纳米氧化亚铜和氧化铜的肺细胞毒性差异及影响因素
Different Pulmonary Cytotoxicity of Nano-cuprous Oxide and Nano-copper Oxide and Influencing Factors
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摘要: 纳米农药的广泛应用将不可避免导致其重要成分(比如纳米氧化铜和纳米氧化亚铜)的环境残留。人体可通过灰尘吸入、饮水及农产品摄入等方式暴露于纳米氧化铜和纳米氧化亚铜。因此,阐明它们的健康危害具有重要意义。本研究我们首次对比研究了纳米氧化铜和纳米氧化亚铜的A549肺细胞毒性差异,并从氧化应激和线粒体损伤角度探讨了细胞毒性作用机制。实验结果表明纳米氧化铜和纳米氧化亚铜均具有显著的A549细胞毒性,观察到的最低效应浓度分别为20 mg·L-1和5 mg·L-1。纳米氧化亚铜表现出更强的细胞毒性作用,100 mg·L-1时细胞活性抑制率达到95%。活性氧实验结果表明纳米氧化铜和纳米氧化亚铜均可诱导活性氧生成,呈现时间与浓度依赖关系。纳米氧化亚铜的活性氧诱导作用明显强于纳米氧化铜,24 h最大诱导率分别为对照组的3.5倍和1.5倍。线粒体膜电位实验结果表明纳米氧化亚铜比纳米氧化铜具有更强的线粒体去极化作用,并呈剂量(1~100 mg·L-1)依赖关系,最大线粒体膜电位下降率分别为60%和20%。活性氧和线粒体膜电位的结果与细胞毒性的结果基本一致,提示了氧化应激和线粒体损伤可能是导致纳米氧化铜和纳米氧化亚铜细胞毒性的关键分子机制。本研究揭示了纳米氧化铜和纳米氧化亚铜的肺细胞毒性差异及潜在分子机制,可为纳米农药的健康风险评估及合理施用提供重要理论依据。Abstract: The wide application of nano-pesticides leads to residues of its main components (such as nano-copper oxide and nano-cuprous oxide) in the environment inevitably. The human body can expose to nano-copper oxide and nano-cuprous oxide through inhaling dust, drinking water and ingesting agricultural products. Therefore, it is of great significance to elucidate their health hazards. In the present study, we firstly investigated the cytotoxicity variation of nano-copper oxide and nano-cuprous oxide on A549 cells as well as explored the cytotoxic mechanisms from the perspectives of oxidative stress and mitochondrial damage. Results showed that both nano-copper oxide and nano-cuprous oxide had significant cytotoxic effects on A549 cells, with the lowest observed effective concentrations of 20 mg·L-1 and 5 mg·L-1, respectively. Nano-cuprous oxide exhibited stronger cytotoxic effects than nano-copper oxide with inhibition rate of cell viability reaching 95% at 100 mg·L-1. The experimental results of reactive oxygen species showed that both nano-copper oxide and nano-cuprous oxide could induce the generation of reactive oxygen species in a time-dependent and concentration-dependent manner. The induction effect of nano-cuprous oxide on reactive oxygen species was significantly stronger than that of nano-copper oxide, with the maximum induction rate of 3.5-fold and 1.5-fold compared to the ctrl group at 24 h. The experimental results of mitochondrial membrane potential showed that nano-cuprous oxide had stronger activity on mitochondrial depolarization than nano-copper oxide in a dose-dependent manner (1~100 mg·L-1), with the maximum reduction rates of mitochondrial membrane potential reaching 60% and 20%, respectively. The results of reactive oxygen species and mitochondrial membrane potential were consistent with the results of cytotoxicity, indicating that oxidative stress and mitochondrial damage might be the key molecular mechanisms of cytotoxicity of nano-copper oxide and nano-cuprous oxide. This study revealed the different pulmonary cytotoxicity of nano-copper oxide and nano-cuprous oxide as well as the potential molecular mechanisms, which can provide important theoretical basis for the health risk assessment and rational application of nano-pesticides.
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Key words:
- nano-copper oxide /
- nano-cuprous oxide /
- lung cell /
- cytotoxicity /
- oxidative stress /
- mitochondria damage
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Li L, Xu Z L, Kah M, et al. Nanopesticides:A comprehensive assessment of environmental risk is needed before widespread agricultural application[J]. Environmental Science & Technology, 2019, 53(14):7923-7924 Usman M, Farooq M, Wakeel A, et al. Nanotechnology in agriculture:Current status, challenges and future opportunities[J]. The Science of the Total Environment, 2020, 721:137778 Kumar S, Nehra M, Dilbaghi N, et al. Nano-based smart pesticide formulations:Emerging opportunities for agriculture[J]. Journal of Controlled Release:Official Journal of the Controlled Release Society, 2019, 294:131-153 谢婷, 谭辉. 无机铜氧化物在农药领域的应用专利技术综述[J]. 科技创新与应用, 2019(19):23-24 陈朗, 姜辉, 周艳明, 等. 纳米农药的环境安全性浅析[J]. 农药科学与管理, 2018, 39(5):30-38 Chen L, Jiang H, Zhou Y M, et al. A brief analysis on the environmental safety of nano-enabled pesticides[J]. Pesticide Science and Administration, 2018, 39(5):30-38(in Chinese)
范文宏, 刘通, 史志伟, 等. 立方体和八面体微/纳米氧化亚铜对大型水蚤(Daphnia magna)的氧化胁迫和生理损伤[J]. 生态毒理学报, 2016, 11(5):40-48 Fan W H, Liu T, Shi Z W, et al. Oxidative stress and physiological damage of cubic and octahedral Cu2O micro/nanocrystals to Daphnia magna[J]. Asian Journal of Ecotoxicology, 2016, 11(5):40-48(in Chinese)
Gurianov Y, Nakonechny F, Albo Y, et al. Antibacterial composites of cuprous oxide nanoparticles and polyethylene[J]. International Journal of Molecular Sciences, 2019, 20(2):439 Rodríguez-Llamazares S, Mondaca M A, Badilla C, et al. PVC/copper oxide composites and their effect on bacterial adherence[J]. Journal of the Chilean Chemical Society, 2012, 57(2):1163-1165 Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology:An emerging discipline evolving from studies of ultrafine particles[J]. Environmental Health Perspectives, 2005, 113(7):823-839 Weichenthal S, Dufresne A, Infante-Rivard C. Indoor ultrafine particles and childhood asthma:Exploring a potential public health concern[J]. Indoor Air, 2007, 17(2):81-91 Jain A, Ranjan S, Dasgupta N, et al. Nanomaterials in food and agriculture:An overview on their safety concerns and regulatory issues[J]. Critical Reviews in Food Science and Nutrition, 2018, 58(2):297-317 Manke A, Wang L Y, Rojanasakul Y. Mechanisms of nanoparticle-induced oxidative stress and toxicity[J]. BioMed Research International, 2013, 2013:942916 Bhabra G, Sood A, Fisher B, et al. Nanoparticles can cause DNA damage across a cellular barrier[J]. Nature Nanotechnology, 2009, 4(12):876-883 孙婷婷, 蒋澄宇. 纳米氧化铜导致小鼠急性肺损伤[J]. 基础医学与临床, 2012, 32(4):386-389 Sun T T, Jiang C Y. Copper oxide nanoparticles induce acute pulmonary injury in mice[J]. Basic & Clinical Medicine, 2012, 32(4):386-389(in Chinese)
Fahmy B, Cormier S A. Copper oxide nanoparticles induce oxidative stress and cytotoxicity in airway epithelial cells[J]. Toxicology in Vitro, 2009, 23(7):1365-1371 Fu X. Oxidative stress induced by CuO nanoparticles (CuO NPs) to human hepatocarcinoma (HepG2) cells[J]. Journal of Cancer Therapy, 2015, 6(10):889-895 Zhao L J, Ortiz C, Adeleye A S, et al. Metabolomics to detect response of lettuce (Lactuca sativa) to Cu(OH)2 nanopesticides:Oxidative stress response and detoxification mechanisms[J]. Environmental Science & Technology, 2016, 50(17):9697-9707 王淑玲, 张玉喜, 刘汉柱, 等. 氧化铜纳米颗粒对水稻幼苗根系代谢毒性的研究[J]. 环境科学, 2014, 35(5):1968-1973 Wang S L, Zhang Y X, Liu H Z, et al. Phytotoxicity of copper oxide nanoparticles to metabolic activity in the roots of rice[J]. Environmental Science, 2014, 35(5):1968-1973(in Chinese)
Vignardi C P, Muller E B, Tran K, et al. Conventional and nano-copper pesticides are equally toxic to the estuarine amphipod Leptocheirus plumulosus[J]. Aquatic Toxicology, 2020, 224:105481 Zhang X X, Xu Z L, Qian X T, et al. Assessing the impacts of Cu(OH)2 nanopesticide and ionic copper on the soil enzyme activity and bacterial community[J]. Journal of Agricultural and Food Chemistry, 2020, 68(11):3372-3381 Carley L N, Panchagavi R, Song X, et al. Long-term effects of copper nanopesticides on soil and sediment community diversity in two outdoor mesocosm experiments[J]. Environmental Science & Technology, 2020, 54(14):8878-8889 Sengul A B, Asmatulu E. Toxicity of metal and metal oxide nanoparticles:A review[J]. Environmental Chemistry Letters, 2020, 18(5):1659-1683 García-Torra V, Cano A, Espina M, et al. State of the art on toxicological mechanisms of metal and metal oxide nanoparticles and strategies to reduce toxicological risks[J]. Toxics, 2021, 9(8):195 Manzanares D, Ceña V. Endocytosis:The nanoparticle and submicron nanocompounds gateway into the cell[J]. Pharmaceutics, 2020, 12(4):371 -
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