Crosstalk of cholinergic pathway on thyroid disrupting effects of the insecticide chlorpyrifos in zebrafish (Danio rerio)

Chlorpyrifos is a widely used organophosphate insecticide and ubiquitously detected in the environment. However, little attention has been paid to its endocrine disrupting effect to non-target organisms. In the present study, zebrafish was exposed to 13 and 65 mu g/L of chlorpyrifos for 7 and 10 days to determine the induced neurotoxidty and the alteration of thyroid metabolism. The 120 h LC50 and LC10 of chlorpyrifos was estimated as 1.35 mg/L and 0.62 mg/L based on the acute embryo toxicity assay, respectively. The acetylcholinesterase (AChE) inhibitory was detected by 13 mu g/L chlorpyrifos and could be reversed by the co-exposure of 100 and 1000 mu g/L anticholinergic agent atropine. For thyroid hormone level, 13 and 65 mu g/L of chlorpyrifos induced increased free T-3 levels in 10 dpf (days post-fertilization). The expression of thyroid related genes in 7 and 10 dpf exposed zebrafish were measured by the quantitative Real-Time PCR (qRT-PCR) assay. The mRNA expression of tshba, Barb, ttr, tpo, ugt1ab and slc5a5 had significant change. However, the alterations of thyroid hormone and mRNA expression could be partly rescued by the addition of atropine. The molecular docking of chlorpyrifos and T-3 to the thyroid receptor beta in zebrafish using homology modelling and CDOCKER procedures shown weaker binding ability of chlorpyrifos compared to T-3. Therefore, we concluded that the disturbance of thyroid signaling in zebrafish might arise from the developmental neurotoxicity induced by chlorpyrifos. (C) 2020 Published by Elsevier B.V.

Automated summary

The study suggests that chlorpyrifos can induce neurotoxicity and affect thyroid metabolism in zebrafish, including inhibition of acetylcholinesterase, alteration of thyroid hormone levels and gene expression. This effect can be partially reversed by atropine, indicating a potential mechanism for the disturbance of thyroid signaling in zebrafish.