ABSTRACT: Antibiotics have been commonly used as antimicrobial agents in the process of aquaculture worldwide. However, very few studies are available on the endocrine disruption-related health risks brought about by antibiotic residues from human consumption of aquatic products. Nuclear hormone receptors (NHRs) could mediate many endocrine-disrupting activities. Therefore, in the present study, a reverse docking method was used to predict the direct binding interactions between 16 NHR conformations and 15 common antibiotics in aquaculture, thereby determining their potential endocrine-disrupting risks. To reach a compromise between the extremely scarce experimental data and an urgent need for distinguishing antibiotics of high concern with potential food-borne endocrine-disrupting risks in aquaculture, a risk-ranking system was then developed based on a comprehensive risk score for each category of antibiotics, which was the sum of the products of endocrine-disrupting potential coefficients and annual usages of antibiotics in aquaculture. The results indicated that 15% of 224 docking simulations showed a relatively high probability of binding. Sulfonamides seemed to possess the greatest endocrine-disrupting potential. The antagonistic conformation of the androgen receptor was the most susceptible NHR conformation. The rank orders of the endocrine-disrupting risk of different categories of antibiotics varied greatly from country to country, which were significantly affected by the annual usage. These findings pose questions regarding public health and safety associated with human consumption of antibiotic-containing aquatic products. In addition, we provide an approach to rank antibiotics for a specific country or region, with respect to their potential endocrine-disrupting activity, that can be used to inform regulation and prioritize experimental verification.

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水产养殖中抗生素与核激素受体之间相互作用的计算机评估

【摘要】：抗生素是世界范围内水产养殖过程中常用的抗菌剂。然而，关于人类食用水产品中的抗生素残留带来的内分泌干扰相关健康风险的研究很少。核激素受体 (NHR) 可以介导许多内分泌干扰活动。因此，在本研究中，采用反向对接方法来预测水产养殖中 16 种 NHR 构象与 15 种常见抗生素之间的直接结合相互作用，从而确定其潜在的内分泌干扰风险。为了在极其稀缺的实验数据和迫切需要将高度关注的抗生素与水产养殖中潜在的食源性内分泌干扰风险区分开来之间达成折衷，然后根据各类抗生素的综合风险评分开发了一个风险排名系统，该评分是内分泌干扰潜在系数和水产养殖中抗生素年使用量的乘积之和。结果表明，224 次对接模拟中有 15% 显示出相对较高的结合概率。磺胺类药物似乎具有最大的内分泌干扰潜力。雄激素受体的拮抗构象是最敏感的 NHR 构象。不同类别抗生素的内分泌干扰风险排序因国而异，受年使用量影响显着。这些发现对与人类食用含抗生素水产品相关的公共健康和安全提出了质疑。此外，