Pulmonary antioxidant defenses in the preterm newborn with respiratory distress and bronchopulmonary dysplasia in evolution: implications for antioxidant therapy.
Preterm neonates with respiratory distress are exposed not only to the relative hyperoxia ex utero, but also to life-saving mechanical ventilation with high inspired oxygen (O2) concentrations, which is considered a major risk factor for the development of bronchopulmonary dysplasia, also referred to as chronic lung disease of infancy. O2 toxicity is mediated through reactive oxygen species (ROS). ROS are constantly generated as byproducts of normal cellular metabolism, but their production is increased in various pathological states, and also upon exposure to exogenous oxidants, such as hyperoxia. Antioxidants, either enzymatic or nonenzymatic, protect the lung against the deleterious effects of ROS. Expression of various pulmonary antioxidants is developmentally regulated in many species so that the expression is increased toward term gestation, as if in anticipation of birth into an O2-rich extrauterine environment. Therefore, the lungs of prematurely born infants may be ill-adapted for protection against ROS. While premature birth interrupts normal lung development, the clinical condition necessitating the administration of high inhaled O2 concentrations may lead to permanent impairment of alveolar development. An understanding of the processes involved in lung growth, especially in alveolarization and vascularization, as well as in repair of injured lung tissue, may facilitate development of strategies to enhance these processes.
Asikainen
Tiina M
TM
Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
White
Carl W
CW
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy / Q000503:physiopathology*
D000975:Antioxidants