3-nitrotyrosine and Metabolic-Diseases

Glycation, oxidation, nitration, and crosslinking of proteins are implicated in the pathogenic mechanisms of type 2 diabetes, cardiovascular disease, and chronic kidney disease. Related modified amino acids formed by proteolysis are excreted in urine. We quantified urinary levels of these metabolites and branched-chain amino acids (BCAAs) in healthy subjects and assessed changes in early-stage decline in metabolic, vascular, and renal health and explored their diagnostic utility for a noninvasive health screen. We recruited 200 human subjects with early-stage health decline and healthy controls. Urinary amino acid metabolites were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Machine learning was applied to optimise and validate algorithms to discriminate between study groups for potential diagnostic utility. Urinary analyte changes were as follows: impaired metabolic health-increased N

Topics: Adult; Algorithms; Amino Acids, Branched-Chain; Biomarkers; Body Mass Index; Case-Control Studies; Chromatography, High Pressure Liquid; Female; Glycation End Products, Advanced; Glycosylation; Humans; Kidney; Lysine; Male; Metabolic Diseases; Oxidation-Reduction; Severity of Illness Index; Tandem Mass Spectrometry; Tyrosine; Vascular Diseases

To investigate the effect of termination of galactose feeding after a very short duration of experimental galactosemia on the biochemical abnormalities that are postulated to contribute to the development of retinopathy.. Experimentally galactosemic rats (normal rats fed a 30% galactose-rich diet for 2 months) were fed a galactose-free diet for an additional 1 month. At the end of 3 months, retinas were removed to measure oxidative stress, nitric oxides (NOs), activity of PKC, and levels of nitrotyrosine. Data were compared between rats in the control group (fed a normal diet) and those in the experimentally galactosemic group (30% galactose diet for the entire 3 months).. Interruption of 2 months of galactose feeding by withdrawal of galactose from the diet for 1 additional month had partially beneficial effects on retinal lipid peroxides, but the levels of an endogenous antioxidant, reduced glutathione (GSH), remained subnormal in the retina of galactose-withdrawal rats (P < 0.05 vs. normal and P > 0.05 vs. galactose group). Cessation of the galactose-rich diet had partially beneficial effects on NO levels in the retina, but the levels of nitrotyrosine, an indicator of the formation of peroxynitrite, and activation of PKC were not affected.. The results show that retinal dysmetabolism continues to progress after experimental galactosemia is terminated in rats: Particularly, antioxidant levels remain subnormal, and nitrotyrosine levels are elevated for at least 1 month. Identification of metabolic abnormalities associated with the progression of incipient retinopathy after hyperglycemia is normalized may help in the search for the cause of retinopathy.

Topics: Animals; Disease Progression; Drug Administration Schedule; Galactose; Galactosemias; Glutathione; Hexoses; Lipid Peroxides; Male; Metabolic Diseases; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxidative Stress; Protein Kinase C; Rats; Rats, Sprague-Dawley; Retina; Retinal Diseases; Tyrosine