Quercetin attenuates ferroptosis-associated myocardial injury in rats after coronary microembolization by activating the Nrf2/HO-1 signaling pathway.

OBJECTIVES: Coronary microembolization (CME) significantly contributes to the progression of heart failure and is strongly associated with adverse clinical outcomes in patients. Ferroptosis has been implicated in CME-induced myocardial injury. Quercetin has well-documented anti-inflammatory and antioxidant properties and shows therapeutic potential in coronary artery disease. However, its precise mechanism for regulating ferroptosis during CME-mediated myocardial injury remains unclear. This study aims to elucidate the therapeutic effects of quercetin and its underlying molecular mechanisms that regulate ferroptosis in cardiomyocytes following CME. MATERIALS AND METHODS: The Sprague-Dawley(SD) rats were randomly divided into four groups (n=7 each): Sham, CME, CME+Quercetin (Que), and CME+Quercetin+ML385 (Que+ML385). The CME model was produced by injecting microspheres into the left ventricles. We administered pharmacological treatments as follows: The Que and Que+ML385 groups received daily oral quercetin (250 mg/kg) starting 7 days before model induction until the procedure day. Additionally, we pretreated the Que+ML385 group with intraperitoneal injection of ML385 (30 mg/kg) 2 hr before CME induction. The comprehensive evaluations include cardiac function assessment, quantification of serum biomarkers of myocardial injury, cardiac tissue histology, and analysis of ferroptosis-related molecular markers to evaluate quercetin's therapeutic effects. RESULTS: Quercetin pretreatment significantly improved cardiac function, reduced serum markers of myocardial injury, and decreased microinfarction size. At the molecular level, quercetin up-regulated Nrf2 and HO-1 expression and attenuated biochemical markers of cardiomyocyte ferroptosis. However, ML385 co-treatment attenuated this protective effect. CONCLUSION: Quercetin may inhibit ferroptosis in cardiomyocytes by activating the Nrf2/HO-1 signaling pathway, thereby improving CME-related cardiac dysfunction and reducing myocardial injury.