Thyroid hormone disrupting potentials of benzisothiazolinone in embryo-larval zebrafish and rat pituitary GH3 cell line

Benzisothiazolinone (BIT), one of the most widely used antimicrobial agents in consumer products, has frequently been detected in the water environment. The present study was conducted to determine the adverse effects of BIT on the thyroid neuroendocrine system of zebrafish embryos/larvae. Rat pituitary (GH3) cell line was employed to support the underlying mechanism of thyroid hormone disrupting effects. Significant coagu-lation and hatching delay were observed in embryos exposed to 30 mu g/L of BIT, which in turn remarkably decreased hatchability and larval survival. In BIT-exposed larvae, tsh beta, tshr, and trh genes were significantly upregulated along with a decrease in thyroxine and triiodothyronine content, indicating that BIT decreased thyroid hormones and increased thyrotropin-releasing hormone and thyroid stimulating hormone secretion through a feedback circuit. The downregulation of tr alpha and deio2 genes in the zebrafish larvae suggests the in-hibition of thyroid hormone receptors and deiodination. Similar to the results in zebrafish, upregulation of tsh beta and downregulation of tr alpha, tr beta, deio1, and deio2 genes were observed in GH3 cells. Our observations suggest that BIT can decrease the level of thyroid hormones by influencing central regulation, receptor binding, and deiodination.

Automated summary

In this study, the adverse effects of benzisothiazolinone (BIT) on the thyroid neuroendocrine system of zebrafish embryos/larvae were investigated. BIT exposure resulted in coagulation and hatching delay, decreased hatchability and larval survival, and altered gene expression related to thyroid hormones and thyrotropin-releasing hormone secretion. The underlying mechanisms involve central regulation, receptor binding, and deiodination.