Mechanisms and modification of chlorine-induced lung injury in animals

Academic Article

Abstract

  • Chlorine (Cl2) is a reactive oxidant gas used extensively in industrial processes. Exposure of both humans and animals to high concentrations of Cl2 results in acute lung injury, which may resolve spontaneously or progress to acute respiratory failure. Injury to airway andalveolar epitheliummayresult from chemical reactions of Cl2, from HOCl (the hydrolysis product of Cl2), and/or from the various reaction products, such as chloramines, that are formed from the reactions of these chlorinating species with biological molecules. Subsequent reactions may initiate self-propagating reactions and induce the production of inflammatory mediators compounding injury to pulmonary surfactant, ion channels, and components of lung epithelial and airway cells. Low-molecular-weight antioxidants, such as ascorbate, glutathione, and urate, present in the lung epithelial lining fluid and tissue, remove Cl2 and HOCl and thus decrease injury to critical target biological targets. However, levels of lung antioxidants of animals exposed to Cl2 in concentrations likely to be encountered in the vicinity of industrial accidents decrease rapidly and irreversibly. Our measurements show that prophylactic administration of a mixture containing ascorbate and desferal Nacetyl-cysteine, a precursor of reduced glutathione, prevents Cl2-induced injury to the alveolar epitheliumof rats exposed to Cl2. The clinical challenge is to deliver sufficient quantities of antioxidants noninvasively, after Cl 2 exposure, to decrease morbidity and mortality.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Yadav AK; Bracher A; Doran SF; Leustik M; Squadrito GL; Postlethwait EM; Matalon S
  • Start Page

  • 278
  • End Page

  • 283
  • Volume

  • 7
  • Issue

  • 4