King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia.
King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia.
Chemosphere. 2019 Feb;216:823-831. doi: 10.1016/j.chemosphere.2018.10.214. Epub 2018 Oct 31.
Bismuth oxide nanoparticles (BiO NPs) have shown great potential for several applications including cosmetics and biomedicine. However, there is paucity of research on toxicity of BiO NPs. In this study, we first examined dose-dependent cytotoxicity and apoptosis response of BiO NPs in human breast cancer (MCF-7) cells. We further explored the potential mechanisms of cytotoxicity of BiO NPs through oxidative stress. Physicochemical study demonstrated that BiO NPs have crystalline structure and spherical shape with mean size of 97 nm. Toxicity studies have shown that BiO NPs reduce cell viability and induce membrane damage dose-dependently in the concentration range of 50-300 μg/ml. BiO NPs also disturbed cell cycle of MCF-7 cells. Oxidative stress response of BiO NPs was evident by generation of reactive oxygen species (ROS), higher lipid peroxidation, reduction of glutathione (GSH) and low superoxide dismutase (SOD) enzyme activity. Interestingly, supplementation of external antioxidant N-acetyl-cysteine almost negated the effect of BiO NPs induced oxidative stress and cell death. We also found that exposure of BiO NPs induced apoptotic response in MCF-7 cells suggested by impaired regulation of Bcl-2, Bax and caspase-3 genes. Altogether, we found that BiO NPs induced cytotoxicity in MCF-7 cells through modulating the redox homeostasis via Bax/Bcl-2 pathway. This study warranted further research to delineate the underlying mechanism of BiO NPs induced toxicity at in vivo level.
氧化铋纳米粒子（BiO NPs）在化妆品和生物医药等多个领域具有巨大的应用潜力。然而，目前关于 BiO NPs 的毒性研究还很少。在本研究中，我们首先研究了 BiO NPs 对人乳腺癌（MCF-7）细胞的剂量依赖性细胞毒性和细胞凋亡反应。我们进一步通过氧化应激探讨了 BiO NPs 细胞毒性的潜在机制。物理化学研究表明，BiO NPs 具有晶体结构和球形，平均粒径为 97nm。毒性研究表明，BiO NPs 在 50-300μg/ml 的浓度范围内，呈剂量依赖性降低细胞活力并诱导细胞膜损伤。BiO NPs 还干扰 MCF-7 细胞的细胞周期。BiO NPs 产生活性氧（ROS）、脂质过氧化增加、谷胱甘肽（GSH）减少和超氧化物歧化酶（SOD）酶活性降低，表明其发生了氧化应激反应。有趣的是，外源性抗氧化剂 N-乙酰半胱氨酸的补充几乎消除了 BiO NPs 诱导的氧化应激和细胞死亡的作用。我们还发现，BiO NPs 暴露诱导 MCF-7 细胞发生凋亡反应，这表明 Bax/Bcl-2 通路的调控受损。总之，我们发现 BiO NPs 通过调节 Bax/Bcl-2 通路来破坏氧化还原稳态，从而诱导 MCF-7 细胞的细胞毒性。本研究需要进一步研究来阐明 BiO NPs 在体内水平诱导毒性的潜在机制。
