Cardiac oxidative stress determination and myocardial morphology after a single ecstasy (MDMA) administration in a rat model.
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.
Cerretani
Daniela
D
Department of Pharmacology, University of Siena, Siena, Italy.
Riezzo
Irene
I
Fiaschi
Anna Ida
AI
Centini
Fabio
F
Giorgi
Giorgio
G
D'Errico
Stefano
S
Fiore
Carmela
C
Karch
Steven B
SB
Neri
Margherita
M
Pomara
Cristoforo
C
Turillazzi
Emanuela
E
Fineschi
Vittorio
V
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
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