Uridine--an indicator of post-exercise uric acid concentration and blood pressure.

Studies have shown that uridine concentration in plasma may be an indicator of uric acid production in patients with gout. It has been also postulated that uridine takes part in blood pressure regulation. Since physical exercise is an effective tool in treatment and prevention of cardio-vascular diseases that are often accompanied by hyperuricemia and hypertension, it seemed advisable to attempt to evaluate the relationship between oxypurine concentrations (Hyp, Xan and UA) and that of Urd and BP after physical exercise in healthy subjects. Sixty healthy men (17.2+/-1.71 years, BMI 23.2+/-2.31 kg m(-2), VO(2max) 54.7+/-6.48 ml kg(-1) min(-1)) took part in the study. The subjects performed a single maximal physical exercise on a bicycle ergometer. Blood for analyses was sampled three times: immediately before exercise, immediately after exercise, and in the 30th min of rest. Concentrations of uridine and hypoxanthine, xanthine and uric acid were determined in whole blood using high-performance liquid chromatography. We have shown in this study that the maximal exercise-induced increase of uridine concentration correlates with the post-exercise increase of uric acid concentration and systolic blood pressure. The results of our study show a relationship between uridine concentration in blood and uric acid concentration and blood pressure. We have been the first to demonstrate that a maximal exercise-induced increase in uridine concentration is correlated with the post-exercise and recovery-continued increase of uric acid concentration in healthy subjects. Thus, it appears that uridine may be an indicator of post-exercise hyperuricemia and blood pressure.

Insulin resistance induced by maximal exercise correlates with a post-exercise increase in uridine concentration in the blood of healthy young men.

Uridine is postulated to participate in the development of insulin resistance. Since exercise is an effective tool in the treatment of insulin resistance it appeared justified to assess the impact of maximal exercise on plasma uridine and insulin sensitivity indices (e.g. insulin and HOMA-IR) in healthy subjects. The study included forty-four healthy males (18.5+/-2.92 years, VO2max 50.2+/-6.26 ml kg⁻¹ min⁻¹). Subjects performed a single maximal exercise on a bicycle ergometer. Blood samples were taken three times: immediately before exercise, immediately after exercise and at the 30(th) min of rest. Uridine concentrations were determined in the whole blood using high-performance liquid chromatography. Serum insulin levels were measured by a specific ELISA method. Insulin sensitivity was assessed by homeostasis model assessment method (HOMA-IR). A maximal exercise-induced increase in the concentration of uridine correlated with post-exercise increases in insulin levels and HOMA-IR. Our results indicate a relationship between the concentration of uridine in the blood and indicators of insulin sensitivity in healthy subjects. We are the first to demonstrate that a maximal exercise-induced increase in the concentration of uridine is correlated with post-exercise increases in insulin levels and HOMA-IR in healthy subjects. It appears that uridine may be an indicator of insulin resistance.

Uridine correlates with the concentration of fructosamine and HbA1c in children with type 1 diabetes.

AIM: Treating uridine as a product of UTP degradation and hypoxanthine as a degradation product of ATP, we assessed the concentration of uridine and hypoxanthine in the blood of children with newly diagnosed type 1 diabetes. We also sought to define the relationship between indicators of the degree of metabolic control of diabetes (fructosamine, HbA1c) and the concentration of the tested catabolites. METHODS: This study was carried out on 33 children aged 12.26 ± 4.49 with newly diagnosed type 1 diabetes during their first hospitalization. The concentration of uridine and hypoxanthine was determined by high-performance liquid chromatography (HPLC). RESULTS: The results showed significantly elevated levels of hypoxanthine and uridine in the blood. We further show that blood uridine level is associated with purine metabolism and hyperglycaemia, and we demonstrate a significant positive correlation between the concentration of uridine and (i) the percentage of HbA1c and (ii) fructosamine levels, which indicate the role of hyperglycaemia in the pathogenesis of pyrimidine nucleotide metabolism in type 1 diabetes prior to diagnosis. CONCLUSION: The results confirm the existence of a relationship between the degree of metabolic control of diabetes and pyrimidine metabolism. Presumably, the analysis of uridine could be used as an adjunct marker of the severity of diabetic complications in newly diagnosed patients.

Adenine, guanine and pyridine nucleotides in blood during physical exercise and restitution in healthy subjects.

Maximal physical exertion is accompanied by increased degradation of purine nucleotides in muscles with the products of purine catabolism accumulating in the plasma. Thanks to membrane transporters, these products remain in an equilibrium between the plasma and red blood cells where they may serve as substrates in salvage reactions, contributing to an increase in the concentrations of purine nucleotides. In this study, we measured the concentrations of adenine nucleotides (ATP, ADP, AMP), inosine nucleotides (IMP), guanine nucleotides (GTP, GDP, GMP), and also pyridine nucleotides (NAD, NADP) in red blood cells immediately after standardized physical effort with increasing intensity, and at the 30th min of rest. We also examined the effect of muscular exercise on adenylate (guanylate) energy charge--AEC (GEC), and on the concentration of nucleosides (guanosine, inosine, adenosine) and hypoxanthine. We have shown in this study that a standardized physical exercise with increasing intensity leads to an increase in IMP concentration in red blood cells immediately after the exercise, which with a significant increase in Hyp concentration in the blood suggests that Hyp was included in the IMP pool. Restitution is accompanied by an increase in the ATP/ADP and ADP/AMP ratios, which indicates an increase in the phosphorylation of AMP and ADP to ATP. Physical effort applied in this study did not lead to changes in the concentrations of guanine and pyridine nucleotides in red blood cells.

Blood glutathione status and activity of glutathione-metabolizing antioxidant enzymes in erythrocytes of young trotters in basic training.

The aim of this study was to evaluate response of blood glutathione status and activity of glutathione-metabolizing antioxidant enzymes in erythrocytes of young trotters in basic training. Nine untrained trotters (aged 16-20 months) were exposed to a 4-month training program based on exercises at low-to-moderate intensity. The conditioning consisted of breaking the horses and running them on distances varying from 4 to 40 km a week. The workloads were increased on a 3-week basis. Exercise intensity was monitored by measuring heart rate and blood lactate. Blood samples were collected at rest, before (RES0) and after (RESt) the conditioning period; moreover, on the latter occasion (on day 112 of training), the blood was also taken immediately after the routine exercise (EXE0) and 60 min thereafter (EXE60). The whole blood samples were analysed for the concentration of reduced, oxidized and total glutathione (GSH, GSSG and TGSH, respectively), while the activities of glutathione peroxidase (GPX) and glutathione-disulfide reductase (GR) were determined in haemolysates. Additionally, the erythrocytic concentrations of oxidized nicotinamide adenine dinucleotide (NAD(+)) and its phosphate (NADP(+)) were measured. All investigated parameters except NAD(+) and reduced/oxidized glutathione ratio (GSH/GSSG) changed during the training period. Following the effortm GPX, NADP(+) and GSH/GSSG were significantly lower (p < 0.05, p < 0.01, p < 0.001, respectively) while GSSG was markedly higher than at rest (RESt). The drop in NADP(+), low GSH/GSSG and high GSSG concentration were sustained at EXE60. Glutathione-disulfide reductase activity was higher after the workout but only at EXE60 the increase in activity was significant. Despite the activities of the GSH-GSSG cycle, enzymes were considerably higher after the training period, the elevated concentration of GSSG and significantly lower GSH/GSSG ratio in the post-exercise measurements suggest that production of reactive oxygen species possibly exceeds the capacity of antioxidative defenses of immature trotters. A more balanced diet with additional antioxidant supplementation and a revision of the basic training protocol used herein are advised.

The purine metabolism of human erythrocytes.

This review summarizes currently available information about a crucial part of erythrocyte metabolism, that is, purine nucleotide conversions and their relationships with other conversion pathways. We describe the cellular resynthesis, interconversion, and degradation of purine compounds, and also the regulatory mechanisms in the conversion pathways. We also mention purine metabolism disorders and their clinical consequences. The literature is fragmentary because studies have concentrated only on selected aspects of purine metabolism; hence the need for a synthetic approach.

Purine nucleotides and their metabolites in erythrocytes of streptozotocin diabetic rats.

OBJECTIVES: In the present study it was tried to obtain a complete overview of purine nucleotide metabolism in erythrocytes of streptozotocin (STZ) induced diabetes mellitus rats. METHODS: Erythrocyte levels of the main nucleotides (ATP, ADP, AMP, GTP, GDP, GMP, IMP, NAD+, NADP+), nucleosides (Ado, Guo, Ino) and the base Hyp were measured using the HPLC method. The parameters that can be deduced from their concentrations: TAN, TGN and AEC, GEC expressed by the ratio of high/low energy nucleoside phosphates were calculated. The effects of streptozotocin-induced diabetes on the concentration and metabolism of rat erythrocyte purine and pyridine nucleotides and the activity of Na+, K+-ATPase as well as Ca2+-ATPase were investigated. RESULTS: Increased dephosphorylation of adenine nucleotides (found as the increased concentration of Ado and Hyp and the decrease in AEC value) and the decrease in ATP and TAN and the changes in the concentrations of NAD+ and NADP+ suggest serious purine and pyridine metabolism disruptions in diabetic erythrocytes and decrease in ATPases activity. CONCLUSION: The observations suggest that purine nucleotide degradation is markedly accelerated in erythrocytes of STZ diabetic rats.