Hiyoshi Takako, Nishime Chiyoko, Nishinaka Eiko, Seki Fumiko, Kawai Kenji, Mochizuki Misa, Urano Koji, Imai Toshio, Yamamoto Taichi, Suzuki Masami
Translational Research Division, Central Institute for Experimental Medical and Life Science, 25-12-3 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan.
CLEA Japan Inc., 4839-23 Kitayama, Fujinomiya, Shizuoka 418-0112, Japan.
J Toxicol Pathol. 2024 Apr;37(2):93-97. doi: 10.1293/tox.2023-0123. Epub 2024 Feb 23.
This study aimed to establish an exposure method that can induce homogeneous lesions with minimal inter-individual variability. The distribution of lesions induced by bleomycin (BLM) administration was also analyzed. C57BL mice were intrabronchially administered 20 µL of BLM (3 mg/mL) using a bronchoscope in the left or right bronchus. The mice were sacrificed 14 days after administration, and their lungs were evaluated histopathologically. BLM-induced inflammatory lesions were widely observed in the lungs. In the left bronchus-treated group, lesions were uniformly observed throughout the lobe, and no individual differences were noted. Meanwhile, in the right bronchus-treated group, individual differences in the distribution of the pulmonary lesions were observed. The distribution of lesions differed among the four lobes of the right lung owing to their anatomical features. Administration into the left bronchus is recommended for highly homogeneous lung exposure and for establishing models that contribute to highly accurate toxicity and efficacy evaluations.
本研究旨在建立一种能诱导出具有最小个体间变异性的均匀病变的暴露方法。还分析了博来霉素(BLM)给药诱导的病变分布情况。使用支气管镜在C57BL小鼠的左或右支气管内给予20 μL的BLM(3 mg/mL)。给药14天后处死小鼠,并对其肺进行组织病理学评估。在肺中广泛观察到BLM诱导的炎性病变。在左支气管治疗组中,整个肺叶均观察到均匀的病变,未发现个体差异。同时,在右支气管治疗组中,观察到肺部病变分布存在个体差异。由于右肺四个肺叶的解剖特征,病变分布有所不同。建议将药物注入左支气管,以实现高度均匀的肺部暴露,并建立有助于进行高度准确的毒性和疗效评估的模型。