Kim Ji-Eun, Cho Myung-Haing
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Toxics. 2023 Apr 14;11(4):373. doi: 10.3390/toxics11040373.
Carbon nanotubes (CNTs) have gained much attention due to their superb properties, which make them promising options for the reinforcing composite materials with desirable mechanical properties. However, little is known about the linkage between lung exposure to nanomaterials and kidney disease. In this study, we compared the effects on the kidneys and aging for two different types of multiwall carbon nanotubes (MWCNTs): pristine MWCNTs (PMWCNTs) and acid-treated MWCNTs (TMWCNTs), with TMWCNTs being the preferred form for use as a composite material due to its superior dispersion properties. We used tracheal instillation and maximum tolerated dose (MTD) for both types of CNTs. MTD was determined as a 10% weight loss dose in a 3-month subchronic study, and the appropriate dosage for 1-year exposure was 0.1 mg/mouse. Serum and kidney samples were analyzed using ELISA, Western blot, and immunohistochemistry after 6 months and 1 year of treatment. PMWCNT-administered mice showed the activation of pathways for inflammation, apoptosis, and insufficient autophagy, as well as decreased serum Klotho levels and increased serum levels of DKK-1, FGF-23, and sclerostin, while TMWCNTs did not. Our study suggests that lung exposure to PMWCNTs can induce premature kidney aging and highlights a possible toxic effect of using MWCNTs on the kidneys in the industrial field, further highlighting that dispersibility can affect the toxicity of the nanotubes.
碳纳米管（CNTs）因其卓越的性能而备受关注，这使其成为具有理想机械性能的增强复合材料的有前景选择。然而，对于肺部暴露于纳米材料与肾脏疾病之间的联系却知之甚少。在本研究中，我们比较了两种不同类型的多壁碳纳米管（MWCNTs）对肾脏和衰老的影响：原始多壁碳纳米管（PMWCNTs）和酸处理多壁碳纳米管（TMWCNTs），由于其优异的分散性能，TMWCNTs是用作复合材料的首选形式。我们对两种类型的碳纳米管均采用气管滴注和最大耐受剂量（MTD）。在一项为期3个月的亚慢性研究中，MTD被确定为导致体重减轻10%的剂量，1年暴露的合适剂量为0.1mg/小鼠。在治疗6个月和1年后，使用酶联免疫吸附测定（ELISA）、蛋白质免疫印迹法（Western blot）和免疫组织化学对血清和肾脏样本进行分析。接受PMWCNT处理的小鼠表现出炎症、凋亡和自噬不足途径的激活，以及血清中klotho水平降低和DKK-1、FGF-23和硬化蛋白血清水平升高，而TMWCNTs则没有。我们的研究表明，肺部暴露于PMWCNTs可诱导肾脏早衰，并突出了在工业领域使用MWCNTs对肾脏可能产生的毒性作用，进一步强调分散性会影响纳米管的毒性。
