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

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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 Ca2 + homeostasis. The depression in Ca2+ regulatory mechanism by reactive oxygen species ultimately results in intracellular Ca2 + overload, CBN and cell death.

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Acknowledgements

This work was carried through the financial support of University of Siena, Italy (University Research Plan 2004) and Siniscalco Ceci Foundation, Banca del Monte of Foggia, Italy.

We thank Oliviero Brogi, Department of Pharmacology “G. Segre”, University of Siena, Italy for his technical assistance.

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Authors and Affiliations

  1. Department of Pharmacology “G. Segre”, University of Siena, Siena, Italy

    Daniela Cerretani, Anna Ida Fiaschi & Giorgio Giorgi

  2. Department of Forensic Pathology, University of Foggia, Ospedale Colonnello D’Avanzo, Via degli Aviatori 1, 71100, Foggia, Italy

    Irene Riezzo, Stefano D’Errico, Carmela Fiore, Margherita Neri, Cristoforo Pomara, Emanuela Turillazzi & Vittorio Fineschi

  3. Unit of Forensic Toxicology, University of Siena, Siena, Italy

    Fabio Centini

  4. Consultant Forensic Pathologist, PO Box 5139, Berkeley, CA, 94705, USA

    Steven B. Karch

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  1. Daniela Cerretani
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  2. Irene Riezzo
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  11. Emanuela Turillazzi
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Correspondence to Vittorio Fineschi.

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Cerretani, D., Riezzo, I., Fiaschi, A.I. et al. Cardiac oxidative stress determination and myocardial morphology after a single ecstasy (MDMA) administration in a rat model. Int J Legal Med 122, 461–469 (2008). https://doi.org/10.1007/s00414-008-0262-2

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  • DOI: https://doi.org/10.1007/s00414-008-0262-2

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