LIPID INVOLVEMENT IN OXYGEN TOXICITY

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Toxic oxygen species are implicated in causing lung injury. Evidence that oxy-radicals and other oxygen species are involved is inferential, but based on current understanding of oxygen chemistry in complex biological systems. It is important to understand how toxic oxygen species can cause tissue injury and by what chemical mechanisms they act. In general, we will investigate the role of lipid peroxidation in acute lung injury that results from exposure to conditions in which toxic oxygen species are presumably formed. Since it has not been demonstrated that lipid peroxidation is a necessary step in the mechanisms responsible for lung injury, we propose to determine if lipid peroxidation is an essential event leading to lung damage or only a parallel chemical process. Two model systems will be examined. The first involves lung damage resulting from hyperoxia. The second is a study of lung damage caused by phorbol myristate acetate. We will look for the formation of peroxidation products that can be directly traced to known chemical reactions. We will attempt to determine what chemical species are responsible for the initiation of peroxidation. In this study, we will use gas chromatography-mass spectrometric techniques that will allow us to quantitate minute (picogram) amounts of material.