Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China.
Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China.
Ecotoxicol Environ Saf. 2024 Sep 15;283:116777. doi: 10.1016/j.ecoenv.2024.116777. Epub 2024 Jul 24.
Lactation women, a highly concerned demographic in society, face health risks that deserve attention. Zinc oxide nanoparticles (ZnO NPs) are widely utilized in food and daily products due to their excellent physicochemical properties, leading to the potential exposure of lactating women to ZnO NPs. Hence, assessing the potential risks associated with ZnO NP exposure during lactation is critical. While studies have confirmed that exposure to ZnO NPs during lactation can induce toxic responses in multiple organs through blood circulation, the effects of lactational exposure on mammary tissue remain unclear. This research investigated the impairment of mammary tissue induced by ZnO NPs and its potential mechanisms. Through administering multiple injections of ZnO NPs into the tail vein of lactating ICR mice, our study revealed that ZnO NPs can deposit in the mammary tissues, downregulating key components of mammary epithelial barrier such as ZO-1, occludin, and claudin-3. In vivo, we also found that ZnO NPs can simultaneously induce apoptosis, necroptosis, and pyroptosis, called PANoptosis. Additionally, using EpH4-Ev cells to simulate an in vitro mammary epithelial barrier model, we observed that ZnO NPs effectively disrupted the integrity of mammary epithelial barrier and induced PANoptosis. Furthermore, we confirmed that PANoptosis was responsible for the mammary epithelial barrier disruption induced by ZnO NPs. Moreover, we identified that ZBP1 was the primary mechanism of ZnO NPs inducing PANoptosis. These discoveries are designed to enhance our comprehension of the mechanisms underlying mammary epithelial barrier disruption caused by ZnO NPs, and we aim to highlight the potential hazards associated with daily usage and therapeutic exposure to ZnO NPs during lactation.
哺乳期妇女是社会中备受关注的群体，她们面临着各种健康风险，需要引起重视。氧化锌纳米粒子（ZnO NPs）由于其优异的物理化学性质，被广泛应用于食品和日用品中，这使得哺乳期妇女可能会接触到 ZnO NPs。因此，评估哺乳期接触 ZnO NPs 所带来的潜在风险至关重要。尽管已有研究证实，哺乳期暴露于 ZnO NPs 会通过血液循环引起多个器官的毒性反应，但 ZnO NP 暴露对乳腺组织的影响尚不清楚。本研究旨在探讨 ZnO NPs 对乳腺组织的损伤作用及其潜在机制。通过向哺乳期 ICR 小鼠尾静脉多次注射 ZnO NPs，我们发现 ZnO NPs 可以沉积在乳腺组织中，下调乳腺上皮细胞屏障的关键组成部分，如 ZO-1、occludin 和 claudin-3。在体内，我们还发现 ZnO NPs 可以同时诱导细胞凋亡、坏死性凋亡和焦亡，称为 PANoptosis。此外，我们使用 EpH4-Ev 细胞模拟体外乳腺上皮细胞屏障模型，观察到 ZnO NPs 可以有效破坏乳腺上皮细胞屏障并诱导 PANoptosis。进一步证实，PANoptosis 是 ZnO NPs 诱导乳腺上皮细胞屏障破坏的主要机制。此外，我们确定 ZBP1 是 ZnO NPs 诱导 PANoptosis 的主要机制。这些发现旨在增强我们对 ZnO NPs 引起乳腺上皮细胞屏障破坏的机制的理解，并强调哺乳期日常使用和治疗性接触 ZnO NPs 所带来的潜在危害。
