Serum withdrawal potentiates the toxic effects of methamphetamine in vitro.
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.
Cadet
J L
JL
Molecular Neuropsychiatry Section, NIH/NIDA, Intramural Research Program, Baltimore, Maryland 21224, USA. jcadet@intra.nida.nih.gov
Ordonez
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002460:Cell Line; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D066298:In Vitro Techniques; D008636:Mesencephalon / Q000166:cytology; D008694:Methamphetamine / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D044967:Serum / Q000378:metabolism*; D013997:Time Factors
D000697:Central Nervous System Stimulants; D017382:Reactive Oxygen Species; D008694:Methamphetamine