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Enzymatic–nonenzymatic cellular antioxidant defense systems response and immunohistochemical detection of MDMA, VMAT2, HSP70, and apoptosis as biomarkers for MDMA (Ecstasy) neurotoxicity

Irene Riezzo, Daniela Cerretani, Carmela Fiore, Stefania Bello, Fabio Centini, Stefano D’errico, Anna Ida Fiaschi, Giorgio Giorgi, Margherita Neri, Cristoforo Pomara, Emanuela Turillazzi, Vittorio Fineschi

Journal of Neuroscience Research October 1, 2009 DOI: 10.1002/jnr.22245 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Rat brain
Intervention MDMA
Dose 20 mg/kg
Duration 24 hours
Topics MDMA
Keywords Neurotoxicity Striatum Pharmacology Antioxidant Dopamine Hippocampus Glutathione Endocrinology Biochemistry
Citations 47
Key findings Acute MDMA administration rapidly reduces antioxidant defenses and induces oxidative stress and early neurotoxic markers in rat brain regions within 6 to 24 hours.

Abstract

Abstract 3,4‐Methylenedioxymethamphetamine (MDMA)‐induced neurotoxicity leads to the formation of quinone metabolities and hydroxyl radicals and then to the production of reactive oxygen species (ROS). We evaluated the effect of a single dose of MDMA (20 mg/kg, i.p.) on the enzymatic and nonenzymatic cellular antioxidant defense system in different areas of rat brain in the early hours (<6 hr) of the administration itself, and we identified the morphological expressions of neurotoxicity induced by MDMA on the vulnerable brain areas in the first 24 hr. The acute administration of MDMA produces a decrease of reduced and oxidized glutathione ratio, and antioxidant enzyme activities were significantly reduced after 3 hr and after 6 hr in frontal cortex. Ascorbic acid levels strongly increased in striatum, hippocampus, and frontal cortex after 3 and 6 hr. High levels of malonaldehyde with respect to control were measured in striatum after 3 and 6 hr and in hippocampus and frontal cortex after 6 hr. An immunohistochemical investigation on the frontal, thalamic, hypothalamic, and striatal areas was performed. A strong positive reaction to the antivesicular monoamine transporter 2 was observed in the frontal section, in the basal ganglia and thalamus. Cortical positivity, located in the most superficial layer was revealed only for heat shock protein 70 after 24 hr. © 2009 Wiley‐Liss, Inc.

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