How urine analysis reflects oxidative stress — nitrotyrosine as a potential marker

• Published in: Clinica chimica acta Vol. 297; no. 1; pp. 207 - 216
• Main Authors: Schwemmer, M, Fink, B, Köckerbauer, R, Bassenge, E
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2000
• Subjects: Adult; Ascorbic Acid - administration & dosage; Biomarkers - urine; Chromatography, Gas; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Nitration; Nitroglycerin - administration & dosage; Oxidative Stress; Reactive nitrogen species; Reactive oxygen species; Reference Values; Superoxide dismutase; Tyrosine - analogs & derivatives; Tyrosine - urine; Urinalysis; Nitration; Superoxide dismutase; Reactive oxygen species; Reactive nitrogen species
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/S0009-8981(00)00247-3

Enhanced oxidant stress involved in the pathogenesis of cardiovascular (heart failure, atherosclerosis, ischemia–reperfusion injury), neurodegenerative (M. Alzheimer), metabolic (hypercholesterolemia, diabetes) and inflammatory disorders is mimicked by non-intermittent therapy with nitrovasodilators. We used this latter therapy model to study urinary 3-nitrotyrosine (n-tyr) excretion as a potential biomarker that may reflect the enhanced generation of reactive oxygen species. Namely, free or protein-bound n-tyr is formed in the organism by nitration of tyrosine (residues) via peroxynitrite (reaction product of NO⋅ and O
2
-⋅). Free n-tyr content was analyzed by gas chromatography in urine obtained from healthy human subjects under a nitrite-limited diet during a two-day non-intermittent transdermal administration of glyceroltrinitrate (GTN; 0.4 mg/h) with or without vitamin C (Vit-C; 55 μg/kg/min) as antioxidant. Concomitant with the development of complete vascular tolerance (loss of dilator action), a progressive increase in urinary n-tyr excretion (up to 186±9 μg/day) was demonstrated in volunteers given GTN only. In contrast, when Vit-C was added, the GTN-induced increases in urinary n-tyr content were significantly suppressed (up to 130.20±6.91 μg/day), whereas Vit-C alone even decreased urinary n-tyr content (down to 34.00±5.66 μg/day), which was below control values (56.0±3.4 μg/day). Thus, urinary n-tyr may serve as a biomarker to detect changes in oxidant stress and thereby to evaluate the efficacy of therapeutic interventions aimed at reducing oxidant stress under various pathophysiological conditions.