Biochemical and cellular aspects of pulmonary oxygen toxicity

Abstract

Pulmonary oxgen toxicity results in intraalveolar hemorrhage and edema following the breakdown of the alveolar-capillary barrier. Hyperoxia causes increased production of partially reduced species of oxygen in lung cells critical for maintaining the integrity of the alveolar-capillary barrier, the capillary endothelial cell and the alveolar epithelium. $\text{In}$ $\text{vitro}$ studies of subcellular organelles isolated from lung including mitochondria, microsomes and nuclei show that oxygen radical production by these organelles increases as a function of oxygen tension. Morphological alterations of lung cell organelles in early stages of oxygen toxicity probably reflect cell injury induced by toxic reactions of relatively high local concentrations of reactive oxygen species. Cell injury and secondary inflammatory responses will occur when edogenous antioxidant defenses are overwhelmed. Oxygen-injured lung cells release paracrine mediators which effect the growth and differentiation of other lung cells. A number of factors can modify pulmonary oxygen toxicity, including the maturational state of the lung, infiltration of phagocytic cells, liposome-mediated augmentation of lung cell antioxidant enzyme activities and commonly prescribed medications.