Silva Marília Cordeiro Galvão da, Silva Jadson Freitas da, Santos Thamiris Pinheiro, Silva Niely Priscila Correia da, Santos Amanda Rodrigues Dos, Andrade André Lucas Corrêa de, Souza Elton Hugo Lima da Silva, Sales Cadena Marilia Ribeiro, Sá Fabrício Bezerra de, Silva Junior Valdemiro Amaro da, Cadena Pabyton Gonçalves
Departamento de Morfologia e Fisiologia Animal (DMFA), Universidade Federal Rural de Pernambuco. Av. Dom Manoel de Medeiros s/n, 52171-900, Dois Irmãos, Recife, PE, Brazil.
Departamento de Biologia (DBio), Universidade Federal Rural de Pernambuco. Av. Dom Manoel de Medeiros s/n, 52171-900, Dois Irmãos, Recife, PE, Brazil.
Chemosphere. 2019 Jan;214:330-340. doi: 10.1016/j.chemosphere.2018.09.116. Epub 2018 Sep 19.
The objective of this study was to evaluate the toxic effects of progesterone (PF) and estradiol (EF) and the effect of these steroid hormones complexed into cyclodextrins, commercially available drugs, such as micronized progesterone (PM) and transdermal estradiol (ET), and evaluate them as endocrine disruptors through biological parameters of Danio rerio. An acute toxicity test was performed with hormones using D. rerio embryos according to OECD 236 guidelines. The heart rate, mortality, and teratogenic effects were evaluated. In addition, a chronic toxicity test was assayed with adult animals for evaluation of animal behavior, reproductive capacity, and electrophysiological responses of the retina. Analysis of the results of the acute toxicity test with embryos exposed to progestins and estrogens showed that free hormones caused a higher percentage of teratogenic effects such as pericardial edema, yolk sac edema, and spinal deformation. Behavioral evaluation (30-60 days) of adult animals exposed to PM, EF, and ET demonstrated higher frequencies of aggressive behaviors such as Chase away, Persecution, Escape, and Attack. Analysis of reproductive capacity did not show significant differences in the number of viable eggs, and no significant changes were observed in the electrophysiological responses of the retina. According to these results, there is a higher toxicity effect of hormones in the free form when compared to the commercial forms and inclusion complexes. This indicates that complexation into cyclodextrin reduced the toxicity of the hormones according to the parameters studied.
本研究的目的是评估孕酮（PF）和雌二醇（EF）的毒性作用，以及这些类固醇激素与环糊精复合后的效果，环糊精复合后的产物为市售药物，如微粉化孕酮（PM）和透皮雌二醇（ET），并通过斑马鱼的生物学参数将它们评估为内分泌干扰物。根据经合组织236号指南，使用斑马鱼胚胎对激素进行了急性毒性试验。评估了心率、死亡率和致畸作用。此外，对成年动物进行了慢性毒性试验，以评估动物行为、生殖能力和视网膜的电生理反应。对暴露于孕激素和雌激素的胚胎进行急性毒性试验的结果分析表明，游离激素导致的致畸效应百分比更高，如心包水肿、卵黄囊水肿和脊柱变形。对暴露于PM、EF和ET的成年动物进行行为评估（30 - 60天），结果显示攻击性行为的频率更高，如驱赶、迫害、逃避和攻击。生殖能力分析显示，存活卵的数量没有显著差异，视网膜的电生理反应也没有观察到显著变化。根据这些结果，与市售形式和包合物相比，游离形式的激素具有更高的毒性作用。这表明，根据所研究的参数，与环糊精复合降低了激素的毒性。
