Abudayyak Mahmoud, Guzel Elif, Özhan Gül
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey.
Adv Pharm Bull. 2020 Jun;10(2):213-220. doi: 10.34172/apb.2020.025. Epub 2020 Feb 18.
The wide application of cupric oxide nanoparticles (copper (II) oxide, CuO-NPs) in various fields has increased exposure to the kind of active nanomaterials, which can cause negative effects on human and environment health. Although CuO-NPs were reported to be harmful to human, there is still a lack information related to their toxic potentials. In the present study, the toxic potentials of CuO-NPs were evaluated in the liver (HepG2 hepatocarcinoma) and intestine (Caco-2 colorectal adenocarcinoma) cells. After the characterization of particles, cellular uptake and morphological changes were determined. The potential of cytotoxic, genotoxic, oxidative and apoptotic damage was investigated with several assays. The average size of the nanoparticles was 34.9 nm, about 2%-5% of the exposure dose was detected in the cells and mainly accumulated in different organelles, causing oxidative stress, cell damages, and death. The IC50 values were 10.90 and 10.04 µg/mL by MTT assay, and 12.19 and 12.06 µg/mL by neutral red uptake (NRU) assay, in HepG2 and Caco-2 cells respectively. Apoptosis assumes to the main cell death pathway; the apoptosis percentages were 52.9% in HepG2 and 45.5% in Caco-2 cells. Comet assay result shows that the highest exposure concentration (20 µg/mL) causes tail intensities about 9.6 and 41.8%, in HepG2 and Caco-2 cells, respectively. CuO-NPs were found to cause significant cytotoxicity, genotoxicity, and oxidative and apoptotic effects in both cell lines. Indeed, CuO-NPs could be dangerous to human health even if their toxic mechanisms should be elucidated with further studies.
氧化铜纳米颗粒（氧化铜（II），CuO-NPs）在各个领域的广泛应用增加了人们对这类活性纳米材料的接触，而它们可能会对人类和环境健康产生负面影响。尽管有报道称CuO-NPs对人类有害，但仍缺乏有关其潜在毒性的信息。在本研究中，对CuO-NPs在肝脏（HepG2肝癌）和肠道（Caco-2结肠腺癌）细胞中的潜在毒性进行了评估。在对颗粒进行表征后，测定了细胞摄取和形态变化。通过多种检测方法研究了细胞毒性、遗传毒性、氧化和凋亡损伤的可能性。纳米颗粒的平均尺寸为34.9nm，在细胞中检测到约2%-5%的暴露剂量，且主要积聚在不同的细胞器中，从而导致氧化应激、细胞损伤和死亡。通过MTT法测定，HepG2和Caco-2细胞的IC50值分别为10.90和10.04μg/mL；通过中性红摄取（NRU）法测定，IC50值分别为12.19和12.06μg/mL。凋亡被认为是主要的细胞死亡途径；HepG2细胞和Caco-2细胞的凋亡率分别为52.9%和45.5%。彗星试验结果表明，最高暴露浓度（20μg/mL）在HepG2和Caco-2细胞中分别导致约9.6%和41.8%的尾部强度。发现CuO-NPs在两种细胞系中均会引起显著的细胞毒性、遗传毒性以及氧化和凋亡效应。事实上，即使其毒性机制有待进一步研究阐明，CuO-NPs对人类健康也可能是危险的。
