scholarly journals Alcohol abuse is associated with enhanced pulmonary and systemic xanthine oxidoreductase activity

2017 ◽  
Vol 313 (6) ◽  
pp. L1047-L1057 ◽  
Author(s):  
Mehdi A. Fini ◽  
Jeanette Gaydos ◽  
Alicia McNally ◽  
Vijaya Karoor ◽  
Ellen L. Burnham
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Nlrp3 Inflammasome ◽  
Human Subjects ◽  
Xanthine Oxidoreductase ◽  
Healthy Human ◽  
Oxidoreductase Activity ◽  
Pyrin Domain ◽  
Molecular Pattern ◽  
Cox 2

Acute respiratory distress syndrome (ARDS) is a common and devastating disorder. Alcohol use disorders (AUDs) increase ARDS risk and worsen outcomes through mechanisms that may include enhancement of pulmonary oxidative stress. Alcohol consumption increases activity of the enzyme xanthine oxidoreductase (XOR) that contributes to production of both reactive oxygen species (ROS) and uric acid, a damage-associated molecular pattern. These by-products have the potential to modulate proinflammatory pathways, such as those involving cyclooxygenase (COX)-2, and to activate the nucleotide-binding domain, leucine-rich-containing family, pyrin-domain containing-3 (NLRP3) inflammasome. We sought to determine if pulmonary and systemic XOR activity was altered by AUDs. Bronchoscopy with bronchoalveolar lavage (BAL) and blood sampling was performed in otherwise healthy human subjects with AUDs and controls. Uric acid in epithelial-lining fluid, derived from BAL, was substantially higher among individuals with AUDs and did not normalize after 7 days of abstinence; serum uric acid did not differ across groups. XOR enzyme activity in fresh BAL cells and serum was significantly increased in subjects with AUDs. XOR protein in BAL cells from AUD subjects was increased in parallel with COX-2 expression, and furthermore, mRNA expression of NLRP3 inflammasome components was sustained in LPS-stimulated BAL cells from AUD subjects in conjunction with increased IL-1β. Our data suggest that AUDs augment pulmonary and systemic XOR activity that may contribute to ROS and uric acid generation, promoting inflammation. Further investigations will be necessary to determine if XOR inhibition can mitigate alcohol-associated pulmonary oxidative stress, diminish inflammation, and improve ARDS outcomes.

scholarly journals Metformin Corrects Glucose Metabolism Reprogramming and NLRP3 Inflammasome-Induced Pyroptosis via Inhibiting the TLR4/NF-κB/PFKFB3 Signaling in Trophoblasts: Implication for a Potential Therapy of Preeclampsia

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Yang Zhang ◽  
Weifang Liu ◽  
Yanqi Zhong ◽  
Qi Li ◽  
Mengying Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nlrp3 Inflammasome ◽  
Low Dose ◽  
Therapeutic Potential ◽  
Metabolic Phenotypes ◽  
Pyrin Domain ◽  
Underlying Mechanisms ◽  
And Oxidative Stress ◽  
Receptor Family

NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome-mediated pyroptosis is a crucial event in the preeclamptic pathogenesis, tightly linked with the uteroplacental TLR4/NF-κB signaling. Trophoblastic glycometabolism reprogramming has now been noticed in the preeclampsia pathogenesis, plausibly modulated by the TLR4/NF-κB signaling as well. Intriguingly, cellular pyroptosis and metabolic phenotypes may be inextricably linked and interacted. Metformin (MET), a widely accepted NF-κB signaling inhibitor, may have therapeutic potential in preeclampsia while the underlying mechanisms remain unclear. Herein, we investigated the role of MET on trophoblastic pyroptosis and its relevant metabolism reprogramming. The safety of pharmacologic MET concentration to trophoblasts was verified at first, which had no adverse effects on trophoblastic viability. Pharmacological MET concentration suppressed NLRP3 inflammasome-induced pyroptosis partly through inhibiting the TLR4/NF-κB signaling in preeclamptic trophoblast models induced via low-dose lipopolysaccharide. Besides, MET corrected the glycometabolic reprogramming and oxidative stress partly via suppressing the TLR4/NF-κB signaling and blocking transcription factor NF-κB1 binding on the promoter PFKFB3, a potent glycolytic accelerator. Furthermore, PFKFB3 can also enhance the NF-κB signaling, reduce NLRP3 ubiquitination, and aggravate pyroptosis. However, MET suppressed pyroptosis partly via inhibiting PFKFB3 as well. These results provided that the TLR4/NF-κB/PFKFB3 pathway may be a novel link between metabolism reprogramming and NLRP3 inflammasome-induced pyroptosis in trophoblasts. Further, MET alleviates the NLRP3 inflammasome-induced pyroptosis, which partly relies on the regulation of TLR4/NF-κB/PFKFB3-dependent glycometabolism reprogramming and redox disorders. Hence, our results provide novel insights into the pathogenesis of preeclampsia and propose MET as a potential therapy.

scholarly journals Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults

2019 ◽  
Vol 244 (3) ◽  
pp. 272-278
Author(s):  
Flora S Park ◽  
Victoria L Kay ◽  
Justin D Sprick ◽  
Alexander J Rosenberg ◽  
Garen K Anderson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Negative Pressure ◽  
Lower Body Negative Pressure ◽  
Human Subjects ◽  
Oxidative Stress Response ◽  
Lower Body ◽  
Healthy Human ◽  
Healthy Human Subjects ◽  
Simulated Hemorrhage

Hemorrhage is a leading cause of potentially preventable death in both civilian and military trauma settings. Lower body negative pressure (LBNP) is a validated, non-invasive, and reproducible approach to simulate hemorrhage by inducing central hypovolemia in healthy conscious humans. The oxidative stress response to simulated hemorrhage via LBNP has not been quantified. We hypothesized that systemic markers of oxidative stress would increase with application of maximal, pre-syncopal limited LBNP. Fifteen healthy human subjects (11 M/4 F; age 27 ± 1 y) were recruited for a single LBNP experiment to presyncope (chamber pressure was progressively reduced every 5-min in a stepwise manner). Heart rate was assessed via ECG, arterial pressure and stroke volume (SV) were measured continuously via finger photoplethysmography, muscle oxygen saturation (SmO2) was measured via near-infrared spectroscopy, and venous blood samples were collected at baseline and presyncope. Plasma samples were analyzed for F2-isoprostanes (F2-IsoP), a global marker of oxidative stress. The magnitude of central hypovolemia, indexed by the maximal decrease (%Δ) in SV, ranged from 27 to 74% (53.5 ± 3.9%; P < 0.001), and mean arterial pressure (MAP) decreased by 12.6 ± 2.6% ( P < 0.001 vs. pre-LBNP baseline). F2-IsoP increased by 28.5 ± 11.6% ( P = 0.05) from baseline (24 ± 2 pg/mL) to presyncope (29 ± 3 pg/mL). The increase in F2-IsoP was not associated with %Δ SV ( r = 0.21, P = 0.46), %Δ MAP ( r = 0.05, P = 0.86), %Δ SmO2 ( r = 0.05, P = 0.90), or the maximum level of LBNP attained ( r = 0.35, P = 0.20). Simulated hemorrhage induced by LBNP to presyncope elicited an increase in oxidative stress, but this response was not associated with the magnitude of central hypovolemia, hypotension, or the decrease in peripheral muscle tissue oxygen saturation. These findings have important implications for the study of hemorrhage using LBNP, and future investigations of interventions targeting oxidative stress. Impact statement We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F2-isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.

Oxidative stress to human lymphocytes by xanthine oxidoreductase activity

2001 ◽  
Vol 35 (6) ◽  
pp. 665-679 ◽  
Author(s):  
Maria Giulia Battelli ◽  
Silvia Musiani ◽  
Pier Luigi Tazzari ◽  
Fiorenzo Stirpe
Keyword(s):  
Oxidative Stress ◽  
Human Lymphocytes ◽  
Xanthine Oxidoreductase ◽  
Oxidoreductase Activity

scholarly journals Effect of NADH on hypoxanthine hydroxylation by native NAD+-dependent xanthine oxidoreductase of rat liver, and the possible biological role of this effect

1981 ◽  
Vol 200 (3) ◽  
pp. 597-603 ◽  
Author(s):  
Z W Kamiński ◽  
M M Jezewska
Keyword(s):  
Uric Acid ◽  
Rat Liver ◽  
Time Course ◽  
De Novo ◽  
Xanthine Oxidoreductase ◽  
Reaction Sequence ◽  
Oxidoreductase Activity ◽  
Dependent Activity ◽  
Sepharose 4B

The course of the reaction sequence hypoxanthine leads to xanthine leads to uric acid, catalysed by the NAD+-dependent activity of xanthine oxidoreductase, was investigated under conditions either of immediate oxidation of the NADH formed or of NADH accumulation. The enzymic preparation was obtained from rat liver, and purified 75-fold (as compared with the 25000 g supernatant) on a 5′-AMP-Sepharose 4B column; in this preparation the NAD+-dependent activity accounted for 100% of total xanthine oxidoreductase activity. A spectrophotometric method was developed for continuous measurements of changes in the concentrations of the three purines involved. The time course as well as the effects of the concentrations of enzyme and of hypoxanthine were examined. NADH produced by the enzyme lowered its activity by 50%, resulting in xanthine accumulation and in decreases of uric acid formation and of hypoxanthine utilization. The inhibition of the Xanthine oxidoreductase NAD+-dependent activity by NADH is discussed as a possible factor in the regulation of IMP biosynthesis by the ‘de novo’ pathway or (from unchanged hypoxanthine) by ther salvage pathway.

scholarly journals Xanthine oxidoreductase activity is associated with serum uric acid and glycemic control in hemodialysis patients

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Ayumi Nakatani ◽  
Shinya Nakatani ◽  
Eiji Ishimura ◽  
Takayo Murase ◽  
Takashi Nakamura ◽  
...  
Keyword(s):  
Uric Acid ◽  
Glycemic Control ◽  
Serum Uric Acid ◽  
Hemodialysis Patients ◽  
Xanthine Oxidoreductase ◽  
Oxidoreductase Activity

scholarly journals The effects of allopurinol, uric acid, and inosine administration on xanthine oxidoreductase activity and uric acid concentrations in broilers

2012 ◽  
Vol 91 (11) ◽  
pp. 2895-2903 ◽  
Author(s):  
T. Settle ◽  
M.D. Carro ◽  
E. Falkenstein ◽  
W. Radke ◽  
H. Klandorf
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidoreductase ◽  
Oxidoreductase Activity

Processed Tomato Products as a Source of Dietary Lycopene: Bioavailability and Antioxidant Properties

2004 ◽  
Vol 65 (4) ◽  
pp. 161-165 ◽  
Author(s):  
A. Venket Rao
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Human Subjects ◽  
Antioxidant Properties ◽  
Healthy Human ◽  
Increased Risk ◽  
Total Antioxidant ◽  
Trolox Equivalent ◽  
Tomato Products ◽  
Total Antioxidant Potential

Oxidative stress is one of the major contributors to increased risk of chronic diseases. A diet rich in tomatoes and tomato products containing lycopene, a carotenoid antioxidant, has been found to protect against these chronic diseases by mitigating oxidative damage. The study aim was to evaluate the effects of a long-term tomato-rich diet, consisting of various processed tomato products, on bioavailability and antioxidant properties of lycopene. Seventeen healthy human subjects (ten men, seven non-pregnant women) participated in the study. Following a two-week washout period during which subjects avoided foods containing lycopene, all subjects consumed test tomato products including tomato juice, tomato sauce, tomato paste, ketchup, spaghetti sauce, and ready-to-serve tomato soup providing 30 mg of lycopene a day for four weeks. At the end of treatment, serum lycopene level increased significantly (p <0.05), from 181.79 ± 31.25 to 684.7 ± 113.91 nmol/L. Similarly, total antioxidant potential increased significantly (p <0.05), from 2.26 ± 0.015 to 2.38 ± 0.17 mmol/L Trolox equivalent. Lipid and protein oxidation was reduced significantly (p <0.05). The results suggest that a tomato-rich diet containing different sources of lycopene can increase serum lycopene levels and reduce oxidative stress effectively.

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