Body nitrosation potential measured by a novel 15N breath test

Abstract

Oxygenated nitrogen species, for example, the protonated form of nitrous acid (H 2ONO +), dinitrogentrioxide (N 2O 3), dinitrogentetroxide (N 2O 4 ), or peroxynitrite (ONOO −), can react with amines to form molecular nitrogen. These reactions can occur spontaneously with primary aliphatic amines or via cytochrome P450 catalysed reactions with secondary amines. In principle measurements of the excretion of the molecular nitrogen generated by these reactions could be used as an index of the levels of oxygenated nitrogen compounds acting as nitrosating agents. To test this idea, [ 15N 2]urea (3 mmol) was administered orally to five patients infected with Helicobacter pylori (as diagnosed by the [ 13C]urea breath test) and to four healthy volunteers. All participants ingested 3-mmol sodium nitrate as a precursor for NA 5 min before the ingestion of the nitrogen tracer. During the test the participants breathed 100% oxygen to increase the sensitivity of detection of endogenous molecular nitrogen. After the administration of [ 15N 2]urea, the patients with H. pylori showed significantly increased 15N enrichments of exhaled N 2, expressed as δ value (‰), compared with healthy volunteers (patients: 3.5 ± 0.9 vs. volunteers: 1.3 ± 0.4; p < .05). We speculate that the endogenous production of molecular nitrogen is a protective process controlling the body NO and nitrite levels. The 15N breath technique allows the noninvasive estimation of the body nitrosation and could indicate the health risk, possibly the oxidative stress status, caused by highly reactive oxygenated nitrogen species and carbenium ion intermediates.