S100B Protein but Not 3-Nitrotyrosine Positively Correlates with Plasma Ammonia in Patients with Inherited Hyperammonemias: A New Promising Diagnostic Tool?

• Published in: Journal of clinical medicine Vol. 12; no. 6; p. 2411
• Main Authors: Czarnecka, Anna Maria, Obara-Michlewska, Marta, Wesół-Kucharska, Dorota, Greczan, Milena, Kaczor, Magdalena, Książyk, Janusz, Rokicki, Dariusz, Zielińska, Magdalena
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.03.2023; MDPI
• Subjects: Amino acids; Ammonia; Biological markers; Biomarkers; Blood; Calcium-binding proteins; Chemokines; Clinical medicine; Congenital diseases; Cytokines; Diagnosis; Enzymes; Health aspects; Hyperammonemia; Measurement; Medical examination; Medical research; Medicine, Experimental; Metabolism; Metabolites; Mutation; Neurotoxicity; Nitro compounds; Patients; Plasma; Proteins; Traumatic brain injury; Tumor necrosis factor-TNF; Poland; United States > US; ammonia; 3-nitrotyrosine; S100B; urea cycle disorders
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm12062411

Individuals with inherited hyperammonemias often present developmental and intellectual deficiencies which are likely to be exaggerated by hyperammonemia episodes in long-term outcomes. In order to find a new, systemic marker common to the course of congenital hyperammonemias, we decided to measure the plasma level of S100 calcium-binding protein B (S100B), which is associated with cerebral impairment. Further, we analyzed three mechanistically diverged but linked with oxidative-nitrosative stress biochemical parameters: 3-nitrotyrosine (3-NT), a measure of plasma proteins' nitration; advanced oxidation protein products (AOPP), a measure of protein oxidation; and glutathione peroxidase (GPx) activity, a measure of anti-oxidative enzymatic capacity. The plasma biomarkers listed above were determined for the first time in congenital hyperammonemia. Also, the level of pro- and anti-inflammatory mediators (i.e., IL-12, IL-6, IL-8, TNF-α, IL-1β, and IL-10) and chemokines (IP-10, MCP-1, MIG, and RANTES) were quantified. S100B was positively correlated with plasma ammonia level, while noticeable levels of circulating 3-NT in some of the patients' plasma did not correlate with ammonia concentration. Overall, the linear correlation between ammonia and S100B but not standard oxidative stress-related markers offers a unique perspective for the future identification and monitoring of neurological deficits risk-linked with hyperammonemia episodes in patients with inherited hyperammonemias. The S100B measure may support the development of therapeutic targets and clinical monitoring in these disorders.