Amornpan AjjimapornShaik ShavaliManuchair EbadiPiyarat GovitrapongThe Institute of Science and Technology for Research and Development, Mahidol UniversityUniversity of North Dakota School of Medicine & Health SciencesMahidol University2018-07-122018-07-122008-12-16Brain Research Bulletin. Vol.77, No.6 (2008), 361-366036192302-s2.0-57149121900https://repository.li.mahidol.ac.th/handle/20.500.14594/19848Methamphetamine (METH) is a potent inducer of dopamine (DA) release, and is toxic to DA neurons. It has been reported that the formation of free radicals is an early signaling event that mediates cell death caused by METH. Currently, studies suggest that the generation of free radicals by oxidative catabolism of DA and dysfunction of the mitochondrial respiration chain are important mediators of neuronal death in Parkinson's disease (PD) and one process may counter the effect of the other. In our previous study, we investigated the deleterious effects of METH-induced reactive oxygen species (ROS) and mitochondrial dysfunction in dopaminergic SK-N-SH cells in culture, and assessed whether zinc-metallothionein induction provided mitochondrial protection against METH-induced mitochondrial dysfunction. Our present data demonstrate that METH enhances lipid peroxidation and mitochondrial manganese superoxide dismutase (MnSOD) enzyme levels, and decreases the antioxidant-reduced glutathione (GSH) together with an inhibition of mitochondrial complex-I activity. Pre-treatment with zinc markedly prevents the increase of lipid peroxidation and provides mitochondrial protection by scavenging free radicals via metallothionein and by increasing mitochondrial GSH and complex-I levels, thus rescuing SK-N-SH cells from METH toxicity. It should be emphasized that, however, it is still not clear that effects of METH on cultured SK-N-SH reliably model the effects of METH in the intact animal. Further studies in the intact animal are needed. © 2008 Elsevier Inc. All rights reserved.Mahidol UniversityNeuroscienceArticleSCOPUS10.1016/j.brainresbull.2008.09.006