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气管内滴注潜在抗氧化药物聚乙二醇化纳米氧化铈后对大鼠肺毒性的评估。

Assessment of pulmonary toxicity of potential antioxidant drug PEGylated nanoceria after intratracheal instillation in rats.

作者信息

Qian Qinqing, Zhang Yun, Chen Yuan, Ye Chenqiao, Feng Qiang, Tu Jinqing, Lu Zhenbo, Xu Yilan, Ran Na, Xing Guiying, Yu Zhangsen

机构信息

Laboratory of Nanomedicine, Medical Science Research Center, School of Medicine, Shaoxing University, Shaoxing, China.

出版信息

J Appl Toxicol. 2021 Jun;41(6):941-952. doi: 10.1002/jat.4079. Epub 2020 Oct 22.

DOI:10.1002/jat.4079
PMID:33094530
Abstract

Cerium oxide (CeO ) nanoparticles have unique redox properties and exert excellent antioxidant effects in the biological environment. In recent years, many researchers have focused on the CeO nanoparticles as an effective antioxidant drug in the prevention and treatment of various diseases. However, the toxicity of CeO 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 CeO 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.

摘要

氧化铈(CeO)纳米颗粒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,许多研究人员将氧化铈纳米颗粒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,氧化铈纳米颗粒在体内的毒性仍存在争议,仍需深入研究。因此,本研究的目的是通过单次气管内滴注(IT),研究大鼠在暴露于聚乙二醇化氧化铈纳米颗粒(简称为CNPs;暴露剂量为2、10或20 mg/kg)14天后的肺部和全身毒性。我们评估了肺损伤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检查显示,20 mg/kg实验组大鼠出现了轻微的肺部炎症。然而,各组大鼠肺组织中的炎症因子并未显著增加,实验组肺组织匀浆中的超氧化物歧化酶(SOD)和谷胱甘肽(GSH)水平显著升高。总体而言,这些结果表明,高剂量的CNPs经肺部暴露可诱发轻度肺部炎症,但不会导致严重的全身毒性。此外,我们推测CNPs对大鼠肺部毒性的机制是内质网应激介导的健康肺上皮细胞自噬死亡。我们的结果表明,CNPs可安全地用作治疗氧化应激性肺部疾病的抗氧化药物。

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