Division of Pharmacology and Toxicology, Defence Research & Development Establishment, Gwalior, India.
Environ Toxicol Pharmacol. 2012 Nov;34(3):977-84. doi: 10.1016/j.etap.2012.07.009. Epub 2012 Jul 31.
Inhalation toxicity of silicon dioxide aerosol (150, 300 mg/m(3)) daily over a period of 28 days was carried out in rats. The changes in respiratory variables during the period of exposure were monitored using a computer programme that recognizes the modifications of the breathing pattern. Exposure to the aerosol caused a time dependent decrease in tidal volume, with an increase in respiratory frequency compared to the control. Biochemical variables and histopathological observation were noted at 28th day following the start of exposure. Biochemical markers of silica induced lung injury like plasma alkaline phosphatase, lactate dehydrogenase and angiotensine converting enzyme activities increased in a concentration dependent manner compared to control. Increase in the plasma enzymatic activities indicates endothelial lung damage, increased lung membrane permeability. Histopathological observation of the lungs confirmed concentration dependent granulomatous inflammation, fibrosis and proteinacious degeneration. Aggregates of mononuclear cells with entrapped silica particles circumscribed by fibroblast were observed in 300 mg/m(3) silica aerosol exposed group at higher magnification. Decrease in tidal volume and increase in respiratory frequency might be due to the thickening of the alveolar wall leading to a decreased alveolar volume and lowered elasticity of the lung tissue. The trends in histological and biochemical data are in conformity with the respiratory data in the present study. This study reports for the first time, the changes in respiratory variables during silica aerosol exposure over a period of 28 days.
在大鼠身上进行了为期 28 天、每天吸入二氧化硅气溶胶(150、300mg/m(3))的吸入毒性研究。使用一种能够识别呼吸模式变化的计算机程序来监测暴露期间呼吸变量的变化。与对照组相比,暴露于气溶胶会导致潮气量随时间的推移而减少,呼吸频率增加。在暴露开始后的第 28 天,观察了生化变量和组织病理学观察。与对照组相比,二氧化硅诱导的肺损伤的生化标志物,如血浆碱性磷酸酶、乳酸脱氢酶和血管紧张素转换酶活性呈浓度依赖性增加。血浆酶活性的增加表明内皮肺损伤、肺膜通透性增加。肺组织病理学观察证实了浓度依赖性的肉芽肿性炎症、纤维化和蛋白变性。在 300mg/m(3)二氧化硅气溶胶暴露组中,以更高的放大倍数观察到被成纤维细胞包围的单核细胞聚集物中含有二氧化硅颗粒。潮气量的减少和呼吸频率的增加可能是由于肺泡壁变厚导致肺泡体积减少和肺组织弹性降低所致。组织学和生化数据的趋势与本研究中的呼吸数据一致。本研究首次报道了在 28 天的二氧化硅气溶胶暴露期间呼吸变量的变化。