Discovery of unique and ENM- specific pathophysiologic pathways: Comparison of the translocation of inhaled iridium nanoparticles from nasal epithelium versus alveolar epithelium towards the brain of rats.
Discovery of unique and ENM- specific pathophysiologic pathways: Comparison of the translocation of inhaled iridium nanoparticles from nasal epithelium versus alveolar epithelium towards the brain of rats.
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DOI：
10.1016/j.taap.2016.02.004
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发表时间：
2016-05-15
影响因子：
3.8
通讯作者：
Kreyling WG
中科院分区：
文献类型：
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作者：
Kreyling WG
吸入纳米颗粒（NP）的生物动力学比大颗粒更复杂，因为NP可能沉积在上呼吸道（URT）的鼻粘膜上，可能转运到大脑嗅球，也可能通过三叉神经（URT神经元路线）转运；(b)沉积在下呼吸道（LRT）的NP可穿过ABB进入血液，并通过血脑屏障（BBB）进入大脑，或从神经衰弱的气管支气管上皮经迷走神经进入神经元途径。在健康成年大鼠雾化吸入20nm大小的192Ir放射性标记的铱NP 1小时后的前24小时内，通过不同暴露(I)仅鼻子暴露整个呼吸道或（II）气管内吸入插管和通气大鼠，从而绕过上呼吸道和胸外鼻道，量化上呼吸道和下呼吸道的易位。仅鼻子接触后的脑积累（BrAcc）明显比吸入IT后高9倍，因为前者来自两个途径（a + b），而后者仅来自途径(b)。有趣的是，仅鼻吸入24小时后血液中循环NP明显多于吸入IT后。根据不同的吸入暴露来区分上呼吸道易位和下呼吸道易位，前者明显高于下呼吸道易位（8倍）。尽管与短期暴露后的NP总沉积相比，BrAcc分数相当低，但本研究证明，吸入的不溶性NP可以通过上呼吸道和下呼吸道在大脑中积累，这可能在慢性暴露期间触发和/或调节中枢神经系统（CNS）的不良健康影响。
The biokinetics of inhaled nanoparticles (NP) is more complex than that of larger particles since NP may NP deposited on the nasal mucosa of the upper respiratory tract (URT) may translocate to the olfactory bulb of the brain and also via the trigeminus (URT neuronal route); and (b) NP deposited in the lower respiratory tract (LRT) may cross the ABB into blood and enter the brain across the blood-brain-barrier (BBB) or take a neuronal route from enervated tracheo-bronchial epithelia via the vagus nerve. Translocation from both - the URT and the LRT - are quantified during the first 24 h after a 1-hour aerosol inhalation of 20 nm-sized, 192Ir radiolabeled iridium NP by healthy adult rats using differential exposures: (I) nose-only exposure of the entire respiratory tract or (II) intratracheal (IT) inhalation of intubated and ventilated rats, thereby bypassing the URT and extrathoracic nasal passages. After nose-only exposure brain accumulation (BrAcc) is significantly nine-fold higher than after IT inhalation since the former results from both pathways (a + b) while the latter exposure comes only from pathway (b). Interestingly, there are significantly more circulating NP in blood 24 h after nose-only inhalation than after IT inhalation. Distinguishing translocation from URT versus LRT estimated from the differential inhalation exposures, the former is significantly higher (8-fold) than from the LRT. Although the BrAcc fraction is rather low compared to total NP deposition after this short-term exposure, this study proofs that inhaled insoluble NP can accumulate in the brain from both – URT and LRT which may trigger and/or modulate adverse health effects in the central nervous system (CNS) during chronic exposure.