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大鼠中纯蓝藻毒素(微囊藻毒素-LR、柱孢藻毒素)诱导的潜在雌激素效应(遵循经合组织测试指南440)及甲状腺功能障碍。

Potential oestrogenic effects (following the OECD test guideline 440) and thyroid dysfunction induced by pure cyanotoxins (microcystin-LR, cylindrospermopsin) in rats.

作者信息

Casas-Rodríguez Antonio, Moyano Rosario, Molina-Hernández Verónica, Cameán Ana María, Jos Angeles

机构信息

Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor García González n°2, 41012, Seville, Spain.

Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, Facultad de Veterinaria, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Cordoba, Edificio de Sanidad Animal, Campus de Rabanales, Ctra. Madrid-Cádiz Km 396, 14014, Córdoba, Spain.

出版信息

Environ Res. 2023 Jun 1;226:115671. doi: 10.1016/j.envres.2023.115671. Epub 2023 Mar 10.

DOI:10.1016/j.envres.2023.115671
PMID:36907345
Abstract

Potential endocrine-disrupting properties of cyanotoxins, such as microcystin-LR (MC-LR) and cylindrospermopsin (CYN) are of concern due to their increasing occurrence, the scarcity of reports on the topic (particularly for CYN) and the impact of human's health at different levels. Thus, this work performed for the first time the uterotrophic bioassay in rats, following the Organization for Economic Cooperation and Development (OECD) Test Guideline 440, to explore the oestrogenic properties of CYN and MC-LR (75, 150, 300 μg/kg b.w./day) in ovariectomized (OVX) rats. Results revealed neither changes in the wet and blotted uterus weights nor in the morphometric study of uteri. Moreover, among the steroid hormones analysed in serum, the most remarkable effect was the dose-dependent increase in progesterone (P) levels in rats exposed to MC-LR. Additionally, a histopathology study of thyroids and serum levels of thyroids hormones were determined. Tissue affectation (follicular hypertrophy, exfoliated epithelium, hyperplasia) was observed, as well as increased T3 and T4 levels in rats exposed to both toxins. Taken together, these results point out that CYN and MC-LR are not oestrogenic compounds at the conditions tested in the uterotrophic assay in OVX rats, but, however, thyroid disruption effects cannot be discarded.

摘要

微囊藻毒素-LR(MC-LR)和柱孢藻毒素(CYN)等蓝藻毒素潜在的内分泌干扰特性令人担忧,这是因为它们的出现频率不断增加、关于该主题的报告稀缺(尤其是关于CYN的报告)以及对人类健康在不同层面的影响。因此,本研究首次按照经济合作与发展组织(OECD)测试指南440,在大鼠中进行子宫增重生物测定,以探究CYN和MC-LR(75、150、300μg/kg体重/天)对去卵巢(OVX)大鼠的雌激素特性。结果显示,无论是子宫湿重和吸干后重量,还是子宫形态学研究均未发生变化。此外,在分析的血清类固醇激素中,最显著的影响是暴露于MC-LR的大鼠中孕酮(P)水平呈剂量依赖性增加。另外,还对甲状腺进行了组织病理学研究并测定了血清甲状腺激素水平。观察到了组织病变(滤泡肥大、上皮脱落、增生),并且暴露于两种毒素的大鼠中T3和T4水平升高。综上所述,这些结果表明,在OVX大鼠子宫增重试验所测试的条件下,CYN和MC-LR不是雌激素化合物,但是,甲状腺干扰效应不能排除。

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