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经定向气流鼻腔暴露室吸入 ZnO 纳米颗粒和甲苯混合物后引发的肺部纤维化反应

Pulmonary fibrotic response to inhalation of ZnO nanoparticles and toluene co-exposure through directed flow nose only exposure chamber.

机构信息

Laboratory of Chromatin Biology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) , Mohali, Punjab , India.

出版信息

Inhal Toxicol. 2013 Nov;25(13):703-13. doi: 10.3109/08958378.2013.839765.

DOI:10.3109/08958378.2013.839765
PMID:24255948
Abstract

The increasing use of Zinc Oxide nanoparticles (ZnONPs) in paint industry is not supplemented with adequate toxicology data. This report focuses on the fibrogenic toxicity caused due to co-exposure of ZnONPs and toluene in male Wistar rats, exposed for 28 days, through directed flow nose only exposure chamber. The rats were grouped as air control, toluene control (200 ppm), zinc oxide control (10 mg/m(3)), low dose co-exposed (5 mg/m(3) ZnO and 200 ppm of toluene) and high dose co-exposed (10 mg/m(3) of ZnO and 200 ppm of toluene). Our study demonstrates that co-exposure of ZnONPs and toluene (as in paint industry), even at their respective permissible exposure level (5 mg/m(3) for ZnO and 200 ppm for toluene) have the potential to produce a progressive inflammatory and fibrotic response in the alveolar tissues of the lungs. We observed a significant increase in inflammatory markers in BAL fluid and elevated malondialdehyde (MDA) levels with lower levels of intracellular reduced glutathione (GSH) in lungs of rats of co-exposed group. Significant increase in the levels of pro-inflammatory mediators (IL-6, Ikβα, Cox-II, p-NF-κB) in lung tissues also indicated pulmonary damage. To best of our knowledge this is the first study which highlights the toxicity of co-exposed ZnO NPs and toluene.

摘要

氧化锌纳米粒子(ZnONPs)在涂料行业中的应用日益增加,但与之配套的毒理学数据却严重不足。本报告重点关注了在雄性 Wistar 大鼠中,通过定向流动鼻暴露室,同时暴露于 ZnONPs 和甲苯所引起的纤维生成毒性。将大鼠分为空气对照组、甲苯对照组(200ppm)、氧化锌对照组(10mg/m³)、低剂量共同暴露组(5mg/m³ ZnO 和 200ppm 甲苯)和高剂量共同暴露组(10mg/m³ ZnO 和 200ppm 甲苯)。我们的研究表明,即使在各自允许的暴露水平(5mg/m³ ZnO 和 200ppm 甲苯)下,ZnONPs 和甲苯(如在涂料行业中)的共同暴露也有可能在肺部肺泡组织中产生进行性炎症和纤维化反应。我们观察到,共同暴露组大鼠的 BAL 液中炎症标志物显著增加,肺组织中丙二醛(MDA)水平升高,细胞内还原型谷胱甘肽(GSH)水平降低。肺组织中促炎介质(IL-6、Ikβα、Cox-II、p-NF-κB)水平的显著增加也表明存在肺损伤。据我们所知,这是第一项强调共同暴露的 ZnO NPs 和甲苯毒性的研究。

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