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Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring
[Image: see text] The ability of targeted and nontargeted metabolomics to discover chronic ecotoxicological effects is largely unexplored. Fenitrothion, an organophosphate pesticide, is categorized as a “red list” pollutant, being particularly hazardous to aquatic life. It acts primarily as a cholin...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076994/ https://www.ncbi.nlm.nih.gov/pubmed/21410251 http://dx.doi.org/10.1021/es103814d |
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author | Southam, Andrew D. Lange, Anke Hines, Adam Hill, Elizabeth M. Katsu, Yoshinao Iguchi, Taisen Tyler, Charles R. Viant, Mark R. |
author_facet | Southam, Andrew D. Lange, Anke Hines, Adam Hill, Elizabeth M. Katsu, Yoshinao Iguchi, Taisen Tyler, Charles R. Viant, Mark R. |
author_sort | Southam, Andrew D. |
collection | PubMed |
description | [Image: see text] The ability of targeted and nontargeted metabolomics to discover chronic ecotoxicological effects is largely unexplored. Fenitrothion, an organophosphate pesticide, is categorized as a “red list” pollutant, being particularly hazardous to aquatic life. It acts primarily as a cholinesterase inhibitor, but evidence suggests it can also act as an androgen receptor antagonist. Whole-organism fenitrothion-induced toxicity is well-established, but information regarding target and off-target molecular toxicities is limited. Here we study the molecular responses of male roach (Rutilus rutilus) exposed to fenitrothion, including environmentally realistic concentrations, for 28 days. Acetylcholine was assessed in brain; steroid metabolism was measured in testes and plasma; and NMR and mass spectrometry-based metabolomics were conducted on testes and liver to discover off-target toxicity. O-demethylation was confirmed as a major route of pesticide degradation. Fenitrothion significantly depleted acetylcholine, confirming its primary mode of action, and 11-ketotestosterone in plasma and cortisone in testes, showing disruption of steroid metabolism. Metabolomics revealed significant perturbations to the hepatic phosphagen system and previously undocumented effects on phenylalanine metabolism in liver and testes. On the basis of several unexpected molecular responses that were opposite to the anticipated acute toxicity, we propose that chronic pesticide exposure induces an adapting phenotype in roach, which may have considerable implications for interpreting molecular biomarker responses in field-sampled fish. |
format | Text |
id | pubmed-3076994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-30769942011-04-14 Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring Southam, Andrew D. Lange, Anke Hines, Adam Hill, Elizabeth M. Katsu, Yoshinao Iguchi, Taisen Tyler, Charles R. Viant, Mark R. Environ Sci Technol [Image: see text] The ability of targeted and nontargeted metabolomics to discover chronic ecotoxicological effects is largely unexplored. Fenitrothion, an organophosphate pesticide, is categorized as a “red list” pollutant, being particularly hazardous to aquatic life. It acts primarily as a cholinesterase inhibitor, but evidence suggests it can also act as an androgen receptor antagonist. Whole-organism fenitrothion-induced toxicity is well-established, but information regarding target and off-target molecular toxicities is limited. Here we study the molecular responses of male roach (Rutilus rutilus) exposed to fenitrothion, including environmentally realistic concentrations, for 28 days. Acetylcholine was assessed in brain; steroid metabolism was measured in testes and plasma; and NMR and mass spectrometry-based metabolomics were conducted on testes and liver to discover off-target toxicity. O-demethylation was confirmed as a major route of pesticide degradation. Fenitrothion significantly depleted acetylcholine, confirming its primary mode of action, and 11-ketotestosterone in plasma and cortisone in testes, showing disruption of steroid metabolism. Metabolomics revealed significant perturbations to the hepatic phosphagen system and previously undocumented effects on phenylalanine metabolism in liver and testes. On the basis of several unexpected molecular responses that were opposite to the anticipated acute toxicity, we propose that chronic pesticide exposure induces an adapting phenotype in roach, which may have considerable implications for interpreting molecular biomarker responses in field-sampled fish. American Chemical Society 2011-03-16 2011-04-15 /pmc/articles/PMC3076994/ /pubmed/21410251 http://dx.doi.org/10.1021/es103814d Text en Copyright © 2011 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. |
spellingShingle | Southam, Andrew D. Lange, Anke Hines, Adam Hill, Elizabeth M. Katsu, Yoshinao Iguchi, Taisen Tyler, Charles R. Viant, Mark R. Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring |
title | Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring |
title_full | Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring |
title_fullStr | Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring |
title_full_unstemmed | Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring |
title_short | Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring |
title_sort | metabolomics reveals target and off-target toxicities of a model organophosphate pesticide to roach (rutilus rutilus): implications for biomonitoring |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076994/ https://www.ncbi.nlm.nih.gov/pubmed/21410251 http://dx.doi.org/10.1021/es103814d |
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