Effect of niclosamide on thyroid endocrine system of larval zebrafish / 中国血吸虫病防治杂志

ABSTRACT

Objective To examine the effect of niclosamide on thyroid endocrine disruption in larval zebrafish. Methods Zebrafish embryos (2 hours post-fertilization) were exposed to niclosamide at concentrations of 0, 5, 10, 20, 40 μg/L and 80 μg/L until 120 hours post-fertilization, and the body weight, hatching rate, malformation rate and survival rate of zebrafish embryos/larvae were measured. In addition, the triiodothyronine (T3) and thyroxin (T4) activities were determined in zebrafish, and the expression of tshβ and ttr genes that were associated with the regulation of thyroid hormones was quantified using a quantitative real-time PCR (qPCR) assay. Results Following exposure to niclosamide, there was no concentration-dependent hatching rate (F = 0.947, P = 0.924) or body weight of larval zebrafish (F = 1.042, P = 0.409); however, there were concentration-dependent survival rate (F = 9.309, P = 0.005) and malformation rate (F = 14.900, P = 0.001). As compared to controls, exposure to niclosamide at concentrations of 40 μg/L and 80 μg/L resulted in a significant reduction in the survival rate (both P values < 0.05), and a marked rise in the malformation rate of larval zebrafish (both P values < 0.05). In addition, the T4 activity increased (R2 = 0.927, F = 6.858, P = 0.003) and T3 activity decreased (R2 = 0.925, F = 8.212, P = 0.001) in larval zebrafish with the concentration of niclosamide. qPCR assay determined up-regulation of tshβ gene expression (R2 = 0.840, F = 9.032, P = 0.002) and down-regulation of ttr gene expression (R2 = 0.952, F = 9.130, P = 0.002). Conclusions Niclosamide exposure at environmental related concentrations may cause thyroid endocrine disruption of larval zebrafish.