superior advantages compared to using only one of them.

GSK650394; Gallic acid; Inflammation; Oxidative stress; Reperfusion injury; Serum-glucocorticoid regulated kinase 1 (SGK1).