Trace concentrations of a number of pharmaceutically active compounds have been detected in the aquatic environment in many countries, where they are thought to have the potential to exert adverse effects on non-target organisms. Amiodarone (AMD) is one such high-risk compound commonly used in general hospitals. AMD is known to alter normal thyroid hormone (TH) function, although little information is available regarding the specific mechanism by which this disruption occurs. Anuran tadpole metamorphosis is a TH-controlled developmental process and has proven to be useful as a screening tool for environmental pollutants suspected of disrupting TH functions. In the present study, our objective was to clarify the effects of AMD on Xenopus metamorphosis as well as to assess the bioconcentration of this pharmaceutical in the liver. We found that AMD suppressed spontaneous metamorphosis, including tail regression and hindlimb elongation in pro-metamorphic stage tadpoles, which is controlled by endogenous circulating TH, indicating that AMD is a TH antagonist. In transgenic X. laevis tadpoles carrying plasmid DNA containing TH-responsive element (TRE) and a 5′-upstream promoter region of the TH receptor (TR) βA1 gene linked to a green fluorescent protein (EGFP) gene, triiodothyronine (T₃) exposure induced a strong EGFP expression in the hind limbs, whereas the addition of AMD to T₃ suppressed EGFP expression, suggesting that this drug interferes with the binding of T₃ to TR, leading to the inhibition of TR-mediated gene expression. We also found AMD to be highly bioconcentrated in the liver of pro-metamorphic X. tropicalis tadpoles, and we monitored hepatic accumulation of this drug using mass spectrometry imaging (MSI). Our findings suggest that AMD imposes potential risk to aquatic wildlife by disrupting TH homeostasis, with further possibility of accumulating in organisms higher up in the food chain.

在许多国家的水生环境中已检测到痕量浓度的多种药物活性化合物，据认为这些物质可能对非目标生物产生不利影响。胺碘酮（AMD）是综合医院中常用的一种此类高风险化合物。众所周知，AMD能改变正常的甲状腺激素（TH）功能，尽管关于这种破坏发生的具体机制的信息很少。Anuran meta变态是TH控制的发育过程，已被证明可作为怀疑怀疑破坏TH功能的环境污染物的筛选工具。在本研究中，我们的目的是阐明AMD对非洲爪蟾的影响变态以及评估这种药物在肝脏中的生物浓度。我们发现AMD抑制了自变态，包括变态阶段t中的尾巴退缩和后肢伸长，这是由内源性循环TH控制的，表明AMD是TH拮抗剂。在携带含有TH反应元件（TRE）和TH受体（TR）βA1基因5'上游启动子区域的质粒DNA的转基因X. laevis t中，该基因与绿色荧光蛋白（EGFP）基因相连，三碘甲腺氨酸（T ₃）暴露诱导后肢中强烈的EGFP表达，而在T _3中添加AMD会抑制EGFP表达，表明该药物干扰T ₃的结合到TR，导致抑制TR介导的基因表达。我们还发现AMD在原变质热带X. t的肝脏中高度生物富集，并使用质谱成像（MSI）监测了该药物在肝脏中的蓄积。我们的研究结果表明，AMD通过破坏TH体内稳态而对水生野生生物构成潜在风险，并有可能在食物链中较高的生物体内积累。