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内分泌干扰化学物质:主题介绍。

Endocrine-Disrupting Chemicals: Introduction to the Theme.

机构信息

Interdisciplinary Department of Medicine-Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari "Aldo Moro", School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Italy.

Clinical Nutrition Unit, Medical Oncology, Department of Internal Medicine and Clinical Oncology, University of Bari, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Italy.

出版信息

Endocr Metab Immune Disord Drug Targets. 2022 Aug 15;22(7):677-685. doi: 10.2174/1871530321666210413124425.

Abstract

BACKGROUND

Endocrine-disrupting chemicals (EDCs) are natural or synthetic compounds deriving from different human activities and are widely spread into the environment, contributing to indoor and outdoor pollution. EDCs may be conveyed by food and water consumption and skin, airways, placental, and breastfeeding. Upon entering the circulation, they can interfere with endocrine system homeostasis by several mechanisms.

AIM

In this narrative review, the authors overviewed the leading mechanisms by which EDCs interact and disrupt the endocrine system, leading to possible human health concerns.

RESULTS

The leading mechanisms of EDCs-related toxicity have been illustrated in in vitro studies and animal models and may be summarized as follows: receptor agonism and antagonism; modulation of hormone receptor expression; interference with signal transduction in hormone-responsive cells; epigenetic modifications in hormone-producing or hormone-responsive cells; interference with hormone synthesis; interference with hormone transport across cell membranes; interference with hormone metabolism or clearance; interference with the destiny of hormone-producing or hormone- responsive cells.

DISCUSSION

Despite these well-defined mechanisms, some limitations do not allow for conclusive assumptions. Indeed, epidemiological and ecological studies are currently lacking and usually refer to a specific cluster of patients (occupational exposure). Methodological aspects could further complicate the issue since these studies could require a long time to provide useful information. The lack of a real unexposed group in environmental conditions, possible interference of EDCs mixture on biological results, and unpredictable dose-response curves for some EDCs should also be considered significant limitations.

CONCLUSION

Given these limitations, specific observational and long-term studies are needed to identify at-risk populations for adequate treatment of exposed patients and effective prevention plans against excessive exposure to EDCs.

摘要

背景

内分泌干扰化学物质(EDCs)是源自人类各种活动的天然或合成化合物,广泛分布于环境中,导致室内外污染。EDCs 可通过食物和水的摄入以及皮肤、呼吸道、胎盘和母乳喂养进行传递。进入循环后,它们可通过多种机制干扰内分泌系统的稳态。

目的

在本篇综述中,作者概述了 EDCs 相互作用和破坏内分泌系统的主要机制,以及可能对人类健康造成的影响。

结果

EDCs 相关毒性的主要机制已在体外研究和动物模型中得到阐明,可以概括如下:受体激动剂和拮抗剂;激素受体表达的调节;激素反应细胞信号转导的干扰;产生激素或激素反应细胞的表观遗传修饰;激素合成的干扰;跨细胞膜的激素转运干扰;激素代谢或清除的干扰;产生激素或激素反应细胞的命运干扰。

讨论

尽管存在这些明确的机制,但一些局限性不允许得出明确的结论。实际上,目前缺乏流行病学和生态学研究,并且通常仅涉及特定的患者群体(职业暴露)。方法学方面可能会进一步使问题复杂化,因为这些研究可能需要很长时间才能提供有用的信息。在环境条件下缺乏真正的未暴露群体、EDCs 混合物对生物结果的可能干扰以及某些 EDCs 不可预测的剂量-反应曲线,也应被视为重大局限性。

结论

鉴于这些局限性,需要进行特定的观察性和长期研究,以确定高危人群,并为暴露患者制定适当的治疗和针对过度暴露于 EDCs 的有效预防计划。

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