Department of Pharmaceutical Toxicology, Hacettepe University Faculty of Pharmacy, Ankara, Turkey.
Department of Pharmaceutical Toxicology, Bahçeşehir University School of Pharmacy, İstanbul, Turkey.
Toxicol Mech Methods. 2024 Feb;34(2):109-121. doi: 10.1080/15376516.2023.2259980. Epub 2024 Jan 29.
Nanoparticles (NPs) are particles of matter that are between 1 to 100 nm in diameter. They are suggested to cause toxic effects in both humans and environment thorough different mechanisms. However, their toxicity profile may be different from the parent material. Titanium dioxide (TiO) NPs are widely used in cosmetic, pharmaceutical and food industries. As a white pigment, the use of TiO is used in food coloring, industrial paints, clothing and UV filters has increased tremendously in recent years. Melatonin, on the other hand, is a well-known antioxidant and may prevent oxidative stress caused by a variety of different substances, including NPs. In the current study, we aimed to comparatively investigate the effects of normal-sized TiO (220 nm) and nano-sized TiO (21 nm) on cytopathology, cytotoxicity, oxidative damage (lipid peroxidation, protein oxidation and glutathione), genotoxicity (8-hydroxydeoxyguanosine), apoptosis (caspase 3, 8 and 9) and epigenetic alterations (global DNA methylation, H3 acetylation) on 3T3 fibroblast cells. In addition, the possible protective effects of melatonin, which is known to have strong antioxidant effects, against the toxicity of TiO were also evaluated. Study groups were: a. the control group; b. melatonin group; c. TiO group; d. nano-sized TiO group; e. TiO + melatonin group and f. nano-sized TiO + melatonin group. We observed that both normal-sized and nano-sized TiO NPs showed significant toxic effects. However, TiO NPs caused higher DNA damage and global DNA methylation compared to normal-sized TiO whereas normal-sized TiO led to lower H3 acetylation vs. TiO NPs. Melatonin showed partial protective effect against the toxicity caused by TiO NPs.
纳米粒子（NPs）是指直径在 1 至 100nm 之间的物质颗粒。它们被认为通过不同的机制在人类和环境中引起毒性作用。然而，它们的毒性特征可能与母体材料不同。二氧化钛（TiO）NPs 广泛应用于化妆品、制药和食品工业。作为一种白色颜料，TiO 被用于食品着色、工业涂料、服装和紫外线过滤器，近年来使用量大大增加。褪黑素是一种众所周知的抗氧化剂，可预防包括 NPs 在内的多种不同物质引起的氧化应激。在目前的研究中，我们旨在比较研究正常大小的 TiO（220nm）和纳米大小的 TiO（21nm）对细胞病理学、细胞毒性、氧化损伤（脂质过氧化、蛋白质氧化和谷胱甘肽）、遗传毒性（8-羟基脱氧鸟苷）、细胞凋亡（caspase 3、8 和 9）和表观遗传改变（全基因组 DNA 甲基化、H3 乙酰化）对 3T3 成纤维细胞的影响。此外，还评估了褪黑素（已知具有很强的抗氧化作用）对 TiO 毒性的可能保护作用。研究组包括：a. 对照组；b. 褪黑素组；c. TiO 组；d. 纳米 TiO 组；e. TiO+褪黑素组和 f. 纳米 TiO+褪黑素组。我们观察到，正常大小和纳米大小的 TiO NPs 都表现出显著的毒性作用。然而，与正常大小的 TiO 相比，纳米大小的 TiO 导致更高的 DNA 损伤和全基因组 DNA 甲基化，而正常大小的 TiO 导致的 H3 乙酰化水平低于 TiO NPs。褪黑素对 TiO NPs 引起的毒性表现出部分保护作用。
