Computational and spectrofluorimetric validation on glyphosate interactions with zebrafish (Danio rerio) acetylcholinesterase: Mechanistic and ecotoxicological implications

Abstract

This study explores the toxicodynamics of glyphosate in zebrafish (Danio rerio) acetylcholinesterase (zf-AChE) using a combined computational and experimental approach to reveal its potential cholinergic neurotoxic effects. Computational modeling suggested that glyphosate could block critical amino acid residues in the zf-AChE binding site, disrupting acetylcholine positioning and potentially leading to its pathological accumulation in cholinergic synapses. Additionally, glyphosate may adversely impact zf-AChE's flexibility, inducing conformational rigidity via hydrophobic van der Waals and hydrogen-bond interactions. These effects mirrored the binding behavior of physostigmine, a known specific zf-AChE inhibitor. Interestingly, the structural similarity between zf-AChE and human AChE (hs-AChE) suggests potential neurotoxicity in humans. Spectrofluorimetry confirmed binding between glyphosate and hs-AChE, resembling physostigmine binding. To sum up, our findings provide insights into glyphosate-induced cholinergic neurotoxicity in zebrafish, supporting extrapolations to humans and contributing valuable insights for ecotoxicology, new approach methodologies, and environmental risk assessment.