Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring

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.

Impact of Exposure to Fenitrothion on Vital Organs in Rats

“…This might be attributed to disturbed glucose transport and glycogen metabolism [59]. Additionally, increased blood glucose level may result from an imbalance between hepatic output of glucose and its peripheral uptake [60] or as a consequence of abruptly increased catabolism to meet higher OP induced energy demands [61].…”

Regional feature extraction of various fishes based on chemical and microbial variable selection using machine learning

“…[29][30][31][32][33] Thus, it has been used extensively for analyzing biological and environmental systems. Examples include the inuence of frozen storage on sh organs, 34 exposure of shes to sewage, 35 polycyclic aromatic hydrocarbon exposure, 16 organophosphorus toxin exposure, 36 and analysis of sh eggs 37 and sh oils. 38 However, most of these studies used only one or two species and a single analytical method, and there is only limited knowledge about how this technique applies to a wider diversity of sh species.…”

Application of Passive Sampling to Characterise the Fish Exometabolome

“…Metabolomics has emerged as a powerful technique to study fish biology, including applications in toxicology [1,2,3,4], nutrition [5,6] and disease [7,8,9]. Further studies have characterised the metabolic changes associated with fundamental processes such as fish embryogenesis [10,11].…”