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Rule of UA on Cardiac Myocytes Uric Acid Differently Influence the Oxidative Damage Induced by Acute Exposure of High Level of Glucose in Chicken Cardiac Myocytes

ABSTRACT: Background: Uric acid (UA) is a potent scavenger of oxidants in mammalian and avian species. In humans, hyperglycemia with simultaneous hyperuricemia may exert additional damage to the cardiovascular system. Chickens naturally have hyperglycemia (10.1–11.0 mmol/L) and hyperuricemia (100–900 ?mol/L), which makes them an interesting model. Methods: The aim of this study was to investigate the effects of UA on the oxidative damage induced by acute exposure of high level of glucose in chicken cardiac myocytes. Results: Cell viability and the concentrations of thiobarbituric acid reactive substance (TBARS) were decreased by glucose treatment in a dose- and time-dependent manner. After acute exposure to high level of glucose (300 mM), a moderate level of UA (300 ?M) increased cell viability and reduced TBARS and glutathione (GSH) content. Compared to the control or to independent high glucose (300 mM) or UA (1,200 ?M) treatment, the concurrent treatment of high glucose and high UA significantly increased the TBARS, protein carbonyl contents, and ROS concentration, whereas it decreased the cell viability, superoxide dismutase (SOD) activity, and GSH content. In the presence of high glucose and UA, the nucleic protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) was decreased and the mRNA levels of the genes cat, sod1, sod2, gss, and gclc were downregulated. Conclusion: In conclusion, acute exposure of high level of glucose induced oxidative damage in the cardiac myocytes of chicken. The present result suggests that an adequate level of uric acid is helpful in alleviating the acute oxidative damage that is induced by high glucose, whereas the inhibition of the Nrf2 pathway by a high level of uric acid may render the cardiac myocytes more vulnerable to suffering from oxidative damage.

SUBMITTER: Sun X

PROVIDER: S-EPMC7785973 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Mechanisms of postoperative delirium remain poorly understood, limiting development of effective treatments. We tested the hypothesis that intraoperative oxidative damage is associated with delirium and neuronal injury and that disruption of the blood-brain barrier modifies these associations. METHODS:In a prespecified cohort study of 400 cardiac surgery patients enrolled in a clinical trial of atorvastatin to reduce kidney injury and delirium, we measured plasma concentrations of F2-isoprostanes and isofurans using gas chromatography-mass spectrometry to quantify oxidative damage, ubiquitin carboxyl-terminal hydrolase isozyme L1 to quantify neuronal injury, and S100 calcium-binding protein B using enzyme-linked immunosorbent assays to quantify blood-brain barrier disruption before, during, and after surgery. We performed the Confusion Assessment Method for the Intensive Care Unit twice daily to diagnose delirium. We measured the independent associations between intraoperative F2-isoprostanes and isofurans and delirium (primary outcome) and postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (secondary outcome), and we assessed if S100 calcium-binding protein B modified these associations. RESULTS:Delirium occurred in 109 of 400 (27.3%) patients for a median (10th, 90th percentile) of 1.0 (0.5, 3.0) days. In the total cohort, plasma ubiquitin carboxyl-terminal hydrolase isozyme L1 concentration was 6.3 ng/ml (2.7, 14.9) at baseline and 12.4 ng/ml (7.9, 31.2) on postoperative day 1. F2-isoprostanes and isofurans increased throughout surgery, and the log-transformed sum of intraoperative F2-isoprostanes and isofurans was independently associated with increased odds of postoperative delirium (odds ratio, 3.70 [95% CI, 1.41 to 9.70]; P = 0.008) and with increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (ratio of geometric means, 1.42 [1.11 to 1.81]; P = 0.005). The association between increased intraoperative F2-isoprostanes and isofurans and increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 was amplified in patients with elevated S100 calcium-binding protein B (P = 0.049). CONCLUSIONS:Intraoperative oxidative damage was associated with increased postoperative delirium and neuronal injury, and the association between oxidative damage and neuronal injury was stronger among patients with increased blood-brain barrier disruption.

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Rule of UA on Cardiac Myocytes Uric Acid Differently Influence the Oxidative Damage Induced by Acute Exposure of High Level of Glucose in Chicken Cardiac Myocytes

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