Enzymatic-nonenzymatic cellular antioxidant defense systems response and immunohistochemical detection of MDMA, VMAT2, HSP70, and apoptosis as biomarkers for MDMA (Ecstasy) neurotoxicity.
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.
Department of Forensic Pathology, Faculty of Medicine, University of Foggia, Foggia, Italy.
Irene
I
Riezzo
Daniela
D
Cerretani
Carmela
C
Fiore
Stefania
S
Bello
Fabio
F
Centini
Stefano
S
D'Errico
Anna Ida
AI
Fiaschi
Giorgio
G
Giorgi
Margherita
M
Neri
Cristoforo
C
Pomara
Emanuela
E
Turillazzi
Vittorio
V
Fineschi
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004563:Electrochemistry / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006213:Hallucinogens / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D008315:Malondialdehyde; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000378:metabolism / Q000633:toxicity; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D018840:HSP70 Heat-Shock Proteins; D006213:Hallucinogens; D017382:Reactive Oxygen Species; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D008315:Malondialdehyde; D005978:Glutathione; D018817:N-Methyl-3,4-methylenedioxyamphetamine