Urinary Excretion of the Nitrotyrosine Metabolite 3-nitro-4-hydroxyphenylacetic Acid in Preterm and Term Infants

Neonatology. 2008;93(2):73-6. doi: 10.1159/000106783. Epub 2007 Aug 6.


Background: Newborn infants are exposed to various sources of oxidative and/or nitrative stress, which refers to either oxidation and/or nitration of endogenous proteins including loss of their original function. Nitrative stress is predominantly caused following synthesis of peroxynitrite. Particularly preterm infants with immature defense mechanisms against free radical injury appear at risk.

Objective: To test the feasibility of quantifying the degradation products of the peroxynitrite marker nitrotyrosine [3-nitro-4-hydroxyphenylacetic acid (NHPA) and para-hydroxyphenylacetic acid (PHPA)] in neonatal urine samples.

Methods: NHPA and PHPA were determined by gas chromatography/mass spectroscopy in urinary samples of preterm and term infants (mean gestational age = 28.4 and 39.6 weeks, respectively).

Results: The urinary NHPA levels were lower in preterm infants in comparison with term infants. When the NHPA levels were adjusted to the urinary PHPA levels, no differences were found between the two groups.

Conclusions: Nitrotyrosine can be quantified in urinary samples of even the most immature infants. Nitration of endogenous PHPA in the gastrointestinal tract of term infants may have masked potentially higher levels of NHPA in preterm infants.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Free Radicals / metabolism
  • Gastrointestinal Tract / metabolism
  • Gestational Age
  • Humans
  • Infant, Newborn / urine*
  • Infant, Premature / urine*
  • Nitrophenols / urine*
  • Oxidative Stress / physiology
  • Oxygen / metabolism
  • Phenylacetates / urine
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism


  • Free Radicals
  • Nitrophenols
  • Phenylacetates
  • 4-hydroxy-5-nitrophenyl acetic acid
  • 3-nitrotyrosine
  • 4-hydroxyphenylacetic acid
  • Tyrosine
  • Oxygen