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Assessment of pulmonary toxicity of potential antioxidant drug PEGylated nanoceria after intratracheal instillation in rats
Journal of Applied Toxicology ( IF 3.3 ) Pub Date : 2020-10-22 , DOI: 10.1002/jat.4079
Qinqing Qian 1 , Yun Zhang 1 , Yuan Chen 1 , Chenqiao Ye 1 , Qiang Feng 1 , Jinqing Tu 1 , Zhenbo Lu 1 , Yilan Xu 1 , Na Ran 1 , Guiying Xing 1 , Zhangsen Yu 1
Affiliation  

Cerium oxide (CeO2) nanoparticles have unique redox properties and exert excellent antioxidant effects in the biological environment. In recent years, many researchers have focused on the CeO2 nanoparticles as an effective antioxidant drug in the prevention and treatment of various diseases. However, the toxicity of CeO2 nanoparticles in vivo remains controversial and still needs intensive research. Therefore, the objective of this study is to investigate the pulmonary and systemic toxicity in rats after 14 days of exposure to the PEGylated CeO2 nanoparticles (abbreviated as CNPs; exposure dose of 2, 10, or 20 mg/kg) through a single intratracheal instillation (IT). We assessed the indicators of lung injury and the pathological damage degree of lung tissue. The bronchoalveolar lavage fluid (BALF) analysis and lung histopathology revealed the occurrence of slight pulmonary inflammation in the 20‐mg/kg experimental group rats. However, the inflammation factors in the lung tissue of every group rats did not significantly increase, and the levels of superoxide dismutase (SOD) and glutathione (GSH) in lung tissue homogenate rose considerably in the experimental groups. Collectively, these results indicated that pulmonary exposure by the high dose of CNPs could induce mild pulmonary inflammation but did not cause severe systemic toxicity. Moreover, we speculate that the mechanism of pulmonary toxicity of CNPs in rats was due to the autophagic death of healthy lung epithelial cells mediated by endoplasmic reticulum stress. Our results implicate that CNPs can be safely used as an antioxidant drug for the oxidative stress pulmonary diseases.

中文翻译:

大鼠气管内滴注后潜在抗氧化药物聚乙二醇化纳米纤维素的肺毒性评估

氧化铈 (CeO 2 ) 纳米粒子具有独特的氧化还原特性,并在生物环境中发挥出色的抗氧化作用。近年来,许多研究人员将CeO 2纳米粒子作为一种有效的抗氧化药物用于预防和治疗各种疾病。然而,CeO 2纳米粒子在体内的毒性仍存在争议,仍需深入研究。因此,本研究的目的是研究暴露于聚乙二醇化 CeO 2 14 天后大鼠的肺和全身毒性。纳米颗粒(缩写为 CNP;暴露剂量为 2、10 或 20 mg/kg)通过单次气管内滴注 (IT)。我们评估了肺损伤的指标和肺组织的病理损伤程度。支气管肺泡灌洗液 (BALF) 分析和肺组织病理学显示,20-mg/kg 实验组大鼠发生了轻微的肺部炎症。但各组大鼠肺组织炎症因子均无明显升高,实验组肺组织匀浆中超氧化物歧化酶(SOD)和谷胱甘肽(GSH)含量明显升高。总的来说,这些结果表明,高剂量 CNP 的肺部暴露可引起轻度肺部炎症,但不会引起严重的全身毒性。而且,我们推测CNPs对大鼠肺毒性的机制是由于内质网应激介导的健康肺上皮细胞的自噬性死亡。我们的结果表明,CNPs 可以安全地用作氧化应激肺病的抗氧化药物。
更新日期:2020-10-22
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