Mitigation of chlorine gas lung injury in rats by postexposure administration of sodium nitrite

Academic Article

Abstract

  • Nitrite (NO-2) has been shown to limit injury to the heart, liver, and kidneys in various models of ischemia-reperfusion injury. Potential protective effects of systemic NO-2 in limiting lung injury or enhancing repair have not been documented. We assessed the efficacy and mechanisms by which postexposure intraperitoneal injections of NO-2 mitigate chlorine (Cl2)-induced lung injury in rats. Rats were exposed to Cl2 (400 ppm) for 30 min and returned to room air. NO-2 (1 mg/kg) or saline was administered intraperitoneally at 10 min and 2, 4, and 6 h after exposure. Rats were killed at 6 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-to-dry lung weight ratio. Lipid peroxidation was assessed by measurement of lung F2-isoprostanes. Rats developed severe, but transient, hypoxemia. A significant increase of protein concentration, neutrophil numbers, airway epithelia in the BAL, and lung wet-to-dry weight ratio was evident at 6 h after Cl2 exposure. Quantitative morphology revealed extensive lung injury in the upper airways. Airway epithelial cells stained positive for terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL), but not caspase-3. Administration of NO-2 resulted in lower BAL protein levels, significant reduction in the intensity of the TUNEL-positive cells, and normal lung wet-to-dry weight ratios. F2-isoprostane levels increased at 6 and 24 h after Cl2 exposure in NO-2 and saline-injected rats. This is the first demonstration that systemic NO-2 administration mitigates airway and epithelial injury. © 2011 the American Physiological Society.
  • Digital Object Identifier (doi)

    Author List

  • Yadav AK; Doran SF; Samal AA; Sharma R; Vedagiri K; Postlethwait EM; Squadrito GL; Fanucchi MV; Jackson Roberts L; Patel RP
  • Volume

  • 300
  • Issue

  • 3