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Lipidomic profiling of subchronic As4S4 exposure identifies inflammatory mediators as sensitive biomarkers in rats

Abstract

Arsenic sulfide compounds provide nearly all of the world's supply of arsenic. However, the risk of arsenic trisulfide exposure is still not fully investigated. Here, we systemically assessed the toxicology of As4S4 in rats by combining arsenic metabolite detection, routine testing and lipidomic profiling. It was revealed that the oral administration of As4S4 for two months increased the total arsenic contents of liver reaching saturation levels. Further analysis by anion exchange chromatography coupled with inductively coupled plasma mass spectrometry (ICP-MS) technology showed no the trace of inorganic arsenic, but the significant presence of dimethylarsinic acid (DMA), in the rat liver. This arsenic metabolite was less toxic to rats and did not induce overt liver pathology and functional injury. In contrast, lipidomic profiling provided a comprehensive map of lipids and uncovered a more complex inflammatory response, exhibiting more sensitive change to arsenic exposure. We observed that metabolites of cyclooxygenase, including PGF2α, dhk PGF2α,15k PGF2α, 8-iso-PGF2a, PGE2, dhk PGE2, PGD2, 15d-PGD2, and PGJ2, were significantly elevated. But mediators from lipoxygenase, cytochrome P450, docosahexaenoic acid, and eicosapentaenoic acid pathways were not markedly affected. In summary, we identified the DMA as predominant arsenic species in rat liver, and found cyclooxygenase-derived lipids as inflammatory mediators before the development of overt liver injury for subchronic As4S4 exposure. These mediators could translate into the potential use of metabolic biomarkers in early arsenic risk assessment and targets for therapeutic intervention.

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Supplementary files

Publication details

The article was received on 07 Jul 2018, accepted on 10 Oct 2018 and first published on 13 Oct 2018


Article type: Paper
DOI: 10.1039/C8MT00181B
Citation: Metallomics, 2018, Accepted Manuscript
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    Lipidomic profiling of subchronic As4S4 exposure identifies inflammatory mediators as sensitive biomarkers in rats

    J. Zhou, H. Ma, Y. Wu, X. Lv, J. Wang, S. Liu, D. D. Li, H. Wang, Y. Yan, N. Luo, Q. Li, H. Xu, Q. Zhang, Y. Li, H. Guo, U. Kuzmanov, L. Di, Q. Wu and J. Duan, Metallomics, 2018, Accepted Manuscript , DOI: 10.1039/C8MT00181B

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