Department of Toxicology, Medical University of Lodz, Muszynskiego 1, 90-151, Lodz, Poland.
Department of Toxicology, Medical University of Lodz, Muszynskiego 1, 90-151, Lodz, Poland.
Chemosphere. 2024 Jul;359:142373. doi: 10.1016/j.chemosphere.2024.142373. Epub 2024 May 17.
The persistent organic pollutants (POPs) defined by the Stockholm Convention include polychlorinated naphthalenes (PCNs); of these, the most toxic, persistent, abundant, dioxin-like congeners found in human tissues are the hexachloronaphthalenes (HxCNs). Recent research also indicates that PCNs may disrupt hormonal homeostasis. The aim of this study was to evaluate the (anti)androgenic action of HxCN. Immature, castrated male Wistar rats were exposed per os to HxCN in corn oil at daily doses ranging from 0.3 to 3.0 mg kg for 10 days. According to the OECD 441 protocol (Hershberger Bioassay), the anti-androgenic assay groups were co-exposed with testosterone propionate (TP), while the androgenic groups were not. TP was used as the reference androgen (subcutaneous daily doses of 0.4 mg kg), and flutamide (FLU) as the reference antiandrogen (per os daily doses of 3.0 mg kg). Five assessory sex tissues (ASTs) were weighed: ventral prostate, seminal vesicles, levator ani-bulbocavernosus muscle (LABC), Cowper's glands and glans penis. HxCN + TP significantly decreased the weight of the ventral prostate and seminal vesicle indicating an anti-androgenic action via 5α-reductase inhibition. These weight changes were also accompanied by abnormalities in cell morphology and hormonal disturbances: lowered levels of the testosterone and thyroid hormones thyroxine and triiodothyronine. Disturbances were also noted in the lipid profile, viz. total cholesterol, triglycerides and high-density lipoprotein and non-HDL fraction content. However, the direction of these changes differed depending on the size of the HxCN dose. No dose-effect relationship was noted for most of the obtained results; as such, exposure to even small HxCN doses run the risk of anti-androgenic effects in the general population, especially when encountered in combination with other POPs and endocrine-disrupting chemicals in the environment.
持久性有机污染物（POPs）是《斯德哥尔摩公约》所定义的，其中包括多氯萘（PCNs）；在这些物质中，在人体组织中发现的最具毒性、持久性和丰富性的二噁英类似物是六氯萘（HxCNs）。最近的研究还表明，PCNs 可能会破坏激素平衡。本研究旨在评估 HxCN 的（抗）雄激素作用。将未成熟去势雄性 Wistar 大鼠经口暴露于玉米油中的 HxCN 中，每天剂量范围为 0.3 至 3.0mg/kg，共 10 天。根据 OECD 441 协议（Hershberger 生物测定法），抗雄激素测定组与丙酸睾酮（TP）共同暴露，而雄激素组则没有。TP 被用作参考雄激素（皮下每天剂量为 0.4mg/kg），氟他胺（FLU）被用作参考抗雄激素（每天口服剂量为 3.0mg/kg）。测量了五种附属性性组织（ASTs）的重量：前列腺、精囊、会阴部肛提肌-球海绵体肌（LABC）、考珀氏腺和阴茎龟头。HxCN+TP 显著降低了前列腺和精囊的重量，表明通过 5α-还原酶抑制产生了抗雄激素作用。这些重量变化还伴有细胞形态异常和激素紊乱：降低了睾酮和甲状腺激素甲状腺素和三碘甲状腺原氨酸的水平。脂质谱也出现紊乱，即总胆固醇、甘油三酯和高密度脂蛋白和非高密度脂蛋白部分含量。然而，这些变化的方向取决于 HxCN 剂量的大小。大多数获得的结果没有剂量-效应关系；因此，即使接触较小剂量的 HxCN，也会使普通人群面临抗雄激素作用的风险，尤其是当它们与环境中的其他 POPs 和内分泌干扰化学物质一起接触时。
