Department of Environmental Health, Osaka Prefectural Institute of Public Health, Osaka, Japan.
Inhal Toxicol. 2010 Sep;22(11):930-6. doi: 10.3109/08958378.2010.496476.
Many epidemiological studies on the effects of nitrogen dioxide (NO(2)) on respiratory function may have included nitrous acid (HONO) exposures in their measures, because conventional NO(2) assays detect HONO as NO(2). A few epidemiological studies and human HONO inhalation experiments have associated HONO with decrements in lung functions. However, there have been few HONO exposure experiments in animals. This study aims to develop a HONO generation system for the animal exposure experiments, and to assess the association of HONO exposure with histopathologic alterations in the respiratory tract of guinea pigs. We exposed the guinea pigs to 3.6 ppm HONO with secondary products of 0.3 ppm NO(2) and 1.6 ppm nitric oxide (NO) for 4 weeks (24 h/day). We conducted histopathologic analyses and measured specific airway resistance (sRaw) from 7 h 40 min to 8 h 30 min after the end of HONO exposure. We found pulmonary emphysema-like alterations in the alveolar duct centriacinar regions, distortion of the centriacinar regions of alveolar ducts with extension of the bronchial epithelial cells and smooth muscle cells, and expansion of bronchial epithelial cells, in the HONO exposure. These histopathologic results suggest that a high concentration of HONO with some NO(2) and NO may associate with decrements in lung functions and some respiratory symptoms. Although the increased tendency of the sRaw value was observed in the HONO exposure group, no statistically significant difference was found between the sRaw values from the HONO exposure group and the filtered air group (p = 0.06, student's t-test).
许多关于二氧化氮（NO2）对呼吸功能影响的流行病学研究可能在其测量中包含了亚硝酸（HONO）暴露，因为常规的 NO2 检测会将 HONO 检测为 NO2。一些流行病学研究和人类 HONO 吸入实验已经将 HONO 与肺功能下降联系起来。然而，动物中 HONO 暴露实验较少。本研究旨在开发一种 HONO 发生系统，用于动物暴露实验，并评估 HONO 暴露与豚鼠呼吸道组织病理学改变的关系。我们将豚鼠暴露于 3.6 ppm 的 HONO 及其二次产物 0.3 ppm 的 NO2 和 1.6 ppm 的一氧化氮（NO）中 4 周（每天 24 小时）。我们进行了组织病理学分析，并在 HONO 暴露结束后 7 小时 40 分至 8 小时 30 分测量了特定气道阻力（sRaw）。我们发现，在 HONO 暴露组中，肺泡导管中心腺区域出现了肺气肿样改变，肺泡导管的中心腺区域变形，支气管上皮细胞和平滑肌细胞延伸，以及支气管上皮细胞扩张。这些组织病理学结果表明，高浓度的 HONO 与一些 NO2 和 NO 可能与肺功能下降和一些呼吸道症状有关。尽管在 HONO 暴露组中观察到 sRaw 值增加的趋势，但在 HONO 暴露组和过滤空气组之间的 sRaw 值没有发现统计学上的显著差异（p = 0.06，学生 t 检验）。
