Mitigation of chlorine-induced lung injury by low-molecular-weight antioxidants

Chlorine ([Cl.sub.2]) is a highly reactive oxidant gas used extensively in a number of industrial processes. Exposure to high concentrations of C12 results in acute lung injury that may either resolve spontaneously or progress to acute respiratory failure. Presently, the pathophysiological sequelae associated with [Cl.sub.2]-induced acute lung injury in conscious animals, as well as the cellular and biochemical mechanisms involved, have not been elucidated. We exposed conscious Sprague-Dawley rats to [Cl.sub.2] gas (184 or 400 ppm) for 30 rain in environmental chambers and then returned them to room air. At 1 h after exposure, rats showed evidence of arterial hypoxemia, respiratory acidosis, increased levels of albumin, IgG, and IgM in bronchoalveolar lavage fluid (BALF), increased BALF surfactant surface tension, and significant histological injury to airway and alveolar epithelia. These changes were more pronounced in the 400-ppm-exposed rats. Concomitant decreases of ascorbate (AA) and reduced glutathione (GSH) were also detected in both BALF and lung tissues. In contrast, heart tissue AA and GSH content remained unchanged. These abnormalities persisted 24 h after exposure in rats exposed to 400 ppm C12. Rats injected systemically with a mixture of AA, deferoxamine, and N-acetyl-L-cysteine before exposure to 184 ppm [Cl.sub.2] had normal levels of AA, lower levels of BALF albumin and normal arterial P[o.sub.2] and Pc[o.sub.2] values. These findings suggest that [Cl.sub.2] inhalation damages both airway and alveolar epithelial tissues and that resulting effects were ameliorated by prophylactic administration of low-molecular-weight antioxidants. ascorbate; N-acetyl-L-cysteine; deferoxamine; arterial blood gases; alveolar permeability; minimum surface tension; airway epithelium; histology