Radcliffe Pheona M, Olabisi Ayodele O, Wagner Dean J, Leavens Teresa, Wong Brian A, Struve Melanie F, Chapman Gail D, Wilfong Erin R, Dorman David C
Colgate-Palmolive Company, Piscataway, NJ, United States.
Neurotoxicology. 2009 May;30(3):445-50. doi: 10.1016/j.neuro.2009.02.004. Epub 2009 Feb 13.
Olfactory transport of represents an important mechanism for direct delivery of certain metals to the central nervous system (CNS). The objective of this study was to determine whether inhaled tungsten (W) undergoes olfactory uptake and transport to the rat brain. Male, 16-week-old, Sprague-Dawley rats underwent a single, 90-min, nose-only exposure to a Na(2)(188)WO(4) aerosol (256 mg W/m(3)). Rats had the right nostril plugged to prevent nasal deposition of (188)W on the occluded side. The left and right sides of the nose and brain, including the olfactory pathway and striatum, were sampled at 0, 1, 3, 7, and 21 days post-exposure. Gamma spectrometry (n=7 rats/time point) was used to compare the levels of (188)W found on the left and right sides of the nose and brain and blood to determine the contribution of olfactory uptake to brain (188)W levels. Respiratory and olfactory epithelial samples from the side with the occluded nostril had significantly lower end-of-exposure (188)W levels confirming the occlusion procedure. Olfactory bulb, olfactory tract/tubercle, striatum, cerebellum, rest of brain (188)W levels paralleled blood (188)W concentrations at approximately 2-3% of measured blood levels. Brain (188)W concentrations were highest immediately following exposure, and returned to near background concentrations within 3 days. A statistically significant difference in olfactory bulb (188)W concentration was seen at 3 days post-exposure. At this time, (188)W concentrations in the olfactory bulb from the side ipsilateral to the unoccluded nostril were approximately 4-fold higher than those seen in the contralateral olfactory bulb. Our data suggest that the concentration of (188)W in the olfactory bulb remained low throughout the experiment, i.e., approximately 1-3% of the amount of tungsten seen in the olfactory epithelium suggesting that olfactory transport plays a minimal role in delivering tungsten to the rat brain.
嗅觉传输是某些金属直接输送到中枢神经系统(CNS)的重要机制。本研究的目的是确定吸入的钨(W)是否通过嗅觉被摄取并运输到大鼠大脑。16周龄的雄性Sprague-Dawley大鼠接受了单次、持续90分钟的仅经鼻暴露于Na₂¹⁸⁸WO₄气雾剂(256毫克W/立方米)。大鼠右侧鼻孔被堵塞,以防止¹⁸⁸W在堵塞侧鼻腔沉积。在暴露后0、1、3、7和21天对鼻子和大脑的左右两侧,包括嗅觉通路和纹状体进行取样。使用γ能谱法(每个时间点n = 7只大鼠)比较在鼻子、大脑和血液左右两侧发现的¹⁸⁸W水平,以确定嗅觉摄取对大脑¹⁸⁸W水平的贡献。堵塞鼻孔一侧的呼吸和嗅觉上皮样本在暴露结束时的¹⁸⁸W水平显著较低,证实了堵塞程序。嗅球、嗅束/结节、纹状体、小脑、大脑其他部位的¹⁸⁸W水平与血液¹⁸⁸W浓度平行,约为测量血液水平的2 - 3%。大脑¹⁸⁸W浓度在暴露后立即最高,并在3天内恢复到接近背景浓度。在暴露后3天,嗅球¹⁸⁸W浓度存在统计学上的显著差异。此时,未堵塞鼻孔同侧嗅球中的¹⁸⁸W浓度比另一侧嗅球中的约高4倍。我们的数据表明,在整个实验过程中,嗅球中¹⁸⁸W的浓度一直很低,即约为嗅觉上皮中钨含量的1 - 3%,这表明嗅觉传输在将钨输送到大鼠大脑中起的作用很小。