Morphology and Pathology Department, Federal University of São Carlos, São Carlos, Brazil.
Center of Development of Functional Materials (CDMF), Federal University of São Carlos, São Carlos, Brazil.
Toxicol Mech Methods. 2022 Mar;32(3):213-223. doi: 10.1080/15376516.2021.1994075. Epub 2021 Nov 9.
The extensive use of titanium dioxide nanoparticles (TiO NPs) in cosmetics, food, personal care products, and industries brought concerns about their possible harmful effects. Nowadays it has become important to assess TiO NPs toxic effects as a way to understand their primary risks. In the cellular environment, after cell uptake, TiO NPs were described to induce reactive oxygen species (ROS) production, unbalance oxidative state, and activate apoptosis in several cell lines. Therefore, we aimed to evaluate the cytotoxicity and genotoxicity of a new TiO NP surface-functionalized with sodium carboxylic ligands in a murine fibroblast cell line (LA-9). TEM and DLS analyses were performed to define nanoparticle physicochemical characteristics. We evaluated the metabolic activity and LDH released after 24 h exposition to determine cytotoxic effects. Also, we evaluated DNA damage, intracellular reactive oxygen species (ROS) production, and apoptosis induction after 24 h exposure. The TiO NP impaired the cell membrane integrity at 1000 μg/mL, induced intracellular ROS production and late apoptosis at 24 h. The genotoxic effects were observed at all conditions tested at 24 h. Indeed, in fibroblasts exposed at 100 μg/mL was observed early apoptosis cells. The intracellular ROS content was increased in a dose-dependent manner. Thus, short-term exposure to TiO NP promoted cytotoxicity, genotoxicity and activated apoptosis pathways based on the potential role of oxygen species in the fibroblasts cell line.
二氧化钛纳米粒子(TiO NPs)在化妆品、食品、个人护理产品和工业中的广泛应用引起了人们对其可能产生的有害影响的关注。如今,评估 TiO NPs 的毒性作用以了解其主要风险变得尤为重要。在细胞环境中,细胞摄取后,TiO NPs 被描述为在几种细胞系中诱导活性氧(ROS)的产生、氧化状态失衡和激活细胞凋亡。因此,我们旨在评估一种新的 TiO NP 的细胞毒性和遗传毒性,该纳米粒子表面功能化有羧酸钠配体,在小鼠成纤维细胞系(LA-9)中。进行 TEM 和 DLS 分析以确定纳米颗粒的物理化学特性。我们评估了 24 小时暴露后细胞代谢活性和 LDH 的释放,以确定细胞毒性作用。还评估了 24 小时暴露后 DNA 损伤、细胞内活性氧(ROS)的产生和细胞凋亡的诱导。1000μg/mL 时 TiO NP 破坏细胞膜完整性,24 小时时诱导细胞内 ROS 产生和晚期细胞凋亡。在 24 小时时,在所有测试条件下均观察到遗传毒性作用。事实上,在暴露于 100μg/mL 的成纤维细胞中观察到早期凋亡细胞。细胞内 ROS 含量呈剂量依赖性增加。因此,TiO NP 的短期暴露会促进细胞毒性、遗传毒性,并激活基于氧物种在成纤维细胞系中作用的细胞凋亡途径。