Chronic quercetin supplementation modulates cardiac function and signaling pathways in aged male Wistar rat hearts subjected to ischemia-reperfusion.

OBJECTIVES

Quercetin (QCT), a natural polyphenol with antioxidant, anti-inflammatory, and antithrombotic properties, has shown cardioprotective effects in various in vitro and in vivo models of myocardial ischemia/reperfusion (I/R) injury. However, these effects have predominantly been demonstrated in young, healthy animals, which limit their translational potential, as patients with ischemic heart disease are typically middle-aged or older and frequently present with comorbidities. The present study aimed to evaluate the cardioprotective potential of chronic QCT treatment in aged rats.

METHODS

Male Wistar rats (20 months old at arrival) received QCT orally (20 mg/kg/day) for 6 weeks. After treatment, rats were euthanized and isolated hearts were perfused according to Langendorff, subjected to 30 min of global ischemia and 120 min of reperfusion. Cardiac function recovery was monitored during the first 40 min of reperfusion by assessment of electrical and mechanical parameters. Infarct size was determined by TTC staining at the end of reperfusion. In parallel groups, left ventricular tissue was collected immediately after treatment for Western blot (WB) analysis of regulatory proteins.

RESULTS

QCT administration improved electrical function, mainly by reducing QT and QTc intervals during reperfusion compared with controls. In contrast, QCT did not improve recovery of contractile function, and it did not reduce infarct size. WB analysis revealed a significantly increased Bcl-2/Bax ratio, suggesting attenuated apoptosis, while expression of other apoptotic and autophagy-related proteins remained unaffected.

CONCLUSIONS

Compared with juvenile rat hearts, chronic QCT treatment exerts modest cardioprotective effects in aged hearts, characterized by improved electrical recovery and reduced pro-apoptotic signaling, independent of Reperfusion Injury Salvage Kinase (RISK) pathway or autophagy activation.