Assessment of inhaled acute ammonia-induced lung injury in rats

Abstract

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 LCt50 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.

Ammonia promotes endothelial cell survival via the heme oxygenase-1-mediated release of carbon monoxide

“…This observation is consistent with other studies performed in mouse and rat brain endothelial cell lines [63,64], suggesting that the toxic effects of ammonia may be cell-specific. Surprisingly, we show that ammonia pretreatment markedly reduces endothelial cell death in response to TNFα and cycloheximide.…”

Chronic exposure to ammonia induces oxidative stress and enhanced glycolysis in lung of piglets

“…High‐concentration ammonia exposure can induce the tracheal tissue injury and noncoding RNAs play a crucial role in this process 13 . Study on acute ammonia toxicity in rats found the lung injuries and the significantly increased protein concentration and total cell counts from bronchoalveolar fluid, as well as the increased white blood cells, neutrophils, and platelets from blood following inhalation exposure to ammonia 14 . Many researches have also found that ammonia can induce oxidative stress and cell apoptosis.…”

Sampling and analysis of airborne ammonia in workplaces of China

“…Personal exposure to ammonia at a certain concentration could cause a strong stimulating and corrosive effect on human eyes, nose, throat, and skin. 3,4 Exposure to ammonia at the concentration of about 20-95 mg/m 3 in the urea fertilizer factory could induce acute respiratory symptoms and acute decline in lung function. 2 Chronic ammonia inhalation could also cause pulmonary fibrosis and interstitial lung disease.…”

“…Its widespread usage makes it a common occupational hazard factor in the air of workplace and creates a large potential for worker occupational exposure. Personal exposure to ammonia at a certain concentration could cause a strong stimulating and corrosive effect on human eyes, nose, throat, and skin . Exposure to ammonia at the concentration of about 20‐95 mg/m 3 in the urea fertilizer factory could induce acute respiratory symptoms and acute decline in lung function .…”