Journal
TOXICOLOGY MECHANISMS AND METHODS
Volume 27, Issue 1, Pages 45-51Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/15376516.2016.1243183
Keywords
Phosgene; transepithelial electrical resistance; in vitro models; energy metabolism; pulmonary injury
Categories
Funding
- NIH/NIAID [Y1-A1-6179-02]
- USAMRICD [Y1-A1-6179-02]
Ask authors/readers for more resources
Therapeutic development against exposure to toxic gases is hindered by the lack of appropriate models to evaluate candidate compounds prior to animal efficacy studies. In this study, an in vitro, air-liquid interface exposure model has been tested to examine its potential application for screening treatments for phosgene (carbonyl chloride)-induced pulmonary injury. Epithelial cultures on Transwell (R) inserts, combined with a Vitrocell (R) exposure apparatus, provided a physiologically relevant exposure environment. Differentiated human bronchial epithelial (16HBE) cultures were exposed for 8min to phosgene ranging from 0 to 64ppm and assessed for changes in transepithelial electrical resistance (TEER, epithelial barrier integrity), cellular viability (XTT) and post-exposure (PE) cellular metabolic energy status. Exposure to phosgene concentrations >= 8ppm caused dose-dependent and significant decreases in TEER and XTT which did not recover within 24-h PE. In addition, at 64ppm the rate of oxidative glutamine metabolism was significantly inhibited at 6 and 24h after exposure. Glycolytic activities (glucose utilization and lactate production) were also inhibited, but to a lesser extent. Decreased glycolytic function can translate to insufficient energy sources to counteract barrier function failure. Consistent and sensitive markers of phosgene exposure were TEER, cell viability and decreased metabolism. As such, we have assessed an appropriate in vitro model of phosgene inhalation that produced quantifiable alterations in markers of lung cell metabolism and injury in human airway epithelial cells. Data indicate the suitability of this model for testing classes of anti-edemagenic compounds such as corticosteroids or phosphodiesterase inhibitors for evaluating phosgene therapeutics.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available