Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon nanotubes
Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon nanotubes
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DOI：
10.1016/j.tox.2008.12.023
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发表时间：
2009-03-29
期刊：
影响因子：
4.5
通讯作者：
Shvedova, A. A.
中科院分区：
文献类型：
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作者：
Murray, A. R.;Kisin, E.;Shvedova, A. A.
单壁碳纳米管（SWCNT）是一种具有独特电子力学性能的新型材料。极小的尺寸（直径约为1纳米）使它们的化学和物理性质独一无二。各种不同的技术可用于生产swcnts；然而，最常见的是通过催化铁颗粒支撑的气态碳分子的歧化（高压CO转化，HiPCO）。swcnts的物理性质可能导致在暴露的皮肤上沉积后渗透皮肤。这种皮肤沉积提供了一种暴露途径，这在评估swcnts毒性时是重要的考虑因素。swcnts对皮肤的影响在很大程度上是未知的。我们假设swcnts可能对皮肤有毒。我们进一步假设，swcnts的毒性可能取决于swcnts的金属（特别是铁）含量，通过金属与皮肤相互作用、启动氧化应激和诱导氧化还原敏感转录因子的能力，从而影响/导致炎症。为了验证这一假设，我们在体外和体内使用表皮细胞FT工程皮肤、小鼠表皮细胞（JB6 P+）和免疫能力无毛SKH-1小鼠评估了swcnts的作用。暴露于swcnts的工程皮肤显示表皮厚度增加，真皮成纤维细胞的积累和激活导致胶原蛋白增加以及促炎细胞因子的释放。JB6 P+细胞暴露于未纯化的swcnts（30%铁）导致产生ESR可检测的羟基自由基，并引起AP-1的显著剂量依赖性激活。当将部分纯化的swcnts（0.23%铁）引入细胞时，未检测到AP-1激活的显著变化。然而，暴露于未纯化和部分纯化的swcnts时，NF κ B以剂量依赖性的方式被激活。SKH-1小鼠局部暴露于未纯化swcnts（5天，每日剂量分别为40 μ g/只、80 μ g/只或160 μ g/只）可引起氧化应激、谷胱甘肽消耗、蛋白硫醇和羰基氧化、髓过氧化物酶活性升高、真皮细胞数量增加以及因多形核白细胞（pmn）和肥大细胞积累而导致的皮肤增厚。总之，这些数据表明，局部暴露于未纯化的swcnts，诱导自由基生成，氧化应激和炎症，从而导致皮肤毒性。爱思唯尔爱尔兰有限公司出版。
Single-walled carbon nanotubes (SWCNT) representa novel material with unique electronic and mechanical properties. The extremely small size (similar to 1 nm diameter) renders their chemical and physical properties unique. A variety of different techniques are available for the production of SWCNT; however, the most common is via the disproportionation of gaseous carbon molecules supported on catalytic iron particles (high-pressure CO conversion, HiPCO). The physical nature of SWCNT may lead to dermal penetration following deposition on exposed skin. This dermal deposition provides a route of exposure which is important to consider when evaluating SWCNT toxicity. The dermal effects of SWCNT are largely unknown. We hypothesize that SWCNT may be toxic to the skin. We further hypothesize that SWCNT toxicity may be dependent upon the metal (particularly iron) content of SWCNT via the metal's ability to interact with the skin, initiate oxidative stress, and induce redox-sensitive transcription factors thereby affecting/leading to inflammation. To test this hypothesis, the effects of SWCNT were assessed both in vitro and in vivo using EpiDerm FT engineered skin, murine epidermal cells (JB6 P+), and immune-competent hairless SKH-1 mice. Engineered skin exposed to SWCNT showed increased epidermal thickness and accumulation and activation of dermal fibroblasts which resulted in increased collagen as well as release of pro-inflammatory cytokines. Exposure of JB6 P+ cells to unpurified SWCNT (30% iron) resulted in the production of ESR detectable hydroxyl radicals and caused a significant dose-dependent activation of AP-1. No significant changes in AP-1 activation were detected when partially purified SWCNT (0.23% iron) were introduced to the cells. However, NF kappa B was activated in a dose-dependent fashion by exposure to both unpurified and partially purified SWCNT. Topical exposure of SKH-1 mice (5 days, with daily doses of 40 mu g/mouse, 80 mu g/mouse, or 160 mu g/mouse) to unpurified SWCNT caused oxidative stress, depletion of glutathione, oxidation of protein thiols and carbonyls, elevated myeloperoxidase activity, an increase of dermal cell numbers, and skin thickening resulting from the accumulation of polymorphonuclear leukocytes (PMNs) and mast cells. Altogether, these data indicated that topical exposure to unpurified SWCNT, induced free radical generation, oxidative stress, and inflammation, thus causing dermal toxicity. Published by Elsevier Ireland Ltd.