Mitigation of chlorine-induced lung injury by low-molecular-weight antioxidants.
Chlorine (Cl(2)) is a highly reactive oxidant gas used extensively in a number of industrial processes. Exposure to high concentrations of Cl(2) results in acute lung injury that may either resolve spontaneously or progress to acute respiratory failure. Presently, the pathophysiological sequelae associated with Cl(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(2) gas (184 or 400 ppm) for 30 min 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 Cl(2). Rats injected systemically with a mixture of AA, deferoxamine, and N-acetyl-L-cysteine before exposure to 184 ppm Cl(2) had normal levels of AA, lower levels of BALF albumin and normal arterial Po(2) and Pco(2) values. These findings suggest that Cl(2) inhalation damages both airway and alveolar epithelial tissues and that resulting effects were ameliorated by prophylactic administration of low-molecular-weight antioxidants.
Leustik
Martin
M
Department of Anesthesiology, University of Alabama at Birmingham, 901 19th Street South, Birmingham, AL 35205-3703, USA.
Doran
Stephen
S
Bracher
Andreas
A
Williams
Shawn
S
Squadrito
Giuseppe L
GL
Schoeb
Trenton R
TR
Postlethwait
Edward
E
Matalon
Sadis
S
D000142:Acidosis, Respiratory / Q000150:complications; D000388:Air; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid; D002713:Chlorine; D004801:Eosine Yellowish-(YS); D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006416:Hematoxylin; D000860:Hypoxia / Q000150:complications; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008970:Molecular Weight; D010313:Partial Pressure; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013500:Surface Tension / Q000187:drug effects
D000975:Antioxidants; D010743:Phospholipids; D011663:Pulmonary Surfactants; D002713:Chlorine; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin