Quercetin attenuates ferroptosis-associated myocardial injury in rats after coronary microembolization by activating the Nrf۲/HO-۱ signaling pathway

Objective(s): 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=۷ each): Sham, CME, CME+Quercetin (Que), and CME+Quercetin+ML۳۸۵ (Que+ML۳۸۵). The CME model was produced by injecting microspheres into the left ventricles. We administered pharmacological treatments as follows: The Que and Que+ML۳۸۵ groups received daily oral quercetin (۲۵۰ mg/kg) starting ۷ days before model induction until the procedure day. Additionally, we pretreated the Que+ML۳۸۵ group with intraperitoneal injection of ML۳۸۵ (۳۰ mg/kg) ۲ 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 Nrf۲ and HO-۱ expression and attenuated biochemical markers of cardiomyocyte ferroptosis. However, ML۳۸۵ co-treatment attenuated this protective effect.Conclusion: Quercetin may inhibit ferroptosis in cardiomyocytes by activating the Nrf۲/HO-۱ signaling pathway, thereby improving CME-related cardiac dysfunction and reducing myocardial injury.

کلیدواژه ها:

Coronary-microembolization ، Ferroptosis ، Nrf۲/HO-۱ ، Oxidative stress ، Quercetin