First In Vivo Evidence for Compromised Brain Energy Metabolism upon Intranasal Exposure to ZnO Nanoparticles,Environmental Science & Technology Letters

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First In Vivo Evidence for Compromised Brain Energy Metabolism upon Intranasal Exposure to ZnO Nanoparticles
Environmental Science & Technology Letters ( IF 8.9 ) Pub Date : 2020-03-30 , DOI: 10.1021/acs.estlett.0c00176
Zhiling Guo _{1,

2,

3} , Peng Zhang ₃ , Heidi Qunhui Xie _{1,

2,

4} , Bin Zhao _{1,

2,

4} , Iseult Lynch ₃

Affiliation

Previous studies indicate that exposure to zinc oxide nanoparticles (ZnO NPs) may potentially cause brain damage in mammals; however, the mechanism remains unclear. In particular, their effect on brain energy metabolism, which is essential for maintaining brain function, is unknown. This study demonstrates that intranasal exposure to ZnO NPs causes a decrease in the relative brain weight of rats and induces structural and pathological changes in the brain. Multiomics data consistently demonstrate the alteration of energy metabolism in the brain, including upregulated glycolysis, a downregulated tricarboxylic acid cycle, and oxidative phosphorylation, as well as downregulated fatty acid β-oxidation, an alternative pathway for an energy supply. As a result, the adenosine triphosphate (ATP) levels in the brain are depressed. ZnSO₄ exposure results in similar Zn accumulation, identical Zn chemical species, and similar patterns of effects on the brain compared to ZnO NPs, suggesting that the effects observed in the ZnO NP group are mainly caused by the released Zn²⁺. This study provides the first in vivo evidence for compromised brain energy metabolism induced by ZnO NPs. Further studies are thus imperative to explore the longer-term consequences of the compromised brain energy metabolism and the origin of the toxic effects and to expand to other NPs.

中文翻译：

鼻内暴露于ZnO纳米粒子后脑能量代谢受损的首次体内证据。

先前的研究表明，暴露于氧化锌纳米颗粒（ZnO NPs）可能会引起哺乳动物的脑损伤。但是，机制尚不清楚。特别地，它们对维持脑功能必不可少的对脑能量代谢的影响尚不清楚。这项研究表明，鼻内暴露于ZnO NPs会导致大鼠相对大脑重量的减少，并诱发大脑的结构和病理变化。多元组学数据一致地证明了大脑中能量代谢的改变，包括糖酵解上调，三羧酸循环下调和氧化磷酸化，以及脂肪酸β-氧化下调（一种替代的能量供应途径）。结果，大脑中的三磷酸腺苷（ATP）水平降低。硫酸锌₄暴露导致与ZnO NPs相似的Zn积累，相同的Zn化学种类以及对大脑的相似作用模式，这表明ZnO NP组中观察到的作用主要是由释放的Zn ²⁺引起的。这项研究提供了由ZnO NPs诱导的脑能量代谢受损的第一个体内证据。因此，有必要开展进一步研究，以探索受损的脑能量代谢的长期后果以及毒性作用的起源，并扩展到其他NP。

更新日期：2020-03-30

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