Mediation of FOXO3 Gene on the Momism of Quercetin Against Isoproterenol Induced Cardiotoxicity on H9c2 Cardiomyoblasts

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Shiraz University of Medical Sciences
Background: Due to over production of reactive oxygen species, oxidative stress forms one of the major reasons for progression of Cardiovascular Diseases (CVDs) and the associated cardiomyopathies. Thus, controlling these reactive radicals is one of the major management strategies for CVDs. Natural compounds and phytochemicals have already proven their potency in preventing oxidative stress and the molecular mechanism behind the action of most of these bioactive compounds is still an enigma.Objectives: The present study aimed to assess the cardioprotective effects of quercetin on isoproterenol-induced toxicity in H9c2 cardiomyoblast cells.Materials and Methods: H9C2 cells were treated with different concentrations of isoproterenol and quercetin and the cells viability was determined by Mitochondrial Tetrazolium (MTT) assay. The non-toxic concentration of quercetin was used to check its protective effect on the cells treated with 50 µM isoproterenol. Indeed, intracellular antioxidants, such as catalase, reduced glutathione (GSH), and lipid peroxidation, were determined spectrophotometrically in cell lysates. Moreover, mRNAs isolated from the treated groups were subjected to expression studies of FOXO3 and STAT3 genes by reverse transcriptase Polymerase Chain Reaction (PCR).Results: According to the results of MTT assay, the effective concentration of isoproterenol for inducing toxicity in H9c2 cells was 50 μM and the protective concentration of quercetin was 5 μm. Treatment with quercetin elicited a protective effect by enhancing the antioxidant status of the cells. This was confirmed by the decrease in peroxidation of membrane lipids, increase in catalase induction, and increase in GSH reserve. Gene expression analysis of FOXO3 and STAT3 genes revealed that the protective effect was mediated through up regulation of FOXO3 transcription factor.Conclusions: The study results signified the potential of quercetin in relieving oxidative stress and the associated cardiomyopathies.