Altered metabolic pathways elucidated via untargeted in vivo toxicometabolomics in rat urine and plasma samples collected after controlled application of a human equivalent amphetamine dose.
Amphetamine
LC-HRMS/MS
Toxicometabolomics
Untargeted metabolomics
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
02
06
2021
accepted:
11
08
2021
pubmed:
21
8
2021
medline:
29
1
2022
entrez:
20
8
2021
Statut:
ppublish
Résumé
Amphetamine is widely consumed as drug of abuse due to its stimulating and cognitive enhancing effects. Since amphetamine has been on the market for quite a long time and it is one of the most commonly used stimulants worldwide, to date there is still limited information on its effects on the metabolome. In recent years, untargeted toxicometabolomics have been increasingly used to study toxicity-related pathways of such drugs of abuse to find and identify important endogenous and exogenous biomarkers. In this study, the acute effects of amphetamine intake on plasma and urinary metabolome in rats were investigated. For this purpose, samples of male Wistar rats after a single dose of amphetamine (5 mg/kg) were compared to a control group using an untargeted metabolomics approach. Analysis was performed using normal and reversed phase liquid chromatography coupled to high-resolution mass spectrometry using positive and negative ionization mode. Statistical evaluation was performed using Welch's two-sample t test, hierarchical clustering, as well as principal component analysis. The results of this study demonstrate a downregulation of amino acids in plasma samples after amphetamine exposure. Furthermore, four new potential biomarkers N-acetylamphetamine, N-acetyl-4-hydroxyamphetamine, N-acetyl-4-hydroxyamphetamine glucuronide, and amphetamine succinate were identified in urine. The present study complements previous data and shows that several studies are necessary to elucidate altered metabolic pathways associated with acute amphetamine exposure.
Identifiants
pubmed: 34414480
doi: 10.1007/s00204-021-03135-8
pii: 10.1007/s00204-021-03135-8
pmc: PMC8448701
doi:
Substances chimiques
Amino Acids
0
Biomarkers
0
Central Nervous System Stimulants
0
Amphetamine
CK833KGX7E
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3223-3234Informations de copyright
© 2021. The Author(s).
Références
Metabolomics. 2016;12:88
pubmed: 27073351
Nat Methods. 2013 Aug;10(8):755-8
pubmed: 23817071
Amino Acids. 2009 May;37(1):1-17
pubmed: 19301095
Annu Rev Biochem. 1998;67:27-48
pubmed: 9759481
Annu Rev Biochem. 2005;74:411-32
pubmed: 15952893
Life Sci. 1978 Feb;22(5):363-72
pubmed: 347211
Biomarkers. 2016 Dec;21(8):678-685
pubmed: 27328859
Metabolites. 2020 Dec 23;11(1):
pubmed: 33374857
Drug Test Anal. 2019 Jun;11(6):752-761
pubmed: 30479047
Trends Biochem Sci. 2017 Apr;42(4):274-284
pubmed: 28196646
Methods Mol Biol. 2017;1550:339-368
pubmed: 28188540
Biol Chem. 2011 Jan;392(1-2):103-15
pubmed: 21194370
Handb Exp Pharmacol. 2006;(175):485-524
pubmed: 16722247
Anal Chem. 2018 Mar 6;90(5):3156-3164
pubmed: 29381867
Front Chem. 2019 May 10;7:319
pubmed: 31134189
Metabolites. 2020 Jul 27;10(8):
pubmed: 32726975
J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Dec 1;1160:122294
pubmed: 32920479
Front Biosci. 2006 Sep 01;11:3129-48
pubmed: 16720381
Drug Metab Rev. 2000 Feb;32(1):15-44
pubmed: 10711406
Nature. 2008 Oct 23;455(7216):1054-6
pubmed: 18948945
Metabolomics. 2007 Sep;3(3):211-221
pubmed: 24039616
J Psychopharmacol. 2013 Jun;27(6):479-96
pubmed: 23539642
Drug Metab Rev. 1976;5(2):219-80
pubmed: 829898
Anal Chem. 2006 Feb 1;78(3):779-87
pubmed: 16448051
Mass Spectrom Rev. 2017 Mar;36(2):115-134
pubmed: 25881008
J Mass Spectrom. 2016 Jul;51(7):461-75
pubmed: 27434804
J Lipid Res. 2005 May;46(5):839-61
pubmed: 15722563
Arch Toxicol. 2020 Jun;94(6):2047-2059
pubmed: 32313995
RNA. 2020 Aug;26(8):910-936
pubmed: 32303649
Toxicol Lett. 2017 Mar 5;269:65-76
pubmed: 28115274
J Basic Clin Pharm. 2016 Mar;7(2):27-31
pubmed: 27057123
Nucleic Acids Res. 2007 Jan;35(Database issue):D521-6
pubmed: 17202168
Metabolites. 2020 Sep 21;10(9):
pubmed: 32967365
Arch Toxicol. 2012 Aug;86(8):1167-231
pubmed: 22392347
Arch Toxicol. 2021 Feb;95(2):509-527
pubmed: 33215236
Anal Chem. 2012 Jan 3;84(1):283-9
pubmed: 22111785
Cold Spring Harb Symp Quant Biol. 2011;76:291-8
pubmed: 22345172
J Biol Chem. 2016 Jul 15;291(29):14904-12
pubmed: 27268251
Sci Rep. 2019 Feb 26;9(1):2741
pubmed: 30808896
Trends Biochem Sci. 2007 Jan;32(1):12-9
pubmed: 17161604
Behav Pharmacol. 2018 Sep;29(6):551-556
pubmed: 29864032
J Inherit Metab Dis. 2018 May;41(3):355-366
pubmed: 29536203
Clin Pharmacokinet. 2004;43(3):157-85
pubmed: 14871155
Science. 1995 Jun 9;268(5216):1506-9
pubmed: 7770779
J Appl Toxicol. 2013 Dec;33(12):1365-83
pubmed: 23722930
J Lipid Res. 2006 Oct;47(10):2101-11
pubmed: 16902246
Front Pharmacol. 2017 Sep 07;8:617
pubmed: 28936175
Metabolomics. 2020 Mar 2;16(3):34
pubmed: 32124055
ALTEX. 2013;30(2):209-25
pubmed: 23665807
Science. 2008 Nov 7;322(5903):917
pubmed: 18988846
Drug Metab Pharmacokinet. 2016 Feb;31(1):21-26
pubmed: 26613805
Ther Drug Monit. 2002 Apr;24(2):277-89
pubmed: 11897973
Biochem J. 2004 Jun 15;380(Pt 3):715-22
pubmed: 14998372
Cell Biochem Funct. 2014 Aug;32(6):511-9
pubmed: 25042906