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, F. 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 via OpenAlex
Summary
AI-generated from the abstractA single dose of MDMA (20 mg/kg) in rats rapidly disrupts the brain's antioxidant defenses within hours. Reduced and oxidized glutathione ratios decreased, and antioxidant enzyme activities fell significantly after 3 and 6 hours in the frontal cortex. Ascorbic acid levels rose sharply in the striatum, hippocampus, and frontal cortex after 3 and 6 hours. Malonaldehyde, a marker of oxidative damage, increased in the striatum after 3 and 6 hours and in the hippocampus and frontal cortex after 6 hours. Immunohistochemistry revealed strong antivesicular monoamine transporter 2 positivity in frontal sections, basal ganglia, and thalamus, and heat shock protein 70 appeared in the superficial cortical layer after 24 hours, indicating early neurotoxic changes.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat brain |
| Intervention | MDMA |
| Dose | 20 mg/kg |
| Duration | 24 hours |
| Topics | MDMA |
| Keywords | Neurotoxicity Striatum Pharmacology Antioxidant |
| Citations | 47 |
| Key finding | 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.