Institute for Medical Research and Occupational Health, Zagreb, Croatia.
University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
Arh Hig Rada Toksikol. 2024 Mar 29;75(1):68-75. doi: 10.2478/aiht-2024-75-3818. eCollection 2024 Mar 1.
Environmental pollution with plastic nanoparticles (PNPs) has rendered hazard assessment of unintentional human exposure to neurotherapeutic drugs through contaminated water and food ever more complicated. Due to their small size, PNPs can easily enter different cell types and cross different biological barriers, while their high surface-to-volume ratio enables higher adsorption of chemicals. This is how PNPs take the role of a Trojan horse as they enhance bioaccumulation of many different pollutants. One of the health concerns related to water pollution with neurotherapeutic drugs is endocrine disruption, already evidenced for the anticonvulsant drug carbamazepine (Cbz) and antidepressant fluoxetine (Flx). Our study aimed to evaluate endocrine disrupting effects of Cbz and Flx in mixtures with polystyrene nanoparticles (PSNPs) using the luciferase assay to measure oestrogen receptor activity in T47D-KBluc cells treated with Cbz-PSNPs or Flx-PSNPs mixtures and compare it with the activities observed in cells treated with individual mixture components (Cbz, Flx, or PSNPs). Dose ranges used in the study were 0.1-10 mg/L, 1-100 µmol/L, and 0.1-10 µmol/L for PSNPs, Cbz, and Flx, respectively. Our findings show that none of the individual components activate oestrogen receptors, while the mixtures induce oestrogen receptor activity starting with 0.1 mg/L for PSNPs, 10 µmol/L for Cbz, and 0.5 µmol/L for Flx. This is the first study to evidence that PSNPs increase oestrogen receptor activity induced by neurotherapeutic drugs at their environmentally relevant concentrations and calls for urgent inclusion of complex mixtures in health hazard assessments to inform regulatory response.
塑料纳米粒子（PNPs）对环境的污染，使得通过受污染的水和食物对非故意接触神经治疗药物的人类进行危害评估变得更加复杂。由于其粒径较小，PNPs 很容易进入不同的细胞类型并穿过不同的生物屏障，而其高的表面积与体积比使其能够吸附更多的化学物质。这就是 PNPs 充当特洛伊木马的方式，因为它们增强了许多不同污染物的生物蓄积。与神经治疗药物污染有关的健康问题之一是内分泌干扰，已被证明抗惊厥药物卡马西平（Cbz）和抗抑郁药氟西汀（Flx）存在这种情况。我们的研究旨在使用荧光素酶测定法评估 Cbz 和 Flx 与聚苯乙烯纳米粒子（PSNPs）混合物的内分泌干扰作用，以测量用 Cbz-PSNPs 或 Flx-PSNPs 混合物处理的 T47D-KBluc 细胞中的雌激素受体活性，并将其与单独处理各混合物成分（Cbz、Flx 或 PSNPs）时观察到的活性进行比较。在研究中使用的剂量范围分别为 PSNPs 为 0.1-10 mg/L、Cbz 为 1-100 µmol/L 和 Flx 为 0.1-10 µmol/L。我们的研究结果表明，没有一种单独的成分能激活雌激素受体，而混合物在 PSNPs 从 0.1 mg/L 开始、Cbz 从 10 µmol/L 开始、Flx 从 0.5 µmol/L 开始时就会诱导雌激素受体活性。这是第一项证明 PSNPs 可增加神经治疗药物在其环境相关浓度下诱导的雌激素受体活性的研究，呼吁迫切需要将复杂混合物纳入健康危害评估中，以告知监管应对措施。
