Hypoxanthine and oxygen induced lung injury: a possible basic mechanism of tissue damage?
Lung injury was induced in young rats by a continuous infusion of hypoxanthine intravenously and breathing 100% oxygen for 48 h (group 1). Control animals were rats infused glucose and breathing 100% oxygen (group 2), rats infused hypoxanthine in room air (group 3), and untreated rats (group 4). In group 1 rats interstitial and alveolar edema was found with a tendency toward marked margination of polymorphonuclear neutrophils in small vessels (P less than 0.025 compared with group 2). The main elastase inhibitor alpha 1-antitrypsin (alpha-1-PI) was significantly elevated in group 1; 2-, 3- and 5-fold, respectively, when compared with groups 2, 3, and 4. The surfactant phospholipids from alveolar lavage were normal in all groups. The protein-rich fraction of the lavage fluid from group 1 rats inactivated, however, the surface properties of lung surfactant. Minimum surface tension in group 1 rats was 14.5 dyn/cm compared with 7.0 dyn/cm in group 2, 2.9 dyn/cm in group 3 and 3.5 dyn/cm in group 4 (P less than 0.05, group 1 and 2 versus 4). We conclude that the combination of hypoxanthine and high levels of oxygen causes lung injury, possibly via free oxygen radicals. We discuss the possibility that these findings demonstrate a basic pathogenetic mechanism for the hypoxic-hyperoxic insult and can contribute to the understanding of pathogenesis of a variety of diseases both in pediatrics and adult medicine.
D000818:Animals; D005260:Female; D005609:Free Radicals; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000633:toxicity*; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D010100:Oxygen / Q000633:toxicity*; D010196:Pancreatic Elastase / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D005609:Free Radicals; D007042:Hypoxanthines; D010743:Phospholipids; D011663:Pulmonary Surfactants; D000515:alpha 1-Antitrypsin; D019271:Hypoxanthine; D010196:Pancreatic Elastase; D010100:Oxygen