Numano Takamasa, Morioka Mai, Higuchi Hitomi, Uda Kazunari, Sugiyama Taiki, Hagiwara Teruaki, Doi Yuko, Imai Norio, Kawabe Mayumi, Mera Yukinori, Tamano Seiko
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan.
J Toxicol Pathol. 2020 Jan;33(1):11-19. doi: 10.1293/tox.2019-0060. Epub 2019 Sep 28.
Intratracheal instillation is the introduction of a substance directly into the trachea. Intratracheal instillation has been used to investigate the lung toxicity of several chemicals and requires the suspension or dissolution of test material in a vehicle for even dispersal throughout the lung. Importantly, the toxicities of vehicles used in intratracheal instillation studies are generally considered to be insignificant. Hence, evaluating the influence of different vehicles on the lung due to intratracheal instillation is crucial. We examined the toxic effects of pure water, saline, phosphate buffered saline (PBS), 0.5% Kolliphor P188 (KP188), 0.1% Tween 20 in saline, and 1.0% BSA in PBS. These vehicles were administered to male Crl:CD(SD) rats by a single intratracheal instillation. On day 3, broncho-alveolar lavage fluid (BALF) from the right lung was collected and processed for cell counting and biochemical analysis, while the left lung was used for histopathological examination. Accumulation of alveolar macrophages was observed in all vehicle-treated groups but was minimal in the group administered saline, somewhat higher in the groups administered pure water, PBS, 0.1% Tween 20, and 1% BSA, and notably higher in the group administered 0.5% KP188. The results from BALF analysis indicated that intratracheal instillation of 0.5% KP188 also induced alveolar damage. Additionally, administering pure water did not appear to cause tissue damage. Eosinophil infiltration in the interstitial regions was histopathologically observed. Altogether, the results of this study are helpful for the selection of appropriate vehicles for use in intratracheal instillation studies.
气管内滴注是将一种物质直接引入气管。气管内滴注已被用于研究几种化学物质的肺毒性,并且需要将测试材料悬浮或溶解在载体中以便在整个肺部均匀分散。重要的是,气管内滴注研究中使用的载体的毒性通常被认为是微不足道的。因此,评估不同载体因气管内滴注对肺部的影响至关重要。我们研究了纯水、生理盐水、磷酸盐缓冲盐水(PBS)、0.5%聚氧乙烯蓖麻油(KP188)、0.1%吐温20的生理盐水溶液以及1.0% PBS中的牛血清白蛋白(BSA)的毒性作用。通过单次气管内滴注将这些载体给予雄性Crl:CD(SD)大鼠。在第3天,收集右肺的支气管肺泡灌洗液(BALF)并进行细胞计数和生化分析,而左肺用于组织病理学检查。在所有载体处理组中均观察到肺泡巨噬细胞的积聚,但在给予生理盐水的组中最少,在给予纯水、PBS、0.1%吐温20和1% BSA的组中略高,在给予0.5% KP188的组中显著更高。BALF分析结果表明,气管内滴注0.5% KP188也会诱导肺泡损伤。此外,给予纯水似乎不会引起组织损伤。组织病理学观察到间质区域有嗜酸性粒细胞浸润。总之,本研究结果有助于在气管内滴注研究中选择合适的载体。