Metabolic Disruptions in Zebrafish Induced by α-Cypermethrin: A Targeted Metabolomics Study

TL;DR

This study uses targeted metabolomics to explore how α-cypermethrin, a pesticide, disrupts zebrafish metabolism, revealing key pathways affected by sublethal exposure.

Contribution

The study provides novel mechanistic insights into α-cypermethrin-induced metabolic disruptions in zebrafish using targeted metabolomics.

Findings

Exposure to α-cypermethrin caused dose-dependent metabolic changes in zebrafish.

Disruptions were observed in glycolysis, glycerolipid metabolism, amino acid turnover, and glutathione pathways.

Glutamate depletion and reduced GABA and TCA cycle intermediates indicate oxidative stress.

Abstract

The widespread application of pesticides in agriculture has raised increasing concerns regarding their ecological impact, particularly in aquatic environments. Among these, α-cypermethrin, a highly active isomeric form of cypermethrin, has been extensively used due to its potent insecticidal efficacy and low mammalian toxicity. However, its toxicity to non-target aquatic organisms remains insufficiently understood at the metabolic level. In this study, a targeted metabolomics approach was employed to investigate the biochemical effects of α-cypermethrin in adult zebrafish. Acute toxicity was first determined to establish sublethal exposure concentrations (0.15 µg/L and 1.5 µg/L), followed by a 48 h exposure under a controlled flow-through system. GC-MS/MS-based analysis quantified 395 metabolites, and multivariate statistical models (principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA)) revealed clear dose-dependent metabolic alterations at two time points. Pathway analysis identified disruptions in glycolysis, glycerolipid metabolism, amino acid turnover, and glutathione pathways. Notably, glutamate depletion and associated reductions in GABA (4-Aminobutanoate) and TCA (Tricarboxylic acid) cycle intermediates suggest oxidative stress-induced metabolic bottlenecks. These results provide mechanistic insights into α-cypermethrin-induced toxicity and demonstrate the utility of metabolite-level biomarkers for environmental monitoring. This study contributes to a systems-level understanding of how sublethal pesticide exposure affects vertebrate metabolism, offering a basis for improved ecological risk assessment and pesticide regulation.

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