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Metabolism of a sea lamprey pesticide by fish liver enzymes part A: identification and synthesis of TFM metabolites

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Abstract

The sea lamprey (Petromyzon marinus) is a destructive invasive species in the Great Lakes that contributed to the collapse of native fish populations in the mid-1900s. 3-Trifluoromethyl-4-nitrophenol (TFM) is a selective pesticide that has been applied to sea lamprey infested tributaries of the Great Lakes to kill larvae since the 1960s and has reduced the populations by as much as 90%. However, the metabolism of TFM by sea lamprey and non-target species is not fully illuminated. Elucidation of TFM metabolism is critical for understanding its mode of action and possible environmental impact. Here, we describe the screening, identification, synthesis and structural characterization of TFM metabolites in livers from sea lamprey and three non-target species that differ in their ability to survive TFM exposure. We identified glucuronidation, sulfation, N-acetylation, glutathione conjugation, and aromatic nitro group reduction as potential detoxification mechanisms. Seven metabolites were synthesized for use as markers of TFM metabolism in fish. Quantitative 1H NMR was used to assay synthesized metabolite stock solutions that were then used as standard material to develop a quantitative LC-MS/MS method for TFM metabolites.

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Acknowledgements

This research was supported by the Great Lakes Fishery Commission. The authors thank Dr. Daniel Holmes from Michigan State University NMR core facility for his technical support. The authors also thank Andrew Paul Buchinger and Professor Kim Scribner for the gifts of fresh blue gill liver and fresh lake sturgeon liver. A.D.J. was supported by the USDA National Institute of Food and Agriculture and Hatch project MICL-02143.

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Authors and Affiliations

  1. Department of Fisheries and Wildlife, Michigan State University, 480 Wilson Rd, East Lansing, MI, 48824, USA

    Ugo Bussy, Yu-Wen Chung-Davidson, Tyler Buchinger, Ke Li & Weiming Li

  2. RTSF Mass Spectrometry and Metabolomics Core, Michigan State University, Biochemistry Building, 603 Wilson Rd, East Lansing, MI, 48824, USA

    Scott A. Smith & A. Daniel Jones

  3. Department of Biochemistry and Molecular Biology, Michigan State University, Biochemistry Building, 603 Wilson Rd, East Lansing, MI, 48824, USA

    A. Daniel Jones

  4. Department of Chemistry, Michigan State University, 578 S Shaw Lane, East Lansing, MI, 48824, USA

    A. Daniel Jones

  5. Department of Physiology, Michigan State University, 567 Wilson Rd, East Lansing, MI, 48824, USA

    Weiming Li

Authors
  1. Ugo Bussy
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  2. Yu-Wen Chung-Davidson
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  3. Tyler Buchinger
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  4. Ke Li
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  5. Scott A. Smith
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  6. A. Daniel Jones
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  7. Weiming Li
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Corresponding author

Correspondence to Weiming Li.

Ethics declarations

Animal tissues used in analyses were collected by staff of USGS Lake Huron Biological Station, Millersburg, MI 49759, USA. Experimental protocols involving the handling of fishes were carried out in accordance with United States federal guidelines for care and use of animals and were approved by the American Fisheries Society through the “Use of Fishes in Research Committee, 2014”.

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The authors declare that they have no conflict of interest.

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Bussy, U., Chung-Davidson, YW., Buchinger, T. et al. Metabolism of a sea lamprey pesticide by fish liver enzymes part A: identification and synthesis of TFM metabolites. Anal Bioanal Chem 410, 1749–1761 (2018). https://doi.org/10.1007/s00216-017-0830-8

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  • DOI: https://doi.org/10.1007/s00216-017-0830-8

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