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Cardiac oxidative stress determination and myocardial morphology after a single ecstasy (MDMA) administration in a rat model.

Daniela Cerretani, Irene Riezzo, Anna Ida Fiaschi, Fabio Centini, Giorgio Giorgi, Stefano D'Errico, Carmela Fiore, Steven B. Karch, Margherita Neri, Cristoforo Pomara, Emanuela Turillazzi, Vittorio Fineschi

International Journal of Legal Medicine November 2008 DOI: 10.1007/s00414-008-0262-2 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Animal experiment Peer reviewed
Population Male albino rats
Intervention MDMA
Duration Assessments at 3, 6, 16 and 24 hours after MDMA administration
Measures total glutathione (GSH), oxidised glutathione (GSSG), ascorbic acid (AA), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), malondialdehyde (MDAL), histology for contraction band necrosis, macrophage infiltration, calcium deposits
Topics MDMA
Key findings A single MDMA dose in male albino rats reduced antioxidant enzyme activity and glutathione and ascorbic acid levels while increasing malondialdehyde, indicating oxidative stress. Heart tissue showed contraction band necrosis at 6 hours, macrophage infiltration by 16 hours, and calcium deposits in cardiomyocytes, which the authors propose may result from reactive oxygen species disrupting calcium regulation and leading to cell death.

Abstract

Experimental and clinical data indicate that 3,4-methylenedioxy-N-methylamphetamine (MDMA) abuse can produce significant cardiovascular toxicity. A mechanism may be a direct toxic effect of redox active metabolites of MDMA. To evaluate the effect of a single MDMA dose on cellular antioxidant defence system and to investigate the morphology in male albino rats, total glutathione (GSH), oxidised glutathione (GSSG), ascorbic acid (AA), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and malondialdehyde (MDAL) were studied. The effects were evaluated at 3, 6, 16 and 24 h after MDMA administration. Antioxidant enzymes activity was significantly reduced: GPx (-24%) and SOD (-50%) after 3 h and GR (-19%) after 6 h from treatment. AA levels decrease (-37%) after 3 h and (-30%) after 6 h; MDAL level increased (+119%) after 3 h; GSH levels decreased after 3 (31.3%) and 6 h (37.9%) from MDMA treatment. GSSG content was not affected by ecstasy administration. Myocardial contraction band necrosis (CBN) was already visible in rats killed at 6 h. After 16 h, macrophagic monocytes around the necrotic myocardial cells were observed, and within 24 h, this infiltrate became more widespread with an early removal of the necrotic material. Calcium deposits were observed within ventricular cardiomyocytes with intact nuclei and sarcomeres. Single administration of MDMA can significantly alter the cellular antioxidant defence system and produce oxidative stress which may result in lipid peroxidation and disruption of Ca(2 +) homeostasis. The depression in Ca(2+) regulatory mechanism by reactive oxygen species ultimately results in intracellular Ca(2 +) overload, CBN and cell death.

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