Kim Ji-Eun, Lee Somin, Lee Ah Young, Seo Hwi Won, Chae Chanhee, Cho Myung-Haing
Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University , Seoul , Korea .
Nanotoxicology. 2015;9(5):613-23. doi: 10.3109/17435390.2014.963186. Epub 2014 Sep 29.
The effects of multi-walled carbon nanotubes (MWCNTs) exposure have garnered great interest in the field of public health, due to the high aspect ratio of MWCNTs. Because of worldwide increases in obesity prevalence, nonalcoholic fatty liver disease (NAFLD) is now the most common prevalent liver disease and is considered to be a component of metabolic syndrome, which is a cluster of disorders that also includes dyslipidemia, diabetes mellitus, arteriosclerosis, and hypertension. Exposure to MWCNTs is known to be a risk factor for lung and cardiovascular diseases, but its effect on NAFLD is unknown. In this study, we investigated the effects of intratracheal exposure of two different types of MWCNTs, namely, pristine multi-walled carbon nanotubes (PMWCNTs) and acid-treated multi-walled carbon nanotubes (TMWCNTs), on liver pathogenesis. Direct instillation of a test material into the lungs has been employed as a quantitatively reliable alternative method of inhalation exposure. The 10% weight loss dose was assessed in three months of subchronic study and is defined here as the maximum tolerated dose (MTD) of PMWCNTs and TMWCNTs; by this metric, MTD for a 1-year exposure of MWCNTs was determined to be 0.1 mg/mouse. Mice exposed to PMWCNTs and TMWCNTs for one year developed a nonalcoholic steatohepatitis (NASH)-like phenotype, characterized by inflammation, hepatic steatosis, and fibrosis. Furthermore, PMWCNTs induced a more severe NASH-like phenotype than TMWCNTs, which was related to consistent up-regulation of interleukin (IL)-6 and plasminogen activator inhibitor (PAI)-1. Impaired cholesterol homeostasis, overexpression of NF-κBp65, and suppression of peroxisome proliferator-activated receptor gamma (PPARγ) in the liver were also observed.
由于多壁碳纳米管（MWCNTs）的高长径比，其暴露影响在公共卫生领域引起了极大关注。由于全球肥胖患病率上升，非酒精性脂肪性肝病（NAFLD）现已成为最常见的流行肝病，并被认为是代谢综合征的一个组成部分，代谢综合征是一组疾病，还包括血脂异常、糖尿病、动脉硬化和高血压。已知接触MWCNTs是肺部和心血管疾病的危险因素，但其对NAFLD的影响尚不清楚。在本研究中，我们研究了气管内暴露两种不同类型的MWCNTs，即原始多壁碳纳米管（PMWCNTs）和酸处理多壁碳纳米管（TMWCNTs）对肝脏发病机制的影响。将测试材料直接滴入肺部已被用作吸入暴露的一种定量可靠的替代方法。在为期三个月的亚慢性研究中评估了10%体重减轻剂量，在此将其定义为PMWCNTs和TMWCNTs的最大耐受剂量（MTD）；根据这一指标，MWCNTs一年暴露的MTD被确定为0.1mg/小鼠。暴露于PMWCNTs和TMWCNTs一年的小鼠出现了非酒精性脂肪性肝炎（NASH）样表型，其特征为炎症、肝脂肪变性和纤维化。此外，PMWCNTs诱导的NASH样表型比TMWCNTs更严重，这与白细胞介素（IL）-6和纤溶酶原激活物抑制剂（PAI）-1的持续上调有关。还观察到肝脏中胆固醇稳态受损、NF-κBp65过表达以及过氧化物酶体增殖物激活受体γ（PPARγ）受抑制。
