Protective effects of vitamin E and quercetin against MDMA-induced cardiac and hematological dysfunction in male wistar rats.

3,4-Methylenedioxymethamphetamine (MDMA), a synthetic psychoactive amphetamine derivative widely abused as the recreational drug “ecstasy,” is associated with oxidative stress–mediated cardiotoxicity and hematological disturbances. Despite documented antioxidant properties of quercetin and vitamin E individually, limited evidence exists regarding their combined protective efficacy against MDMA-induced cardiovascular dysfunction. This study evaluated the combined and complementary effects of quercetin and vitamin E on cardiac, hematological, lipid, and electrocardiographic alterations induced by MDMA in adult male Wistar rats. Thirty-five male Wistar rats (10–12 weeks old) were randomized into seven groups (n = 5 per group): Control, MDMA only (10 mg/kg/day), QUE only (50 mg/kg/day), VE only (100 mg/kg/day), MDMA + QUE, MDMA + VE, and MDMA + QUE + VE. All treatments were administered orally for 60 days. Parameters assessed include: cardiac injury markers (troponin I, LDH, CK-NAC), oxidative stress (MDA, SOD, CAT, GSH), inflammatory mediators (TNF-α, IL-1β, MPO), hematological parameters (RBC, WBC, platelets, and blood indices parameters), lipid profile (TC, TG, HDL, LDL), and myocardial histopathology. MDMA alone significantly elevated MDA, TNF-α, IL-1β, MPO, troponin I, LDH, CK-NAC, induced dyslipidemia, and caused pronounced myocardial degeneration. Neither QUE nor VE treatment alone altered baseline parameters, but each markedly attenuated MDMA-induced oxidative stress, inflammation, enzyme release, lipid abnormalities, and histological damage. The combined QUE + VE regimen produced the most comprehensive protection, nearly restoring redox homeostasis, normalizing inflammatory and injury markers, improving lipid profiles, and preserving myocardial architecture. Hematological disruptions from MDMA were also partially corrected by both antioxidants, with the greatest improvement in the combination group. Quercetin and vitamin E confer significant cardio-protective and hematological benefits against MDMA toxicity in rats. Their combined use achieves superior mitigation of oxidative stress, inflammation, lipid derangements, and myocardial injury, suggesting potential for adjunctive therapy in MDMA-related cardiotoxicity.