King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia.
King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia.
Toxicol In Vitro. 2019 Jun;57:18-27. doi: 10.1016/j.tiv.2019.02.004. Epub 2019 Feb 6.
Wide application of TiO nanoparticles (nTiO) and ubiquitous lead (Pb) pollution in natural environment enhance the chance of co-exposure of humans to Pb and nTiO. We investigated the effects of nTiO on Pb-induced toxicity in human lung epithelial (A549) cells. Results showed that nTiO was not toxic to A549 cells. Conversely, Pb-induced cytotoxicity and oxidative stress in A549 cells were evidenced by cell viability reduction, cell membrane damage, reactive oxygen species generation and depletion of antioxidants. The Pb was also found to alter the regulation of apoptotic genes and cell cycle. Interestingly, in co-exposure group (nTiO + Pb), nTiO effectively attenuated the cytotoxicity, oxidative stress and apoptotic responses of Pb in A549 cells. Cellular uptake experiments demonstrated that nTiO increased the bioaccumulation of Pb in cells. However, due to strong adsorption of Pb on nTiO, free Pb ions were not available even inside the cells. Hence, nTiO significantly prevented the bioavailability and toxicity of Pb in A549 cells. This is the first report providing insight into understanding the mechanism of nTiO mediated prevention against Pb-induced toxicity in human cells. This study warranted further research on co-exposure effects of nTiO and Pb at in vivo mammalian models.
纳米 TiO 颗粒（nTiO）的广泛应用和环境中普遍存在的铅（Pb）污染增加了人类同时接触 Pb 和 nTiO 的可能性。我们研究了 nTiO 对人肺上皮（A549）细胞中 Pb 诱导毒性的影响。结果表明，nTiO 对 A549 细胞没有毒性。相反，细胞活力降低、细胞膜损伤、活性氧生成和抗氧化剂耗竭表明 Pb 诱导了 A549 细胞的细胞毒性和氧化应激。还发现 Pb 改变了凋亡基因和细胞周期的调节。有趣的是，在共暴露组（nTiO+Pb）中，nTiO 有效减轻了 A549 细胞中 Pb 的细胞毒性、氧化应激和凋亡反应。细胞摄取实验表明，nTiO 增加了细胞内 Pb 的生物积累。然而，由于 Pb 强烈吸附在 nTiO 上，即使在细胞内也没有游离的 Pb 离子。因此，nTiO 显著防止了 Pb 在 A549 细胞中的生物利用度和毒性。这是首次报道揭示了 nTiO 介导的预防人细胞中 Pb 诱导毒性的机制。这项研究需要在体内哺乳动物模型中进一步研究 nTiO 和 Pb 的共暴露效应。
