Wallenborn J Grace, McGee John K, Schladweiler Mette C, Ledbetter Allen D, Kodavanti Urmila P
Department of Environmental Sciences and Engineering, UNC School of Public Health, Chapel Hill, North Carolina 27599, USA.
Toxicol Sci. 2007 Jul;98(1):231-9. doi: 10.1093/toxsci/kfm088. Epub 2007 Apr 13.
Respirable ambient particulate matter (PM) exposure has been associated with an increased risk of cardiovascular disease. Direct translocation of PM-associated metals from the lungs into systemic circulation may be partly responsible. We measured elemental content of lungs, plasma, heart, and liver of healthy male WKY rats (12-15 weeks old) 4 or 24 h following a single intratracheal (IT) instillation of saline or 8.33 mg/kg of oil combustion PM (HP-12) containing a variety of transition metals with differing water and acid solubility. Tissues were digested with a combination of quaternary acid, amine, and nitric acid and analyzed using inductively coupled plasma-atomic emission spectroscopy. Lung levels of metals were lower at 24 h than at 4 h. Metals with high water solubility and relatively high concentration in HP-12 were increased in extrapulmonary organs. Water-soluble nonessential metals, like vanadium and nickel, were increased in plasma, hearts, and livers of exposed animals at both time points. Exposure-related small increases in essential metals, like zinc and manganese, were also noted in extrapulmonary tissues at both time points. Lead, with low water solubility but high acid solubility, was detected in liver only at 24-h postinstillation. Elements with low water or acid solubility, like silicon and aluminum, were not detected in extrapulmonary tissues despite decreased levels in the lung suggesting mucociliary clearance. We have shown that HP-12-associated metals translocate to systemic circulation and extrapulmonary organs following IT exposure. This translocation is dependent upon their relative levels and water solubility. Thus, following inhalation, PM-associated metals deposited in the lung may be released into systemic circulation at different rates depending on their water/acid solubility, thereby providing a means by which metals may elicit direct extrapulmonary effects.
可吸入环境颗粒物(PM)暴露与心血管疾病风险增加有关。PM相关金属从肺直接转移到体循环中可能是部分原因。我们在健康雄性WKY大鼠(12 - 15周龄)经气管内(IT)单次注入生理盐水或8.33 mg/kg含多种具有不同水和酸溶解度的过渡金属的油燃烧PM(HP - 12)后4小时或24小时,测量了肺、血浆、心脏和肝脏的元素含量。组织用季铵酸、胺和硝酸混合消化,并使用电感耦合等离子体原子发射光谱法进行分析。肺中金属水平在24小时时低于4小时。肺外器官中具有高水溶性且在HP - 12中浓度相对较高的金属增加。在两个时间点,暴露动物的血浆、心脏和肝脏中水溶性非必需金属如钒和镍都增加。在两个时间点的肺外组织中也注意到与暴露相关必需金属如锌和锰的小幅增加。铅水溶性低但酸溶性高,仅在注入后24小时在肝脏中检测到。尽管肺中水平降低表明有黏液纤毛清除作用,但在肺外组织中未检测到水或酸溶解度低的元素如硅和铝。我们已经表明,IT暴露后,HP - 12相关金属转移到体循环和肺外器官。这种转移取决于它们的相对水平和水溶性。因此,吸入后,沉积在肺中的PM相关金属可能根据其水/酸溶解度以不同速率释放到体循环中,从而提供了一种金属可能引发肺外直接作用的方式。