Cadet J L, Ordonez S
Molecular Neuropsychiatry Section, NIH/NIDA, Intramural Research Program, Baltimore, Maryland 21224, USA.
Ann N Y Acad Sci. 2000 Sep;914:82-91. doi: 10.1111/j.1749-6632.2000.tb05186.x.
Methamphetamine (METH) has been shown to cause neurotoxic damage both in vitro and in vivo. The mechanisms of action are thought to involve the production of pathophysiologic concentration of free radicals. The present study was undertaken to assess the toxic effects of METH caused dose-dependent increased production of reactive oxygen species (ROS) and cell death. Cell death caused by METH was characterized by cytoplasmic vacuolar formation, shrinkage of cytoplasm and nuclear dissolution. Flow cytometric evaluation also revealed that this toxin causes changes similar to those observed in cells undergoing apoptosis. When taken together these observations suggest the METH can cause these cells to die via apoptosis. Further experiments indicated that growth of these cells in low (1%) serum or in the absence of serum markedly enhanced the apoptotic effects of METH. These data provide further support for the ideas that METH can cause ROS-mediated apoptosis.
甲基苯丙胺(METH)已被证明在体外和体内均可引起神经毒性损伤。其作用机制被认为涉及自由基病理生理浓度的产生。本研究旨在评估METH导致的剂量依赖性活性氧(ROS)生成增加和细胞死亡的毒性作用。METH引起的细胞死亡表现为细胞质空泡形成、细胞质收缩和核溶解。流式细胞术评估还显示,这种毒素会导致细胞发生类似于凋亡细胞所观察到的变化。综合这些观察结果表明,METH可通过凋亡导致这些细胞死亡。进一步的实验表明,这些细胞在低(1%)血清或无血清条件下生长,会显著增强METH的凋亡作用。这些数据为METH可导致ROS介导的凋亡这一观点提供了进一步的支持。