Exploring the Cardioprotective Effects of Pharmacological Inhibitors of 6-Phosphofructo-2-kinase/Fructose-2,6- Bisphosphatase-3 in Ischemia-Reperfusion-Subjected Rats

Jingjing Han and Ying Zhang

Background and Objective: Studies have shown the important role of PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3) in endotoxemia-induced myocardial injury and Ischemia-Reperfusion (IR)-induced cerebral injury. However, the role of this enzyme and its pharmacological inhibitors in IR-induced myocardial injury is not yet explored. The present study explored the effects of PFKFB3 inhibitors, 3-PO and AZ PFKFB3 in IR-induced myocardial injury along with possible mechanisms. Material and Methods: In this study, Wistar albino rats were employed. The hearts were removed and perfused on Langendorff apparatus. Thereafter, 30 min of ischemia and 120 min of reperfusion was given to hearts. The levels of cTnT and CK-MB were measured to note the myocardial injury. The Left Ventricular Developed Pressure (LVDP) was also noted to measure the heart contractility. The hearts were perfused with 3-PO and AZ PFKFB3 before giving IR injury to hearts. At the end, the levels of H₂S,p-Akt and ratio of p-GSK-3β/GSK-3βratio was measured in hearts to explore the mechanism of action of PFKFB3 inhibitors. Results: 3-PO and AZ PFKFB3 alleviated IR-induced increase in CK-MB, cTnT and restored LVDP suggesting their cardioprotective actions. These drugs restored the levels of H₂S and p-Akt in the heart along with increase in p-GSK-3β/GSK-3β ratio. Conclusion: PFKFB3 inhibitors may be potentially employed as cardioprotective agents to attenuate IR injury, which may be mediated involving H₂S, Akt and GSK-3β signalling.

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