Changes in the liver proteome of zebrafish (Danio rerio) exposed to glyphosate and aminomethylphosphonic acid in the presence of a humic substance

Herbicide exposure can pose a considerable threat to non-target aquatic animals. We aimed to study changes in the liver proteome of a model cyprinid fish species, zebrafish Danio rerio, to provide a molecular basis for the adverse effects of environmentally relevant concentrations of glyphosate (100 μg/L), its breakdown product aminomethylphosphonic acid (AMPA; 100 μg/L), and a mixture of both (50 + 50 μg/L) in the presence of humic acid (20 mg/L), which simulated a component of natural organic matter in the aquatic environment. Proteomic analysis was performed by means of high-performance liquid chromatography–tandem mass spectrometry employing a label-free quantification approach. The results present molecular evidence of the stress responses and disturbance of primary metabolic processes such as immune response, dysregulation in DNA repair, necroptosis and apoptosis signaling pathways, oxidative phosphorylation, cholesterol, lipoprotein, and carbohydrate metabolism. We registered the synergistic effect of the glyphosate and AMPA co-exposure, which was expressed in a substantial increase in the number of dysregulated proteins compared to the solo treatments. Humic acid alleviated the effects of glyphosate and its mixture with AMPA and aggravated the impact of AMPA exposure. RuvB-like 2, a protein taking part in DNA repair, and EIF2S1, involved in the regulation of stress-induced gene expression, were downregulated in the liver of zebrafish from all treatments. [Display omitted] •Environmental concentrations of glyphosate and AMPA induced stress responses in fish.•Glyphosate and AMPA co-exposure caused a synergistic effect.•Glyphosate and AMPA interfered with primary metabolic processes.•Humic acid alleviated protein dysregulation by glyphosate and its mixture with AMPA.•Humic acid aggravated protein dysregulation by AMPA.