Exploring the Cardioprotective Effects of Pharmacological Inhibitors of PFKFB3 in Ischemia-Reperfusion-Subjected Rats

Background and Objective: PFKFB3 (6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase-3) is an enzyme that regulates glycolysis and is activated under hypoxic conditions. However, the role of this enzyme and its pharmacological inhibitors in ischemia-reperfusion injury is not explored yet. The present study was aimed to explore the effects of two pharmacological inhibitors of PFKFB3, 3-PO and AZ PFKFB3 in ischemia-reperfusion-induced myocardial injury along with possible mechanisms. Materials and Methods: Wistar albino rats were subjected to ex vivo ischemia-reperfusion injury on the Langendorff apparatus. The degree of myocardial injury was assessed by measuring the release of cTnT and CK-MB in the coronary effluent.The Left Ventricular Developed Pressure (LVDP) was measured to assess the heart contractility. The hearts were perfused with 3-PO and AZ PFKFB3 before subjecting them to ischemia and reperfusion injury. The hearts were homogenized to measure the levels of H2S, p-Akt and p-GSK-3 beta/GSK-3 beta ratio to explore the mechanism of PFKFB3 inhibitors. Results: Perfusion of hearts with 3-PO and AZ PFKFB3 alleviated ischemia-reperfusion-induced increase in CK-MB, cTnT release and restored the LVDP values suggesting their cardioprotective actions. These drugs restored the levels of H2S and p-Akt in the heartalong with the increase in the p-GSK-3B/GSK-3 beta ratio. Conclusion: Pharmacological inhibitors of PFKFB3 may be potentially employed as cardioprotective agents to attenuate ischemia-reperfusion-induced injury and these effects may be mediated involving H2S, Akt and GSK-3 beta signalling.