title: Mitigation of chlorine gas lung injury in rats by postexposure administration of sodium nitrite.
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 (Cl(2))-induced lung injury in rats. Rats were exposed to Cl(2) (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 F(2)-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 Cl(2) 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. F(2)-isoprostane levels increased at 6 and 24 h after Cl(2) exposure in NO(2)(-)- and saline-injected rats. This is the first demonstration that systemic NO(2)(-) administration mitigates airway and epithelial injury.
authors.affiliation: Departments of Environmental Health Sciences, Schools of Public Health and Medicine, University of Alabama at Birmingham, USA.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Yadav
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Doran
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Samal
authors.forename: Ruchita
authors.initials: R
authors.lastname: Sharma
authors.forename: Kokilavani
authors.initials: K
authors.lastname: Vedagiri
authors.forename: Edward M
authors.initials: EM
authors.lastname: Postlethwait
authors.forename: Giuseppe L
authors.initials: GL
authors.lastname: Squadrito
authors.forename: Michelle V
authors.initials: MV
authors.lastname: Fanucchi
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
authors.forename: Sadis
authors.initials: S
authors.lastname: Matalon
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002713:Chlorine; D028441:F2-Isoprostanes / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D055370:Lung Injury / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009585:Nitrogen Dioxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D012977:Sodium Nitrite / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D028441:F2-Isoprostanes; D002713:Chlorine; D012977:Sodium Nitrite; D009585:Nitrogen Dioxide; D010100:Oxygen