Quercetin ameliorated remote myocardial injury induced by renal ischemia/reperfusion in rats: Role of Rho-kinase and hydrogen sulfide

Abstract

Aims: This study was designated to investigate the means through which quercetin confers its cardioprotective action against remote cardiomyopathy elicited by renal ischemia/reperfusion (I/R). Potential involvement of hydrogen sulfide (H₂S) and its related mechanisms were accentuated herein.

Main methods: In anesthetized male Wistar rats, renal I/R was induced by bilateral renal pedicles occlusion for 30 min (ischemia) followed by 24 h reperfusion. Quercetin (50 mg/kg, gavage) was administered at 5 h post reperfusion initiation and 2 h before euthanasia. Cystathionine β-synthase (CBS) inhibitor, amino-oxyacetic acid (AOAA; 10 mg/kg, i.p) was given 30 min prior to each quercetin dose.

Key findings: Quercetin reversed renal I/R induced derangements; as quercetin administration improved renal function and reversed I/R induced histopathological changes in both myocardium and kidney. Further, quercetin enhanced renal CBS content/activity, while mitigated myocardial cystathionine ɤ-lyase (CSE) content/activity as well as myocardial H₂S. On the other hand, quercetin augmented myocardial nitric oxide (NO), nuclear factor erythroid 2-related factor 2 (Nrf2) and its nuclear trasnslocation, glutamate cysteine ligase (GCL), reduced glutathione (GSH) and peroxiredoxin-2 (Prx2), while further reduced lipid peroxidation measured as malondialdehyde (MDA) as well as nuclear factor-kappa B (NF-κB), caspase-3 content and activity, and Rho-kinase activity.

Significance: Cardioprotective effects of quercetin may be mediated through regulation of Rho-kinase pathway and H₂S production.

Keywords: Hydrogen sulfide; Myocardial injury; Nrf2; Quercetin; Renal ischemia/reperfusion; Rho-kinase.