Short-term oral atrazine exposure alters the plasma metabolome of male C57BL/6 mice and disrupts α -linolenate, tryptophan, tyrosine and other major metabolic pathways

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Show simple item record Lin, Zhoumeng Roede, James R. He, Chunla Jones, Dean P. Filipov, Nikolay M. 2015-05-08T20:33:43Z 2015-05-08T20:33:43Z 2015-05-08
dc.description.abstract Overexposure to the commonly used herbicide atrazine (ATR) affects several organ systems, including the brain. Previously, we demonstrated that short-term oral ATR exposure causes behavioral deficits and dopaminergic and serotonergic dysfunction in the brains of mice. Using adult male C57BL/6 mice, the present study aimed to investigate effects of a 10-day oral ATR exposure (0, 5, 25, 125, or 250 mg/kg) on the mouse plasma metabolome and to determine metabolic pathways affected by ATR that may be reflective of ATR’s effects on the brain and useful to identify peripheral biomarkers of neurotoxicity. Four h after the last dosing on day 10, plasma was collected and analyzed with high-performance, dual chromatography-Fourier-transform mass spectrometry that was followed by biostatistical and bioinformatic analyses. ATR exposure (≥5 mg/kg) significantly altered plasma metabolite profile and resulted in a dose-dependent increase in the number of metabolites with ion intensities significantly different from the control group. Pathway analyses revealed that ATR exposure strongly correlated with and disrupted multiple metabolic pathways. Tyrosine, tryptophan, linoleic acid and α-linolenic acid metabolic pathways were among the affected pathways, with α-linolenic acid metabolism being affected to the greatest extent. Observed effects of ATR on plasma tyrosine and tryptophan metabolism may be reflective of the previously reported perturbations of brain dopamine and serotonin homeostasis, respectively. ATR-caused alterations in the plasma profile of α-linolenic acid metabolism are a potential novel and sensitive plasma biomarker of ATR effect and plasma metabolomics could be used to better assess the risks, including to the brain, associated with ATR overexposure. en_US
dc.language.iso en_US en_US
dc.relation.uri en_US
dc.rights NOTICE: this is the author's version of a work that was accepted for publication in Toxicology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Toxicology, [Vol. 326, (2014)] doi:10.1016/j.tox.2014.11.001 en_US
dc.subject Atrazine en_US
dc.subject Metabolomics en_US
dc.subject Biomarker en_US
dc.subject Pesticide en_US
dc.subject Metabolic pathway analysis en_US
dc.subject Dual chromatography-Fourier-transform mass spectrometry (DC-FTMS) en_US
dc.title Short-term oral atrazine exposure alters the plasma metabolome of male C57BL/6 mice and disrupts α -linolenate, tryptophan, tyrosine and other major metabolic pathways en_US
dc.type Article (author version) en_US 2014 en_US
dc.citation.doi doi:10.1016/j.tox.2014.11.001 en_US
dc.citation.epage 141 en_US
dc.citation.jtitle Toxicology en_US
dc.citation.spage 130 en_US
dc.citation.volume 326 en_US
dc.contributor.authoreid zhoumeng en_US

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