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NAC 和 Sal 对氧化锌纳米颗粒诱导的孕鼠生殖发育毒性的保护作用。

Protective effect of the NAC and Sal on zinc oxide nanoparticles-induced reproductive and development toxicity in pregnant mice.

机构信息

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China.

Zystein, LLC., Fayetteville, AR72703, USA.

出版信息

Food Chem Toxicol. 2020 Sep;143:111552. doi: 10.1016/j.fct.2020.111552. Epub 2020 Jul 5.

DOI:10.1016/j.fct.2020.111552
PMID:32640348
Abstract

The growing use of zinc oxide nanoparticles (ZnO NPs) in various applications has raised many concerns about the potential risks to human health. In this research, the protective effects of cellular oxidative stress inhibitor N-Acetyl-cysteine (NAC) and endoplasmic reticulum (ER) stress inhibitor Salubrinal (Sal) on reproductive toxicity induced by ZnO NPs were investigated. The results showed that application of these two kinds of cell stress inhibitors after oral ingestion of ZnO NPs could prevent the weight loss of pregnant mice; reduce zinc content in the uterus, placenta and fetus; reduce abnormal development of the offspring; and decrease fetal abortion. Furthermore, RT-qPCR, Western blot and immunofluorescence assay results indicated that NAC restored the expression of Gclc, reduced the expression of ATF4, JNK and Caspase-12, and decreased the expression of eNOS and IGF-1, in the placenta. Sal decreased the expression of ATF4, JNK and Caspase-12, and increased the expression of eNOS and IGF-1caused by the oral ingestion of ZnO NPs. These results indicated that treatment with NAC and Sal after oral exposure could reduce reproductive and development toxicity caused by ZnO NPs which induced reproductive and development toxicity that was probably caused by the activation of oxide stress and ER stress.

摘要

氧化锌纳米粒子(ZnO NPs)在各种应用中的日益广泛使用引起了人们对其对人类健康潜在风险的诸多关注。在这项研究中,研究了细胞氧化应激抑制剂 N-乙酰半胱氨酸(NAC)和内质网(ER)应激抑制剂 Salubrinal(Sal)对 ZnO NPs 诱导的生殖毒性的保护作用。结果表明,口服摄入 ZnO NPs 后应用这两种细胞应激抑制剂可以防止孕鼠体重减轻;减少子宫、胎盘和胎儿中的锌含量;减少后代的异常发育;并减少胎儿流产。此外,RT-qPCR、Western blot 和免疫荧光分析结果表明,NAC 恢复了 Gclc 的表达,降低了 ATF4、JNK 和 Caspase-12 的表达,并降低了胎盘中 eNOS 和 IGF-1 的表达。Sal 降低了口服摄入 ZnO NPs 引起的 ATF4、JNK 和 Caspase-12 的表达,并增加了 eNOS 和 IGF-1 的表达。这些结果表明,口服暴露后用 NAC 和 Sal 治疗可以减轻 ZnO NPs 引起的生殖和发育毒性,这可能是由氧化应激和 ER 应激的激活引起的。

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