Hydroxyl Radical Generation in Oxygen-treated Infants

Because the hydroxyl radical is capable of oxidizing phenylalanine to O-tyrosine, we sought to determine whether increased levels of O-tyrosine are found in urine of infants treated with supplemental oxygen. A total of 39 consecutively admitted neonates to an intensive care unit were included. Twenty-seven received supplemental oxygen therapy for respiratory disease, and 12 did not. Urinary O-tyrosine levels were determined on two or more occasions using high-performance liquid chromatography with results expressed as a percentage of the urinary phenylalanine concentration. Using simple and stepwise multiple linear regression analyses, urinary O-tyrosine was examined for associations with relevant clinical conditions and laboratory measurements. Infants supplemented with oxygen showed significantly higher mean +/- SEM urinary O-tyrosine levels (0.40% +/- 0.028) compared with those remaining in room air (0.18% +/- 0.012). Mean daily FIO2 was the clinical and laboratory variable most highly correlated with urinary O-tyrosine (r = 0.66). In the stepwise regression, significant associations were also found for renal fractional sodium excretion and Apgar score at 5 minutes. Hydroxylation at the O position of phenylalanine, a specific direct marker for the hydroxyl radical attack, was strongly associated with oxygen treatment in neonates. This finding increases our understanding of the pathogenesis of oxygen injury and suggests a basis for developing therapeutic approaches.