Zhang Q, Kusaka Y, Sato K, Nakakuki K, Kohyama N, Donaldson K
Department of Environmental Health, Fukui Medical School, Japan.
J Toxicol Environ Health A. 1998 Mar 27;53(6):423-38. doi: 10.1080/009841098159169.
Nickel and cobalt, which belong to the same elemental group, are known to cause interstitial lung disease and bronchial asthma. The ability of these metals to injure lung cells and cause inflammation is likely to be important in their pathogenicity but comparative studies are rare. Additionally, ultrafine (uf) forms of these metals are used increasingly and there is little available information on their toxicity. Thus the inflammatory response following intratracheal instillation of ultrafine particles of Co, Ni, and TiO2 was compared. Physiological saline (PS) was used as a vehicle control and DQ12 quartz as a positive control. Male Wistar rats were intratracheally instilled with the 3 particle types at a dose of 1 mg suspended in physiological saline. At 1, 3, 7, 15, and 30 d after the injection, lung weight and the cellular and biochemical changes in bronchoalveolar lavage fluid (BALF) were determined. By all of the indices, Uf-Ni appeared to be the most injurious to the lung, causing severe and sustained inflammation, cytotoxicity and increased epithelial permeability. The next most toxic material was DQ12 quartz, with Uf-Co being closely similar in ability to cause inflammation. Uf-TiO2 was more active than the saline control in all of the indices, but was the least toxic of the particles studied. The present study reveals that three ultrafine particles of the same diameter are dramatically different in their ability to cause inflammation. The three ultrafines were compared as to their ability to cause free-radical damage to supercoiled plasmid DNA, and the result of free-radical activity was found to be Uf-TiO2 << Uf-Co = Uf-Ni. Difference in free-radical-generation activity therefore could underlie the difference in inflammation of these three ultrafine particle types.
镍和钴属于同一元素族，已知它们会引发间质性肺病和支气管哮喘。这些金属损伤肺细胞并引发炎症的能力在其致病性方面可能很重要，但相关的比较研究很少。此外，这些金属的超细（uf）形式的使用越来越多，而关于其毒性的可用信息却很少。因此，比较了气管内注入钴、镍和二氧化钛超细颗粒后的炎症反应。使用生理盐水（PS）作为溶剂对照，DQ12石英作为阳性对照。将雄性Wistar大鼠气管内注入以生理盐水悬浮的1毫克剂量的这三种颗粒类型。在注射后1、3、7、15和30天，测定肺重量以及支气管肺泡灌洗液（BALF）中的细胞和生化变化。根据所有指标，超细镍似乎对肺的损伤最大，会引发严重且持续的炎症、细胞毒性并增加上皮通透性。毒性次之的物质是DQ12石英，超细钴引发炎症的能力与之相近。超细二氧化钛在所有指标上都比生理盐水对照更活跃，但在所研究的颗粒中毒性最小。本研究表明，三种直径相同的超细颗粒引发炎症的能力差异巨大。比较了这三种超细颗粒对超螺旋质粒DNA造成自由基损伤的能力，发现自由基活性的结果是超细二氧化钛 << 超细钴 = 超细镍。因此，自由基生成活性的差异可能是这三种超细颗粒类型炎症差异的基础。
