Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring
Open Access
- 16 March 2011
- journal article
- research article
- Published by American Chemical Society (ACS) in Environmental Science & Technology
- Vol. 45 (8), 3759-3767
- https://doi.org/10.1021/es103814d
Abstract
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.Keywords
Funding Information
- Wellcome Trust
This publication has 34 references indexed in Scilit:
- Discriminating between Different Acute Chemical Toxicities via Changes in the Daphnid MetabolomeToxicological Sciences, 2010
- Discovery of Metabolic Signatures for Predicting Whole Organism ToxicologyToxicological Sciences, 2010
- Chronic organophosphate (OP)-induced neuropsychiatric disorder is a withdrawal syndromeMedical Hypotheses, 2009
- Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivoAmerican Journal of Physiology-Endocrinology and Metabolism, 2009
- The organophosphorous pesticide, fenitrothion, acts as an anti-androgen and alters reproductive behavior of the male three-spined stickleback, Gasterosteus aculeatusEcotoxicology, 2008
- Uptake and elimination kinetics of a pesticide in the liver of the European EELJournal of Environmental Science and Health, Part B, 1998
- Effects of fenitrothion on survival, behavior, and brain cholinesterase activity of white‐throated sparrows (Zonotrichia albicollis)Environmental Toxicology and Chemistry, 1993
- The effect of fenitrothion on reproduction of a teleost fish,Cyprinus carpio commuais linn: A biochemical studyBulletin of Environmental Contamination and Toxicology, 1978
- The fate of fenitrothion in an aquatic ecosystemBulletin of Environmental Contamination and Toxicology, 1978
- Forest application of the insecticide fenitrothion and its effect on wild bee pollinators (Hymenoptera: Apoidea) of lowbush blueberries (Vaccinium SPP.) in Southern New Brunswick, CanadaBiological Conservation, 1975