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Metabolites 2018, 8(2), 38; https://doi.org/10.3390/metabo8020038

Untargeted Metabolomic Analysis of Rat Neuroblastoma Cells as a Model System to Study the Biochemical Effects of the Acute Administration of Methamphetamine

1
School of Veterinary and Life Sciences, Murdoch University, Perth, WA 6150, Australia
2
Separation Science and Metabolomics Laboratory, Murdoch University, Perth, WA 6150, Australia
*
Author to whom correspondence should be addressed.
Received: 30 April 2018 / Revised: 31 May 2018 / Accepted: 1 June 2018 / Published: 7 June 2018
(This article belongs to the Special Issue Metabolomics in Toxicology)
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Abstract

Methamphetamine is an illicit psychostimulant drug that is linked to a number of diseases of the nervous system. The downstream biochemical effects of its primary mechanisms are not well understood, and the objective of this study was to investigate whether untargeted metabolomic analysis of an in vitro model could generate data relevant to what is already known about this drug. Rat B50 neuroblastoma cells were treated with 1 mM methamphetamine for 48 h, and both intracellular and extracellular metabolites were profiled using gas chromatography–mass spectrometry. Principal component analysis of the data identified 35 metabolites that contributed most to the difference in metabolite profiles. Of these metabolites, the most notable changes were in amino acids, with significant increases observed in glutamate, aspartate and methionine, and decreases in phenylalanine and serine. The data demonstrated that glutamate release and, subsequently, excitotoxicity and oxidative stress were important in the response of the neuronal cell to methamphetamine. Following this, the cells appeared to engage amino acid-based mechanisms to reduce glutamate levels. The potential of untargeted metabolomic analysis has been highlighted, as it has generated biochemically relevant data and identified pathways significantly affected by methamphetamine. This combination of technologies has clear uses as a model for the study of neuronal toxicology. View Full-Text
Keywords: B50 cell line; glutamate; GC–MS; methamphetamine; neurotoxicity B50 cell line; glutamate; GC–MS; methamphetamine; neurotoxicity
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Maker, G.L.; Green, T.; Mullaney, I.; Trengove, R.D. Untargeted Metabolomic Analysis of Rat Neuroblastoma Cells as a Model System to Study the Biochemical Effects of the Acute Administration of Methamphetamine. Metabolites 2018, 8, 38.

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