Hyperoxic injury of immature guinea pig lung is mediated via hydroxyl radicals.
Support of preterm infants with ventilation and oxygen therapy frequently leads to the development of chronic lung disease. Oxidative stress, through the generation of excess oxygen free radicals, is thought to play a major role in this condition. At present the radical species responsible for oxidative lung injury is not known, and effective antioxidant based therapies are not available. The purpose of this study was to determine whether hydroxyl radicals, potent reactive oxygen species, are involved in chronic oxidative lung injury. To obtain this information we developed a animal model of chronic lung injury using the preterm guinea pig and analyzed lung tissue from these pups for o-tyrosine, a specific marker of hydroxyl radical attack. In normoxia control pups the pulmonary content of o-tyrosine was low during the first 4 wk of life (range 0.11-0.12% tyrosine). Pups maintained in 85% oxygen were found to have increasing lung o-tyrosine over this period (d 7, 0.51%; d 14, 0.8%; d 21, 1.28%; d 28, 1.45% tyrosine). From d 21, the nonenzymatic glycosylation end product, N-epsilon-carboxymethyllysine was also present in significantly increased amounts in hyperoxic-exposed pups. These results implicate hydroxyl radicals as a significant oxidizing species in hyperoxic lung injury and provide a basis for understanding collagen deposition in the neonatal lung.
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D017665:Hydroxyl Radical / Q000378:metabolism*; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives / Q000032:analysis; D008297:Male; D018384:Oxidative Stress; D011247:Pregnancy; D015996:Survival Rate; D014443:Tyrosine / Q000032:analysis
D017665:Hydroxyl Radical; D014443:Tyrosine; C048496:N(6)-carboxymethyllysine; D008239:Lysine