Department of Food Science and Biotechnology, Dongguk University, Goyang, 10326, Republic of Korea.
Department of Food Science and Biotechnology, Chung-Ang University, Anseong, 17546, Republic of Korea.
Environ Pollut. 2021 Oct 1;286:117201. doi: 10.1016/j.envpol.2021.117201. Epub 2021 Apr 30.
We describe the androgen receptor (AR) agonistic/antagonistic effects of 140 veterinary drugs regulated in Republic of Korea, by setting maximum residue limits. It was conducted using two in vitro test guidelines of the Organization for Economic Cooperation and Development (OECD)-the AR-EcoScreen AR transactivation (TA) assay and the 22Rv1/MMTV_GR-KO AR TA assay. These were performed alongside the AR binding affinity assay to confirm whether their AR agonistic/antagonistic effects are based on the binding affinity to AR. Prior to conducting the AR TA assay, the proficiency test was passed the proficiency performance criterion for the AR agonist and AR antagonist assays. Among the veterinary drugs tested, four veterinary drugs (dexamethasone, trenbolone, altrenogest, and nandrolone) and six veterinary drugs (cymiazole, dexamethasone, zeranol, phenothiazine, bromopropylate, and isoeugenol) were determined as AR agonist and AR antagonist, respectively in both in vitro AR TA assays. Zeranol exhibited weak AR agonistic effects with a PC value only in the 22Rv1/MMTV_GR-KO AR TA assay. Regarding changing the AR agonistic/antagonistic effects through metabolism, the AR antagonistic activities of zeranol, phenothiazine, and isoeugenol decreased significantly in the presence of phase I + II enzymes. These data indicate that various veterinary drugs could have the potential to disrupt AR-mediated human endocrine system. Furthermore, this is the first report providing information on AR agonistic/antagonistic effects of veterinary drugs using in vitro OECD AR TA assays.
我们描述了通过设定最大残留限量来调节韩国共和国的 140 种兽医药物的雄激素受体 (AR) 激动/拮抗作用。这是使用经济合作与发展组织 (OECD) 的两项体外测试指南进行的——AR-EcoScreen AR 转录激活 (TA) 测定和 22Rv1/MMTV_GR-KO AR TA 测定。这些与 AR 结合亲和力测定一起进行，以确认它们的 AR 激动/拮抗作用是否基于与 AR 的结合亲和力。在进行 AR TA 测定之前，该测试通过了 AR 激动剂和 AR 拮抗剂测定的熟练性能标准。在所测试的兽医药物中，四种兽医药物（地塞米松、群勃龙、醋酸甲地孕酮和诺龙）和六种兽医药物（噻苯咪唑、地塞米松、玉米赤霉醇、苯并噻嗪、溴丙酯和异丁香酚）分别在两种体外 AR TA 测定中被确定为 AR 激动剂和 AR 拮抗剂。玉米赤霉醇在 22Rv1/MMTV_GR-KO AR TA 测定中仅表现出微弱的 AR 激动作用，其 PC 值仅为阳性。关于通过代谢改变 AR 激动/拮抗作用，在存在 I 期+II 期酶的情况下，玉米赤霉醇、苯并噻嗪和异丁香酚的 AR 拮抗活性显著降低。这些数据表明，各种兽医药物都有可能破坏 AR 介导的人类内分泌系统。此外，这是第一份使用体外 OECD AR TA 测定报告提供关于兽医药物的 AR 激动/拮抗作用的信息。
