Background

Although polyhexamethylene guanidine phosphate (PHMG) is the main antibacterial ingredient in humidifier disinfectants, inhalation of PHMG causes severe respiratory diseases, including pulmonary fibrosis and asthma. Many studies using animal models have been conducted to investigate the molecular mechanisms of PHMG-induced pulmonary diseases. However, there have been no comparative studies analyzing the differences in sensitivity according to different strains, especially in rats.

Objective

In this study, we investigated pulmonary toxicity by comparing the pathological features in various strains of PHMG-instilled rats including Fischer 344 (F344), Sprague Dawley (SD), and Wistar rats.

Results

During the experimental periods, mortality rates of 1 and 2 mg/kg PHMG-instilled F344 rats and 2 mg/kg PHMG-instilled SD rats were 16.7%, 33.3%, and 33% respectively. However, there were no deaths in PHMG-instilled Wistar rats. Body weight significantly decreased in all rat strains immediately after the first PHMG instillation, and gradually recovered again after Day 5. Absolute and relative lung weights in all rat strains significantly increased after dose-dependent PHMG instillation. Histopathological analysis of all PHMG-instilled rat strains showed clear granulomatous inflammation, interstitial inflammation, squamous cell metaplasia, and macrophage infiltration in the alveoli. Specifically, eosinophilic infiltration in the alveoli was only observed in PHMG-instilled SD and Wistar rats. In addition, immunohistochemistry assessment revealed the presence of TGF-β1-positive cells in the lung tissues of all PHMG-instilled rat strains, and IL-5-positive cells in the lung tissues of PHMG-instilled SD and Wistar rats.

Conclusion

These results could potentially provide baseline data on the selection of experimental species for inhalation toxicity studies.

中文翻译：

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聚六亚甲基磷酸胍对三株大鼠的毒性比较

背景

虽然聚六亚甲基磷酸胍 (PHMG) 是加湿器消毒剂中的主要抗菌成分，但吸入 PHMG 会导致严重的呼吸系统疾病，包括肺纤维化和哮喘。已经进行了许多使用动物模型的研究来研究 PHMG 诱导的肺部疾病的分子机制。然而，还没有比较研究分析不同品系的敏感性差异，特别是在大鼠中。

客观的

在这项研究中，我们通过比较不同品系 PHMG 灌注大鼠的病理特征来研究肺毒性，包括 Fischer 344 (F344)、Sprague Dawley (SD) 和 Wistar 大鼠。

结果

实验期间，灌输1和2 mg/kg PHMG的F344大鼠和灌输2 mg/kg PHMG的SD大鼠的死亡率分别为16.7%、33.3%和33%。然而，在灌输 PHMG 的 Wistar 大鼠中没有死亡。在第一次 PHMG 滴注后，所有大鼠品系的体重立即显着下降，并在第 5 天后逐渐恢复。所有大鼠品系的绝对和相对肺重量在剂量依赖性 PHMG 滴注后显着增加。所有 PHMG 灌输的大鼠品系的组织病理学分析显示，肺泡中有明显的肉芽肿性炎症、间质性炎症、鳞状细胞化生和巨噬细胞浸润。具体而言，仅在灌注 PHMG 的 SD 和 Wistar 大鼠中观察到肺泡中的嗜酸性粒细胞浸润。此外，

结论

这些结果可能为选择用于吸入毒性研究的实验物种提供基线数据。