Kanie Shohei, Yokohira Masanao, Yamakawa Keiko, Nakano-Narusawa Yuko, Yoshida Shota, Hashimoto Nozomi, Imaida Katsumi
Onco-Pathology, Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Toxicology Laboratory, Discovery and Preclinical Research Division, TAIHO Pharmaceutical Co., Ltd., 224-2 Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan.
J Toxicol Pathol. 2017 Apr;30(2):153-159. doi: 10.1293/tox.2016-0050. Epub 2016 Dec 22.
Surfactant proteins (SPs) are essential to respiratory structure and function. The expectorant drug ambroxol hydrochloride is clinically prescribed to stimulate pulmonary surfactant and airway serous secretion. Therefore, ambroxol hydrochloride may affect SP production and pulmonary inflammation. Lung toxicity of fine particles of various materials has been examined previously in our bioassay using the intratracheal (i.t.) instillation approach. In the present study, we evaluated modulatory effects of ambroxol hydrochloride on quartz-induced lung inflammation in F344 rats. Male 6-week-old F344 rats were exposed by i.t. instillation to 2 mg of quartz particles suspended in 0.2 mL of saline. Ambroxol hydrochloride was administered at 0, 12, and 120 ppm in rat basal diet for 28 days, and then formalin-fixed paraffin-embedded lung, liver, and kidney samples were prepared. No changes in general condition, body and organ weights, or food consumption upon exposure to quartz were noted. The mean ambroxol intake in rats of the 12 ppm group was comparable to the human conventional dose. Histopathology of lung lesions was evaluated, and the degree of inflammation was scored. At 120 ppm, ambroxol hydrochloride significantly decreased individual lung inflammation scores for pulmonary edema and lymph follicle proliferation around the bronchiole, as well as the total inflammation score, in quartz-treated rats. Expression of SP-C in the type II alveolar cells and macrophages was greater in inflammatory lesions than in non-inflamed areas. Ambroxol treatment did not affect expression of SP-B and SP-C. In conclusion, we demonstrated that ambroxol hydrochloride relieves quartz-induced lung inflammation.
表面活性蛋白（SPs）对呼吸结构和功能至关重要。临床开具祛痰药物盐酸氨溴索以刺激肺表面活性物质和气道浆液分泌。因此，盐酸氨溴索可能会影响SP的产生和肺部炎症。此前我们已使用气管内（i.t.）滴注法在生物测定中检测了各种材料细颗粒的肺毒性。在本研究中，我们评估了盐酸氨溴索对石英诱导的F344大鼠肺部炎症的调节作用。6周龄雄性F344大鼠通过气管内滴注暴露于悬浮在0.2 mL盐水中的2 mg石英颗粒。盐酸氨溴索以0、12和120 ppm的浓度添加到大鼠基础饮食中，持续28天，然后制备福尔马林固定石蜡包埋的肺、肝和肾样本。暴露于石英后，未观察到大鼠的一般状况、体重和器官重量或食物摄入量有变化。12 ppm组大鼠的平均氨溴索摄入量与人类常规剂量相当。对肺部病变进行组织病理学评估，并对炎症程度进行评分。在120 ppm时，盐酸氨溴索显著降低了石英处理大鼠的肺水肿和细支气管周围淋巴滤泡增殖的个体肺部炎症评分以及总炎症评分。炎症病变中II型肺泡细胞和巨噬细胞中SP-C的表达高于非炎症区域。氨溴索治疗不影响SP-B和SP-C的表达。总之，我们证明了盐酸氨溴索可减轻石英诱导的肺部炎症。
