Enzymatic–nonenzymatic cellular antioxidant defense systems response and immunohistochemical detection of MDMA, VMAT2, HSP70, and apoptosis as biomarkers for MDMA (Ecstasy) neurotoxicity
Journal of Neuroscience Research – October 01, 2009
Source: OpenAlex
Summary
A single dose of MDMA (20 mg/kg) significantly impacts brain chemistry within hours, leading to neurotoxicity. Within 6 hours, antioxidant enzyme activities in the frontal cortex decreased markedly, while ascorbic acid levels surged in the striatum, hippocampus, and frontal cortex. Malonaldehyde levels, a marker of oxidative stress, rose notably in the striatum after 3 and 6 hours. Immunohistochemical analysis revealed strong reactions in key brain areas, indicating severe cellular stress and potential damage from reactive oxygen species following MDMA administration.
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.