Assessment of inhaled acute ammonia-induced lung injury in rats
Assessment of inhaled acute ammonia-induced lung injury in rats
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DOI：
10.3109/08958378.2015.1136715
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发表时间：
2016-01-28
影响因子：
2.1
通讯作者：
Sciuto, Alfred M.
中科院分区：
文献类型：
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作者：
Perkins, Michael W.;Wong, Benjamin;Sciuto, Alfred M.
本研究检查了吸入氨后的急性毒性和肺损伤。雄性Sprague-Dawley大鼠（300-350 g）在定制头伸出暴露系统中暴露于9000、20 000、23 000、26 000、30 000或35 000 ppm氨20 min。使用傅里叶变换红外光谱（FTIR）气体分析仪监测并验证了所有氨浓度在3 min内达到稳态的暴露气氛。暴露于氨的动物导致观察到的中毒体征呈剂量依赖性增加，包括咀嚼和舔食增加、眼部刺激、流涎、流泪、口鼻分泌物和呼吸困难。通过概率单位分析确定，雄性大鼠在该头外吸入暴露模型中氨的LCt（50）为23 672 ppm（16 489 mg/m（3）），暴露时间为20分钟。暴露于20 000或23 000 ppm的氨导致显着的体重减轻24小时后曝光。所有接触氨的动物组的肺水肿均增加，并且在接触9000 ppm后尤为明显。支气管肺泡液（BALF）蛋白浓度显着增加后，暴露于20 000或23 000 ppm的氨相比，对照组。与对照组相比，暴露于20 000或23 000 ppm氨的动物的BAL细胞（BALC）死亡和总细胞计数增加。暴露于23 000 ppm氨后，血液和BALF中的白色血细胞、中性粒细胞和血小板的分类细胞计数显著增加。以下研究描述了用于测定急性氨诱导毒性的头外吸入暴露模型的验证;该模型将用于开发和评价提供呼吸和全身毒理学效应保护的潜在疗法。
This study examined acute toxicity and lung injury following inhalation exposure to ammonia. Male Sprague-Dawley rats (300-350 g) were exposed to 9000, 20 000, 23 000, 26 000, 30 000 or 35 000 ppm of ammonia for 20 min in a custom head-out exposure system. The exposure atmosphere, which attained steady state within 3 min for all ammonia concentrations, was monitored and verified using a Fourier transform infrared spectroscopy (FTIR) gas analyzer. Animals exposed to ammonia resulted in dose-dependent increases in observed signs of intoxication, including increased chewing and licking, ocular irritation, salivation, lacrimation, oronasal secretion and labored breathing. The LCt(50) of ammonia within this head-out inhalation exposure model was determined by probit analysis to be 23 672 ppm (16 489 mg/m(3)) for the 20 min exposure in male rats. Exposure to 20 000 or 23 000 ppm of ammonia resulted in significant body weight loss 24-h post-exposure. Lung edema increased in all ammonia-exposed animal groups and was significant following exposure to 9000 ppm. Bronchoalveolar fluid (BALF) protein concentrations significantly increased following exposure to 20 000 or 23 000 ppm of ammonia in comparison to controls. BAL cell (BALC) death and total cell counts increased in animals exposed to 20 000 or 23 000 ppm of ammonia in comparison to controls. Differential cell counts of white blood cells, neutrophils and platelets from blood and BALF were significantly increased following exposure to 23 000 ppm of ammonia. The following studies describe the validation of a head-out inhalation exposure model for the determination of acute ammonia-induced toxicity; this model will be used for the development and evaluation of potential therapies that provide protection against respiratory and systemic toxicological effects.