Neurotoxic effects of endosulfan on zebrafish (Danio rerio): Cognitive impairments, metallomic alterations, and impact of donepezil treatment

Endosulfan is classified as a persistent organic pollutant with a ban on use globally, yet it continues to be detected in various environmental compartments. In this study, we used technical endosulfan (with a 7:3 ratio of α-endosulfan to β-endosulfan) to assess its neurotoxic effects on aquatic organisms, particularly adult zebrafish (Danio rerio). Adult zebrafish were exposed to concentrations ranging from 0 to 2.5 μg/L for 96 h, and their power spectral density was measured using an electroencephalogram (EEG). EEG analysis revealed ictal-like activity in zebrafish exposed to 0.5 μg/L of endosulfan. At the 1.0 μg/L concentration, power spectral densities of all frequency bands increased dramatically in the endosulfan-treated zebrafish, except for the delta band, indicating cognitive impairment. This study provides the first report quantifying the neurotoxic effects of endosulfan in fish. Metallomic analysis using ICP-OES and ICP-MS revealed a significant decrease in Fe levels at 2.5 μg/L, an increase in Mo at 1 μg/L, and elevated Pb levels at both 1 and 2.5 μg/L in the endosulfan-treated zebrafish, with these elemental alterations associated with cognitive impairment. Additionally, donepezil, a drug used to treat cognitive impairment induced by scopolamine, was ineffective in alleviating endosulfan-induced cognitive impairment and even exacerbated it. Therefore, endosulfan levels should be regularly monitored in environmental matrices, especially in aquatic environments, and its metabolites should also be tested for potential negative effects on cognitive processes, due to its adverse effects observed even at sufficiently low concentrations.