Quercetin inhibits the expression of MYC and CYP2E1 and reduces oxidative stress in the myocardium of spontaneously hypertensive rats

Abstract

Oxidative stress is one of the most important pathological processes in chronic heart failure caused by hypertension. These processes involve MYC-regulated mechanisms, including the induction of CYP2E1 as a potent prooxidant factor. In this work, we used qPCR, Western blot analysis, and biochemical markers of oxidative stress to investigate the ability of quercetin to inhibit oxidative stress by modulating MYC expression. We studied spontaneously hypertensive rats (SHRs) in which the onset of cardiac pathology was observed at least at 4 months of age and the development of pathology occurred during life up to 22 months of age. Wistar rats were used as normotensive controls. We observed overexpression of the transcription factor MYC (p=0.0024) in the myocardium of SHRs compared to normotensive controls, and an increased expression of MYC-target gene, CYP2E1, (p=0.0001) in the old SHR group compared to young SHRs. This probably contributed significantly to the development of oxidative stress in the cardiac tissue of old SHRs. We demonstrated that long-term treatment of old SHRs with quercetin resulted in dramatic inhibition of MYC (p=0.0000), and a significant decrease in CYP2E1 (p=0.0001) expression and CYP2E1 protein levels (p=0.0136). This probably contributed significantly to the decrease in lipid peroxidation (p=0.0000). Quercetin was also able to activate antioxidant activity, resulting in a significant improvement in the prooxidant-antioxidant balance in the heart. In turn, the elimination of oxidative stress could contribute to a decrease in blood pressure (p=0.0000) and relative heart weight (p=0.0071) in quercetin-treated old SHRs compared to the untreated old SHR group.

Longevity Spinach (Gynura procumbens) Ameliorated Oxidative Stress and Inflammatory Mediators in Cisplatin‐Induced Organ Dysfunction in Rats: Comprehensive in vivo and in silico Studies

“…A study demonstrated that quercetin significantly declines oxidative stress by reducing the expression of CYP2E1 resulting in diminish lipid peroxidation or free radical generation. [76] The other three compounds also showed favorable docking scores with CYP2E1. The regulation of hepatic CYP2E1's physiological expression is principally governed by the transcription factors hepatocyte nuclear factor-alpha (HNF-α) and NF-kB in the context of inflammatory conditions.…”

“…The protein‐ligand interaction image presented shows quercetin forms hydrogen bonds with three residues, Val388, Asn220, and Asp102, of CYP2E1 (Supplementary file). A study demonstrated that quercetin significantly declines oxidative stress by reducing the expression of CYP2E1 resulting in diminish lipid peroxidation or free radical generation [76] . The other three compounds also showed favorable docking scores with CYP2E1.…”

MYC: there is more to it than cancer

“…The myocardium of spontaneously hypertensive rats (SHRs) overexpresses MYC and its downstream target CYP2E1, whose overexpression leads to oxidative stress and other pathological processes. Long-term treatment with quercetin, a flavonoid with potential cardiovascular beneficial effects, resulted in a significant reduction of blood pressure with concomitant downregulation of MYC and CYP2E1, significantly improving the prooxidant-antioxidant profile ( Maksymchuk et al, 2023 ). Whether downregulation of MYC alone would reduce blood pressure, CYP2E1 expression, and curb the oxidative stress, still remains to be seen.…”

Alcohol, White Adipose Tissue, and Brown Adipose Tissue: Mechanistic Links to Lipogenesis and Lipolysis

“…In the case of high-density microsomes obtained from rats exposed to ethanol, a reduced GSH/GSSG ratio of 2.9:1 was observed, indicating an elevated level of oxidative stress following ethanol consumption [162]. The increased oxidative stress was associated with the up-regulated expression of CYP2E1, as demonstrated by the presence of 4-hydroxynonenal (4-HNE) protein adducts in adipocytes and an elevation in ADIPO carbonylation [163][164][165][166]. While overexpression of CYP2E1 in 3T3-L1 adipocytes did not affect intracellular ADIPO concentration [161], ethanol culture did lead to the inhibition of ADIPO release into the extracellular medium.…”