Peroxynitrite, formed from the reaction of endogenous nitric oxide (NO) with superoxide, is a potent oxidant capable of catalyzing membrane lipid peroxidation, damaging proteins, and oxidizing DNA bases. Recent data indicate that levels of nitrotyrosine (NT), the major product of the reaction of peroxynitrite with proteins, can be used as an index of peroxynitrite formation in vivo.
We measured NT levels in premature infants with and without bronchopulmonary dysplasia (BPD), to assess the degree of peroxynitrite mediated oxidant stress in this disease. NT levels were determined by solid phase immunoradiochemical assay. Four infants (26-28 weeks gestation) who developed BPD (2 were ventilated at 28 days, 2 were extubated but on 40-70% oxygen) were studied between birth and 28 days of life. NT levels were initially undetectable, but increased over time to 1.0 to 1.3 ng/mg protein by 28 days (Figure). Four infants (28-30 weeks gestation) with respiratory distress syndrome, but who had no lung disease at 28 days of life, had serial NT levels that remained less than 0.25 ng/mg protein. Three comparison infants, 30 to 31 weeks gestation, never requiring oxygen, had no detectable NT levels between birth and 28 days.
Two additional premature infants with severe BPD, who remain ventilator dependent at over one year of age, had serial NT levels measured between 6 months of age and one year. Both had elevated NT levels (Patient 1: 0.13-0.76 ng/mg protein, Patient 2: 0.06-0.41 ng/mg protein) while ventilator dependent; levels declined as they began to tolerate weaning of the ventilator. Another infant who died of BPD at 6 months of age had a markedly elevated NT level(5.06 ng/mg protein) shortly before his death.
Conclusion: NT levels, a marker of peroxynitrite formation, appear to be elevated in infants with BPD. This suggests that endogenous NO derived oxidant stress may contribute to the lung injury seen in this disease.
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Banks, B., McClelland, M., Ischiropoulos, H. et al. PLASMA NITROTYROSINE AS AN INDICATOR OF NITRIC OXIDE DERIVED OXIDANT STRESS IN INFANTS WITH BRONCHOPULMONARY DYSPLASIA. † 1935. Pediatr Res 39, 325 (1996) doi:10.1203/00006450-199604001-01959
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