Regulation of Heat Shock Proteins 27 and 70, p-Akt/p-eNOS and MAPKs by Naringin Dampens Myocardial Injury and Dysfunction In Vivo after Ischemia/Reperfusion

Abstract

Naringin has antioxidant properties that could improve redox-sensitive myocardial ischemia reperfusion (IR) injury. This study was designed to investigate whether naringin restores the myocardial damage and dysfunction in vivo after IR and the mechanisms underlying its cardioprotective effects. Naringin (20–80 mg/kg/day, p.o.) or saline were administered to rats for 14 days and the myocardial IR injury was induced on 15th day by occluding the left anterior descending coronary artery for 45 min and subsequent reperfusion for 60 min. Post-IR rats exhibited pronounced cardiac dysfunction as evidenced by significantly decreased mean arterial pressure, heart rate, +LVdP/dt max (inotropic state), -LVdP/dt max (lusitropic state) and increased left ventricular end diastolic pressure as compared to sham group, which was improved by naringin. Further, on histopathological and ultrastructural assessments myocardium and myocytes appeared more normal in structure and the infarct size was reduced significantly in naringin 40 and 80 mg/kg/day group. This amelioration of post-IR-associated cardiac injury by naringin was accompanied by increased nitric oxide (NO) bioavailability, decreased NO inactivation to nitrotyrosine, amplified protein expressions of Hsp27, Hsp70, β-catenin and increased p-eNOS/eNOS, p-Akt/Akt, and p-ERK/ERK ratio. In addition, IR-induced TNF-α/IKK-β/NF-κB upregulation and JNK phosphorylation were significantly attenuated by naringin. Moreover, western blotting and immunohistochemistry analysis of apoptotic signaling pathway further established naringin cardioprotective potential as it upregulated Bcl-2 expression and downregulated Bax and Caspase-3 expression with reduced TUNEL positivity. Naringin also normalized the cardiac injury markers (lactate dehydrogenase and creatine kinase-MB), endogenous antioxidant activities (superoxide dismutase, reduced glutathione and glutathione peroxidase) and lipid peroxidation levels. Thus, naringin restored IR injury by preserving myocardial structural integrity and regulating Hsp27, Hsp70, p-eNOS/p-Akt/p-ERK signaling and inflammatory response.

Naringin ameliorates endothelial dysfunction in fructose-fed rats

“…Previous studies demonstrated that naringin elevated expression of p-eNOS (Ser1177) and reduced expression of nitrotyrosine in myocardial ischemia reperfusion injury (44). In this study, it was found that oral administration of naringin to fructose fed rats for 4 weeks increased the expression of eNOS and p-eNOS (Ser1177), and decreased the expression of nitrotyrosine in aortic tissues (Fig.…”

Febuxostat ameliorates doxorubicin-induced cardiotoxicity in rats

“…The primary antibodies used were against b-actin, caspase-3, IKK-b, NF-jBp65, TNF-a, Bax and Bcl-2 and were detected with HRP-conjugated anti-rabbit/anti-goat secondary antibody. The antibody-antigen complexes were visualized using enhanced chemiluminescence kit (Thermo Scientific) under FluorChem M Protein imaging System (Bucher Biotec AG, Basel Switzerland) and were quantified by Bio-Rad Quantity One 4.4.0 software (BIO-RAD, Hercules, CA, USA) [22].…”

Naringin protects against anoxia/reoxygenation-induced apoptosis in H9c2 cells via the Nrf2 signaling pathway

“…17 Moreover, several studies have suggested that extracellular signalregulated kinase (ERK1/2), 18 5′ AMP-activated protein kinase (AMPK), 19 phosphatidylinositol-3-kinase (PI3 K/AKT), and protein kinase C (PKC) 20 may have a central function in the activation of Nrf2. 26,29,30 However, the molecular mechanisms underlying the protective effects of Nar against anoxia/reoxygenation (A/R)-induced cardiac insult remain poorly defined. 21 Flavonoids are a group of polyphenolic compounds that are common components of the human diet.…”