Although the production of engineered nanoparticles increases our knowledge of toxicity and mechanisms of bioactivity during relevant exposures is lacking. In the present study mice were exposed to PbO nanoparticles (PbONP; 192.5 µg/m3; 1.93 × 106 particles/cm3) for 2, 5 and 13 weeks through continuous inhalation. The analyses addressed Pb and PbONP distribution in organs (lung, liver, kidney, brain) using electrothermal atomic absorption spectrometry and transmission electron microscopy, as well as histopathology and analyses of oxidative stress biomarkers. New LC-MS/MS methods were validated for biomarkers of lipid damage F2-isoprostanes (8-iso-prostaglandins F2-alpha and E2) and hydroxylated deoxoguanosine (8-OHdG, marker of DNA oxidation). Commonly studied malondialdehyde was also measured as TBARS by HPLC-DAD. The study revealed fast blood transport and distribution of Pb from the lung to the kidney and liver. A different Pb accumulation trend was observed in the brain, suggesting transfer of NP along the nasal nerve to the olfactory bulbs. Long-term inhalation of PbONP caused lipid peroxidation in animal brains (increased levels of TBARS and both isoprostanes). Membrane lipid damage was also detected in the kidney after shorter exposures, but not in the liver or lung. On the contrary, longer exposures to PbONP increased levels of 8-OHdG in the lung and temporarily increased lung weight after 2 and 5 weeks of exposure. The histopathological changes observed mainly in the lung and liver indicated inflammation and general toxicity responses. The present long-term inhalation study indicates risks of PbONP to both human health and the environment.

中文翻译：

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在小鼠的亚慢性吸入研究中，纳米级PbO对膜破坏和DNA损伤生物标志物的影响。

尽管工程纳米颗粒的生产增加了我们对毒性的认识，但缺乏相关暴露期间的生物活性机制。在本研究中，通过连续吸入将小鼠暴露于PbO纳米颗粒（PbONP; 192.5 µg / m3; 1.93×106颗粒/ cm3）2、5和13周。使用电热原子吸收光谱法和透射电子显微镜以及病理学和氧化应激生物标记物的分析，分析了Pb和PbONP在器官（肺，肝，肾，脑）中的分布。新的LC-MS / MS方法已验证了脂质损伤F2-异前列腺素（8-异前列腺素F2-α和E2）和羟基化脱氧鸟苷（8-OHdG，DNA氧化的标志物）的生物标志物的有效性。常用的丙二醛也通过HPLC-DAD测定为TBARS。这项研究揭示了铅从肺到肾脏和肝脏的快速血液运输和分布。在大脑中观察到了不同的Pb积累趋势，这表明NP沿着鼻神经转移到嗅球。长期吸入PbONP会引起动物脑部脂质过氧化（TBARS和两种异前列腺素的水平增加）。短时间暴露后在肾脏中也检测到膜脂质损伤，但在肝或肺中未检测到。相反，长时间接触PbONP会增加肺中8-OHdG的水平，并在接触2周和5周后暂时增加肺的重量。主要在肺和肝中观察到的组织病理学变化表明炎症和一般毒性反应。当前的长期吸入研究表明PbONP对人类健康和环境都有风险。