The overall objective of the research proposed is to determine the effect of nutritional and therapeutic factors on oxygen-induced injury in the lung of the newborn. The nutritional and therapeutic factors to be examined include various forms of lipids and iron, deferoxamine and allopurinol. These treatments were selected on the basis of their current clinical use in newborn infants (lipids, iron) and biochemical rationale regarding free radical formation (deferoxamine, allopurinol). Other studies will examine whether acute hypoxic ischemia may aggravate oxygen-induced lung injury as a consequence of """"""""priming"""""""" oxidative reactions. The lung of newborn animals and mammalian cells in culture will be the focus of the proposed research. Oxygen-induced lung injury will be assessed by quantitative assessment of selected morphologic, biochemical, and physiological parameters. Experiments are included to answer specific questions regarding the pathways involved in formation of lipid peroxidation products and their diagnostic or prognostic relationship to oxygen-induced lung injury. These studies will help define the therapeutic advantages and risks involved with the use of oxygen, dietary lipids, iron and other selected pharmacologic agents in the newborn infant.
Specific Aims : 1. To determine if diet (lipids, various forms of iron) acute hypoxic ischemia, or selected agents known to modulate free radical reactions (phenolic antioxidants, deferoxamine, or allopurinol) influence the severity of oxygen-induced injury in the lung of newborn animals. 2. To explore the prognostic and diagnostic relationships between the amount of specific lipid peroxidation products formed and the extent of oxygen-induced lung injury in newborn animals. 3. To explore the pathways involved in the formation of various lipid peroxidation products, including the influence of aiet (lipids, iron) and selected pharmacologic agents (cyclo-oxygenase and lipoxygenase inhibitors, deferoxamine allopurinol, and phenolic antioxidants) in newborn rabbits and mammalian cell cultures.
