MITIGATION OF CHLORINE GAS LUNG INJURY IN RATS BY POST EXPOSURE ADMINISTRATION OF SODIUM NITRITE

Nitrite (NO2-) has been shown to limit injury to the heart, liver and kidneys in various models of ischemia-reperfusion injury. Currently, potential protective effects of systemic NO2- in limiting lung injury or enhancing repair have not been documented. We assessed the efficacy and mechanisms by which post-exposure intra-peritoneal injections of NO2- mitigate chlorine (Cl2) induced lung injury in rats. Rats were exposed to Cl2 (400 ppm) for 30 minutes and returned to room air. Nitrite (1mg/Kg) or saline were administered intraperitoneally at 10 min, 2, 4 and 6 hrs post exposure. Rats were sacrificed at 6 hrs or 24 h. Injury to airway and alveolar epithelia was assessed by quantitative morphology, protein concentrations, number of cells in bronchoalveolar lavage (BAL) and wet/dry lung weights. Lipid peroxidation was assessed by measuring lung F2-isoprostanes. Rats developed severe but transient hypoxemia. A significant increase of protein concentration, neutrophils numbers, airway epithelia in the BAL, and lung wet/dry weights was evident at 6 hrs post-Cl2 exposure. Quantitative morphology revealed extensive lung injury in the upper airways. Airway epithelial cells stained positive for TUNEL, but not caspase-3. Administration of NO2- resulted in lower BAL protein levels, significant reduction in the intensity of the TUNEL positive cells and normal values of lung wet/dry weights. F2-isoprostane levels increased at six and 24 h post Cl2 exposure in both NO2- and saline injected rats. This is the first demonstration that systemic NO2- administration mitigates airway and epithelial injury.

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