Department of Forensic Pathology, Faculty of Medicine, University of Foggia, Foggia, Italy.
J Neurosci Res. 2010 Mar;88(4):905-16. doi: 10.1002/jnr.22245.
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.
3,4-亚甲二氧基甲基苯丙胺（MDMA）诱导的神经毒性导致醌代谢物和羟自由基的形成，进而产生活性氧（ROS）。我们评估了单次 MDMA（20 mg/kg，ip）给药对给药后数小时内（<6 小时）大鼠脑不同区域的酶和非酶细胞抗氧化防御系统的影响，并在 24 小时内鉴定了 MDMA 诱导的神经毒性的形态学表达易受影响的大脑区域。MDMA 的急性给药会降低还原型和氧化型谷胱甘肽的比值，并且在 3 小时和 6 小时后，额叶皮质中的抗氧化酶活性明显降低。在纹状体、海马体和额叶皮质中，抗坏血酸水平在 3 小时和 6 小时后强烈增加。在纹状体中，丙二醛水平在 3 小时和 6 小时后以及在海马体和额叶皮质中在 6 小时后均高于对照组。对额叶、丘脑、下丘脑和纹状体区域进行了免疫组织化学研究。在额叶部分、基底神经节和丘脑观察到抗囊泡单胺转运体 2 的强烈阳性反应。只有在 24 小时后，热休克蛋白 70 才会在皮质上出现最浅层的阳性反应。
