Kubátová Alena, Dronen Laura C, Picklo Matthew J, Hawthorne Steven B
Energy & Environmental Research Center, P.O. Box 9018, University of North Dakota, Grand Forks, North Dakota 58202-9018, USA.
Chem Res Toxicol. 2006 Feb;19(2):255-61. doi: 10.1021/tx050172f.
Wood smoke particulate matter (PM) is a complex mixture of components falling in a spectrum of highly polar to nonpolar species. Wood smoke PM is a likely factor in pulmonary disease and induces oxidative damage. Most toxicity studies focus upon nonpolar species such as polycyclic aromatic hydrocarbons (PAHs). However, the role of more polar PM constituents as toxicants is not clear. In this work, we evaluated the ability of multiple fractions of varying polarity to deplete glutathione (GSH) in RAW 264.7 macrophages and BEAS-2B bronchial epithelial cells. We utilized hot pressurized (subcritical) water to fractionate wood smoke PM into seven fractions of decreasing polarity. In contrast to polar fractions, midpolarity and nonpolar fractions exhibited greater GSH depletion (ED50 at PM concentrations of approximately 50 microg/mL). GSH depletion caused by nonpolar fractions (extracted at 250-300 degrees C) was associated with the presence of PAHs. In midpolarity fractions (extracted at 100-150 degrees C), oxy-PAHs, syringylguaiacyls, disyringyls, and lower molecular weight PAHs were found. Direct comparison of GSH depletion by individual oxy-PAHs and PAHs suggests that oxy-PAHs are contributors to oxidative stress caused by wood smoke PM. However, other unidentified PM constituents contribute to GSH depletion as well. The results indicate the toxicological importance of oxygenated organics found in midpolarity PM fractions.
木烟颗粒物(PM)是一种成分复杂的混合物,包含从高极性到非极性的一系列物质。木烟PM可能是导致肺部疾病的一个因素,并会引发氧化损伤。大多数毒性研究集中在非极性物质上,如多环芳烃(PAHs)。然而,极性更强的PM成分作为有毒物质的作用尚不清楚。在这项研究中,我们评估了不同极性的多个组分在RAW 264.7巨噬细胞和BEAS - 2B支气管上皮细胞中消耗谷胱甘肽(GSH)的能力。我们利用热压(亚临界)水将木烟PM分离成七个极性逐渐降低的组分。与极性组分相比,中极性和非极性组分表现出更强的GSH消耗能力(在PM浓度约为50μg/mL时的半数有效剂量)。非极性组分(在250 - 300摄氏度下提取)导致的GSH消耗与PAHs的存在有关。在中极性组分(在100 - 150摄氏度下提取)中,发现了含氧多环芳烃、丁香基愈创木酚、二丁香基化合物和低分子量的PAHs。对单个含氧多环芳烃和PAHs消耗GSH能力的直接比较表明,含氧多环芳烃是木烟PM引起氧化应激的原因之一。然而,其他未鉴定的PM成分也会导致GSH的消耗。结果表明了中极性PM组分中含氧有机物的毒理学重要性。