在吸入和气管内滴注研究中,经过充分表征的富勒烯的致炎作用。
Inflammogenic effect of well-characterized fullerenes in inhalation and intratracheal instillation studies.
机构信息
Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
出版信息
Part Fibre Toxicol. 2010 Mar 14;7:4. doi: 10.1186/1743-8977-7-4.
BACKGROUND
We used fullerenes, whose dispersion at the nano-level was stabilized by grinding in nitrogen gas in an agitation mill, to conduct an intratracheal instillation study and an inhalation exposure study. Fullerenes were individually dispersed in distilled water including 0.1% Tween 80, and the diameter of the fullerenes was 33 nm. These suspensions were directly injected as a solution in the intratracheal instillation study. The reference material was nickel oxide in distilled water. Wistar male rats intratracheally received a dose of 0.1 mg, 0.2 mg, or 1 mg of fullerenes and were sacrificed after 3 days, 1 week, 1 month, 3 months, and 6 months. In the inhalation study, Wistar rats were exposed to fullerene agglomerates (diameter: 96 +/- 5 nm; 0.12 +/- 0.03 mg/m3; 6 hours/days for 5 days/week) for 4 weeks and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inflammatory responses and gene expression of cytokine-induced neutrophil chemoattractants (CINCs) were examined in rat lungs in both studies.
RESULTS
In the intratracheal instillation study, both the 0.1 mg and 0.2 mg fullerene groups did not show a significant increase of the total cell and neutrophil count in BALF or in the expression of CINC-1,-2alphabeta and-3 in the lung, while the high-dose, 1 mg group only showed a transient significant increase of neutrophils and expression of CINC-1,-2alphabeta and -3. In the inhalation study, there were no increases of total cell and neutrophil count in BALF, CINC-1,-2alphabeta and-3 in the fullerene group.
CONCLUSION
These data in intratracheal instillation and inhalation studies suggested that well-dispersed fullerenes do not have strong potential of neutrophil inflammation.
背景
我们使用富勒烯,通过在搅拌磨机中在氮气中研磨使其在纳米级分散,进行了气管内滴注研究和吸入暴露研究。富勒烯单独分散在包含 0.1%吐温 80 的蒸馏水中,富勒烯的直径为 33nm。这些悬浮液直接作为溶液在气管内滴注研究中注射。参比材料为蒸馏水中的氧化镍。Wistar 雄性大鼠气管内接受 0.1mg、0.2mg 或 1mg 富勒烯的剂量,并在 3 天、1 周、1 个月、3 个月和 6 个月后处死。在吸入研究中,Wistar 大鼠暴露于富勒烯团聚体(直径:96 +/- 5nm;0.12 +/- 0.03mg/m3;6 小时/天,每周 5 天)4 周,在暴露结束后 3 天、1 个月和 3 个月处死。在两项研究中,均检查了大鼠肺部的炎症反应和细胞因子诱导的中性粒细胞趋化因子(CINCs)的基因表达。
结果
在气管内滴注研究中,0.1mg 和 0.2mg 富勒烯组 BALF 中的总细胞和中性粒细胞计数或肺中的 CINC-1、-2alphabeta 和-3 的表达均无显著增加,而高剂量 1mg 组仅表现出短暂的显著增加中性粒细胞和 CINC-1、-2alphabeta 和-3 的表达。在吸入研究中,富勒烯组 BALF 中的总细胞和中性粒细胞计数、CINC-1、-2alphabeta 和-3 均无增加。
结论
气管内滴注和吸入研究中的这些数据表明,分散良好的富勒烯没有强烈的中性粒细胞炎症潜力。