Chronic Exposure to an Environmentally Relevant Mixture of Endocrine Disruptors Alters Nuclear Phenotype and Induces Renal Fibrosis in Rats

IF 3.2 3区 医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2025-02-27 DOI:10.1002/tox.24502
Karianne Delalibera Hinokuma, Maria Luiza Silva Ricardo, Andreia Yuri Yoshigae, Thaina Cavalleri Sousa, Letícia Pereira de Souza, Gisele Alborghetti Nai, Glaura Scantamburlo Alves Fernandes, Ivana Regina da Costa, Thiago Rentz Ferreira Laginski, Leonardo de Oliveira Mendes
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Abstract

The exposome is considered an assessment of environmental exposure and associated biological responses over an individual's lifetime. Endocrine disruptors chemicals (EDCs), an important component of such exposures, exert adverse effects on human health. The kidneys are targets for EDCs because of their characteristic of bioaccumulation. Therefore, we aimed to evaluate cellular and tissue changes in the kidneys of rats exposed to an EDCs mixture (EDCs Mix). Pregnant female Sprague–Dawley rats were divided into: Control group, administered vehicle (corn oil) via gavage; EDCs mix group, administered 32.11 mg/kg/day of a mixture of 12 EDCs diluted in corn oil (2 mL/kg) via gavage. Pregnant or lactating rats received the treatment from Gestational Day 7 until Postnatal Day (DPN) 21. The male pups continued to receive the complete EDCs mix until DPN220, when they were euthanized. Nuclear alterations depended on the compartment evaluated, with the EDCs mix favoring the presence of elliptical nuclei in the cortical and glomerular regions and more rounded nuclei in the medullary region. The EDCs mix increased renal fibrosis in all compartments without altering antioxidant enzymes activity. Therefore, we conclude that environmentally relevant exposure to an EDCs mix causes nuclear changes and induces renal fibrosis.

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长期暴露于环境相关的内分泌干扰物混合物会改变大鼠的核表型并诱导肾纤维化。
暴露量被认为是对个人一生中环境暴露和相关生物反应的评估。内分泌干扰物(EDCs)是此类接触的一个重要组成部分,对人体健康产生不利影响。由于EDCs具有生物蓄积的特点,肾脏成为EDCs的靶点。因此,我们旨在评估暴露于EDCs混合物(EDCs混合物)的大鼠肾脏的细胞和组织变化。将妊娠雌性Sprague-Dawley大鼠分为:对照组,灌胃给药玉米油;EDCs混合组,12种EDCs用玉米油稀释后(2 mL/kg)混合,灌胃32.11 mg/kg/d。妊娠或哺乳期大鼠从妊娠第7天至产后第21天接受治疗。雄性幼崽继续接受完整的EDCs混合,直到DPN220,当它们被安乐死时。核改变取决于所评估的隔室,EDCs混合倾向于在皮质和肾小球区域出现椭圆核,在髓质区域出现更圆的核。EDCs混合物在不改变抗氧化酶活性的情况下增加了肾各室的纤维化。因此,我们得出结论,环境相关暴露于EDCs混合物会导致核改变并诱导肾纤维化。
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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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