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抗甲状腺药物丙硫氧嘧啶在斑马鱼部分生命周期试验中的作用。

Effects of the antithyroid agent propylthiouracil in a partial life cycle assay with zebrafish.

作者信息

van der Ven Leo T M, van den Brandhof Evert-Jan, Vos José H, Power Deborah M, Wester Piet W

机构信息

Laboratory for Toxicology, Pathology, and Genetics, RIVM, TOX 12, PO Box 1, NL-3720 BA Bilthoven, The Netherlands.

出版信息

Environ Sci Technol. 2006 Jan 1;40(1):74-81. doi: 10.1021/es050972c.

DOI:10.1021/es050972c
PMID:16433335
Abstract

Some ubiquitous pollutants of the aquatic environment, such as PCBs or other polyhalogenated aromatic hydrocarbons, may disrupt the thyroid hormone system. In a partial life cycle assay with zebrafish (Danio rerio), we studied the effects of the reference compound propylthiouracil (PTU) on reproduction, growth and development, histopathology of some target tissues, and plasma thyroid hormone levels. PTU induced a concentration-dependent increase of egg production with a concomitant decrease of mature oocyte size but had no effect on fertilization rate or hatching. In F1, serious dysmorphogenesis was found in 4 dph larvae at the highest PTU level tested (100 mg/L), and there was a dose-dependent decrease in body length and weight at 42 dph (significant at 100 mg/L PTU). At this time, there was also a decreased scale thickness, suggesting inhibited metamorphosis, detectable at 1 mg/L PTU and higher. PTU also induced activation of the thyroid follicles in a concentration-dependent way, in juveniles associated with hyperemia in the thyroid area, and depletion of liver glycogen. Effects in adults were associated with decreased circulating levels of the thyroid hormones T3 and T4. These observations indicate that disruption of the thyroid hormone system may affect the fitness of these aquatic organisms. The zebrafish model may contribute to the identification of thyroid hormone disrupting activity in water samples and also in the interpretation of histological observations in free-ranging fish species.

摘要

一些普遍存在于水生环境中的污染物,如多氯联苯或其他多卤代芳烃,可能会扰乱甲状腺激素系统。在一项对斑马鱼(Danio rerio)的部分生命周期试验中,我们研究了参考化合物丙硫氧嘧啶(PTU)对繁殖、生长和发育、某些靶组织的组织病理学以及血浆甲状腺激素水平的影响。PTU诱导产卵量呈浓度依赖性增加,同时成熟卵母细胞大小减小,但对受精率或孵化率没有影响。在F1代中,在测试的最高PTU水平(100 mg/L)下,4日龄幼虫出现严重的畸形发生,并且在42日龄时体长和体重呈剂量依赖性下降(在100 mg/L PTU时显著)。此时,鳞片厚度也有所减小,表明变态受到抑制,在1 mg/L PTU及更高水平时可检测到。PTU还以浓度依赖性方式诱导甲状腺滤泡激活,在幼鱼中与甲状腺区域充血有关,并且肝糖原耗竭。对成鱼的影响与甲状腺激素T3和T4的循环水平降低有关。这些观察结果表明,甲状腺激素系统的破坏可能会影响这些水生生物的健康状况。斑马鱼模型可能有助于识别水样中的甲状腺激素干扰活性,也有助于解释野生鱼类物种的组织学观察结果。

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