Effect of Gallic Acid Pretreatment and SGK1 Enzyme Inhibition on Cardiac Function and Inflammation in a Rat Model of Ischemia-Reperfusion Injury

Background: Serum and glucocorticoid-induced kinase 1 (SGK1) is an enzyme that may play an important role in ischemic-reperfusion (I/R) injury and myocardial dysfunction. Although many studies have been conducted on individual Antioxidants, little attention has been paid to the effects of co-administration of an antioxidant with an SGK1 Inhibitor on cardiac function after I/R.

Methods: This study aimed to determine the effects of gallic acid (as an antioxidant) combined with an SGK1 Inhibitor on I/R-induced cardiac dysfunction and inflammation. Sixty male Wistar rats were randomized into 6 groups, pretreated with gallic acid or vehicle for 10 days. Subsequently, the heart was isolated and exposed to I/R. In groups that received the SGK1 Inhibitor, the heart was perfused with the SGK1 Inhibitor GSK650394, 5 min before induction of ischemia. After that, cardiac function, inflammatory factors, and myocardial damage were evaluated.

Results: The combination of these two compounds improved cardiac contractility, heart rate, rate pressure product, left ventricular developed pressure, left ventricular systolic pressure, perfusion pressure, and QRS voltage significantly (P < 0.05). In addition, concomitant therapy of these two agents reduced tumor necrosis factor-alpha and interleukin-6, and the activity of creatine kinase-MB, Lactate Dehydrogenase, and troponin-I (P < 0.05).

Conclusion: The results indicated that administration of gallic acid with the SGK1 Inhibitor may have a potentiating effect on the improvement of cardiac dysfunction and I/R-induced inflammation.

Gallic Acid; Inflammation; Ischemic-Reperfusion Injury; Rat; Serum-glucocorticoid regulated kinase 1 (SGK1).