Hong Fashui, Zhou Yaoming, Zhou Yingjun, Wang Ling
Department of Food, Jiangsu Collaborative Innovation Center of Regional Modern Agriculture and Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.
Department of Food, Laboratory for Food Safety and Nutritional Function, Huaiyin Normal University, Huaian, 223300, China.
Environ Toxicol. 2017 Oct;32(10):2234-2243. doi: 10.1002/tox.22439. Epub 2017 Jun 24.
Titanium dioxide nanoparticles (TiO NPs) have been extensively used in industry, medicine, and daily life, and have shown potential toxic effects for animals or humans. We noted that the effects of TiO NPs on the immune system and its mechanism of action in animals or humans have not been elucidated. Thus, mice were exposed to the TiO NPs (0, 1.25, 2.5, or 5 mg kg body weight) for 9 consecutive months. Exposure to TiO NPs was accumulated in the thymus, leading to a decrease in body weight and increases in the weight of the thymus or thymus indices. In the blood, exposure to TiO NPs significantly decreased white blood cell, red blood cell, reticulocyte, haemoglobin, and mean corpuscular haemoglobin concentration; and increased mean corpuscular volume, mean corpuscular haemoglobin, platelets, and mean platelet volume. The reductions of lymphocyte subsets, including CD3+, CD4+, CD8+, B cell, and natural killer cell, were observed in the TiO NP-treated mouse thymus. Appearance of starry-sky aspect of the cortex that is given by the body of macrophages, bleeding, severe hemolysis or congestion, fatty degeneration, and cell apoptosis or necrosis were observed in the thymus following TiO NPs exposure. Importantly, TiO NPs increased expression of nucleic factor-κB(NF-κB), IκB kinase1/2, interleukin-1β, interleukin -4, regulated upon activation normal T-cell expressed and secreted, cyclooxygenase 2, neutrophil gelatinase-associated lipocalin, purinergic receptors-7, interferon-inducible protein 10, hypoxia inducible factor 1-α, p-c-Jun N-terminal kinase, p-p38, and p-extracellular signal-regulated kinase 1/2 protein, respectively; whereas suppressed expression of IκB, peroxisome proliferater-activated receptor-γ, trefoil factor 1, peroxisome proliferator activated receptor gamma coactivator-1α, and prostaglandin E2 proteins in the thymus, respectively. Taken together, these results suggest that TiO NPs exerts toxic effects on lymphoid organs and T cell and innate immune cell homeostasis in mice and that these immunotoxic potential effects may result from the activation of NF-κB-mediated mitogen-activated protein kinases (MAPKs) pathway.
二氧化钛纳米颗粒（TiO NPs）已在工业、医学和日常生活中广泛使用，并已显示出对动物或人类的潜在毒性作用。我们注意到，TiO NPs对动物或人类免疫系统的影响及其作用机制尚未阐明。因此，将小鼠连续9个月暴露于TiO NPs（0、1.25、2.5或5 mg/kg体重）。暴露于TiO NPs会在胸腺中蓄积，导致体重下降以及胸腺重量或胸腺指数增加。在血液中，暴露于TiO NPs会显著降低白细胞、红细胞、网织红细胞、血红蛋白和平均红细胞血红蛋白浓度；并增加平均红细胞体积、平均红细胞血红蛋白、血小板和平均血小板体积。在经TiO NP处理的小鼠胸腺中观察到淋巴细胞亚群减少，包括CD3 +、CD4 +、CD8 +、B细胞和自然杀伤细胞。在TiO NPs暴露后的胸腺中观察到由巨噬细胞体呈现的皮质星空样外观、出血、严重溶血或充血、脂肪变性以及细胞凋亡或坏死。重要的是，TiO NPs分别增加了核因子-κB（NF-κB）、IκB激酶1/2、白细胞介素-1β、白细胞介素-4、活化正常T细胞表达和分泌的调节因子、环氧化酶2、中性粒细胞明胶酶相关脂质运载蛋白、嘌呤能受体-7、干扰素诱导蛋白10、缺氧诱导因子1-α、磷酸化c-Jun氨基末端激酶、磷酸化p38和磷酸化细胞外信号调节激酶1/2蛋白的表达；而分别抑制了胸腺中IκB、过氧化物酶体增殖物激活受体-γ、三叶因子1、过氧化物酶体增殖物激活受体γ共激活因子-1α和前列腺素E2蛋白的表达。综上所述，这些结果表明TiO NPs对小鼠的淋巴器官以及T细胞和先天免疫细胞稳态产生毒性作用，并且这些免疫毒性潜在作用可能是由NF-κB介导的丝裂原活化蛋白激酶（MAPKs）途径的激活所致。
