title: Cardiac oxidative stress determination and myocardial morphology after a single ecstasy (MDMA) administration in a rat model.
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.
authors.affiliation: Department of Pharmacology, University of Siena, Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cerretani
authors.forename: Irene
authors.initials: I
authors.lastname: Riezzo
authors.forename: Anna Ida
authors.initials: AI
authors.lastname: Fiaschi
authors.forename: Fabio
authors.initials: F
authors.lastname: Centini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giorgi
authors.forename: Stefano
authors.initials: S
authors.lastname: D'Errico
authors.forename: Carmela
authors.initials: C
authors.lastname: Fiore
authors.forename: Steven B
authors.initials: SB
authors.lastname: Karch
authors.forename: Margherita
authors.initials: M
authors.lastname: Neri
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Pomara
authors.forename: Emanuela
authors.initials: E
authors.lastname: Turillazzi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Fineschi
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002114:Calcinosis / Q000473:pathology; D053593:Forensic Toxicology; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006213:Hallucinogens / Q000097:blood / Q000494:pharmacology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018613:Microscopy, Confocal; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D009211:Myoglobin / Q000378:metabolism; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000097:blood / Q000494:pharmacology*; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D019209:Troponin C / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism
chemical_list: D006213:Hallucinogens; D009211:Myoglobin; D019209:Troponin C; D019210:Troponin I; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D001205:Ascorbic Acid; D019803:Glutathione Disulfide