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Controlled Feeding of an 8-d, High-Dairy Cheese Diet Prevents Sodium-Induced Endothelial Dysfunction in the Cutaneous Microcirculation of Healthy, Older Adults through Reductions in Superoxide.
Alba, BK, Stanhewicz, AE, Dey, P, Bruno, RS, Kenney, WL, Alexander, LM
The Journal of nutrition. 2020;(1):55-63
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Abstract
BACKGROUND While excess dietary sodium impairs vascular function by increasing oxidative stress, the dietary incorporation of dairy foods improves vascular health. We demonstrated that single-meal cheese consumption ameliorates acute, sodium-induced endothelial dysfunction. However, controlled feeding studies examining the inclusion of cheese, a dairy product that contains both bioactive constituents and sodium, are lacking. OBJECTIVES We tested the hypothesis that microcirculatory endothelium-dependent dilation (EDD) would be impaired by a high-sodium diet, but a sodium-matched diet high in dairy cheese would preserve EDD through oxidant stress mechanisms. METHODS We gave 11 adults without salt-sensitive blood pressure (<10 mmHg Δ mean arterial pressure; 64 ± 2 y) 4 separate 8-d controlled dietary interventions in a randomized, crossover design: a low-sodium, no-dairy intervention (LNa; 1500 mg/d sodium); a low-sodium, high-cheese intervention (LNaC; 1500 mg/d sodium, 170 g/d cheese); a high-sodium, no-dairy intervention (HNa; 5500 mg/d sodium); and a high-sodium, high-cheese intervention (HNaC; 5500 mg/d sodium, 170 g/d cheese). On Day 8 of each diet, EDD was assessed through a localized infusion (intradermal microdialysis) of acetylcholine (ACh), both alone and during coinfusion of NG-nitro-L-arginine methyl ester (NO synthase inhibitor), L-ascorbate (nonspecific antioxidant), apocynin [NAD(P)H oxidase inhibitor], or tempol (superoxide scavenger). RESULTS Compared with LNa, microvascular responsiveness to ACh was attenuated during HNa (LNa: -4.82 ± 0.20 versus HNa: -3.21 ± 0.55 M logEC50; P = 0.03) but not LNaC (-5.44 ± 0.20 M logEC50) or HNaC (-4.46 ± 0.50 M logEC50). Further, ascorbate, apocynin, and tempol administration each increased ACh-induced vasodilation during HNa only (Ringer's: 38.9 ± 2.4; ascorbate: 48.0 ± 2.5; tempol: 45.3 ± 2.7; apocynin: 48.5 ± 2.6% maximum cutaneous vascular conductance; all P values < 0.01). CONCLUSIONS These results demonstrate that incorporating dairy cheese into a high-sodium diet preserves EDD by decreasing the concentration of superoxide radicals. Consuming sodium in cheese, rather than in nondairy sources of sodium, may be an effective strategy to reduce cardiovascular disease risk in salt-insensitive, older adults. This trial was registered at clinicaltrials.gov as NCT03376555.
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Bronchodilators modulate inflammation in chronic obstructive pulmonary disease subjects.
Santus, P, Buccellati, C, Centanni, S, Fumagalli, F, Busatto, P, Blasi, F, Sala, A
Pharmacological research. 2012;(4):343-8
Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by neutrophilic airway inflammation and oxidative stress. Leukotriene B₄ (LTB₄), a potent proinflammatory mediator, is synthesized by 5-lipoxygenase (5-LO), which is activated by the presence of lipid hydroperoxides resulting from oxidative stress on biological membranes. We proposed to evaluate the effect of a four week treatment with two different bronchodilators of common practice in COPD treatment, on the production of reactive oxygen species (ROS), in particular superoxide anions, and of LTB₄ by peripheral blood neutrophils obtained from COPD subjects. 24 subjects among the COPD outpatients were enrolled, and randomized to receive either formoterol (12 μg bid) or tiotropium (18 μg od). Peripheral blood neutrophils were obtained at the start and at the end of the treatment, and production of superoxide anions and of LTB₄ were evaluated as previously published. The results obtained showed a decrease in the unstimulated production of superoxide by isolated neutrophils in both groups, but tiotropium only was effective in modulating the production of LTB₄, while formoterol caused an increased production of superoxide in response to fMLP, when compared to values obtained before treatment. In conclusion, tiotropium showed a better antiinflammatory activity profile when compared to formoterol in a clinical setting, reducing superoxide and LTB₄ production by peripheral neutrophils obtained from COPD subjects.
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The use of superoxidized aqueous solution versus saline as a replacement solution in the versajet lavage system in chronic diabetic foot ulcers: a pilot study.
Bowling, FL, Crews, RT, Salgami, E, Armstrong, DG, Boulton, AJ
Journal of the American Podiatric Medical Association. 2011;(2):124-6
Abstract
BACKGROUND The removal of necrotic tissue from chronic wounds is required for wound healing to occur. Hydrodebridement (jet lavage) and superoxidized aqueous solution have been independently used for debriding wounds. We sought to investigate the use of superoxidized aqueous solution with a jet lavage system. METHODS Twenty patients with diabetic foot ulcers were randomly assigned in a 1:1 ratio to receive jet lavage debridement with either superoxidized aqueous solution or standard saline weekly. RESULTS There was no significant difference between the two treatments in the reduction of bacterial load or wound size in 4 weeks. No adverse reactions were reported for either treatment. CONCLUSIONS The use of superoxidized aqueous solution for jet lavage debridement seemed to be as safe and effective as saline. Future investigations should concentrate on whether superoxidized aqueous solution may reduce the bacterial air contamination associated with hydrodebridement.
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Comparative effects of dietary supplementation with red grape juice and vitamin E on production of superoxide by circulating neutrophil NADPH oxidase in hemodialysis patients.
Castilla, P, Dávalos, A, Teruel, JL, Cerrato, F, Fernández-Lucas, M, Merino, JL, Sánchez-Martín, CC, Ortuño, J, Lasunción, MA
The American journal of clinical nutrition. 2008;(4):1053-61
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Abstract
BACKGROUND Atherosclerotic cardiovascular disease is the most common cause of death among hemodialysis patients; it has been attributed to increased oxidative stress, dyslipidemia, malnutrition, and chronic inflammation. Activation of neutrophils is a well-recognized feature in dialysis patients, and superoxide-anion production by neutrophil NADPH oxidase may contribute significantly to oxidative stress. OBJECTIVE The aim of the study was to compare the effects of dietary supplementation with concentrated red grape juice (RGJ), a source of polyphenols, and vitamin E on neutrophil NADPH oxidase activity and other cardiovascular risk factors in hemodialysis patients. DESIGN Thirty-two patients undergoing hemodialysis were recruited and randomly assigned to groups to receive dietary supplementation with RGJ, vitamin E, or both or a control condition without supplementation or placebo. Blood was obtained at baseline and on days 7 and 14 of treatment. RESULTS RGJ consumption but not vitamin E consumption reduced plasma concentrations of total cholesterol and apolipoprotein B and increased those of HDL cholesterol. Both RGJ and vitamin E reduced plasma concentrations of oxidized LDL and ex vivo neutrophil NADPH oxidase activity. These effects were intensified when the supplements were used in combination; in that case, reductions in the inflammatory biomarkers intercellular adhesion molecule 1 and monocyte chemoattractant protein 1 also were observed. CONCLUSIONS Regular ingestion of concentrated RGJ by hemodialysis patients reduces neutrophil NADPH-oxidase activity and plasma concentrations of oxidized LDL and inflammatory biomarkers to a greater extent than does that of vitamin E. This effect of RGJ consumption may favor a reduction in cardiovascular risk.
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Effects of hyperoncotic or hypertonic-hyperoncotic solutions on polymorphonuclear neutrophil count, elastase- and superoxide-anion production: a randomized controlled clinical trial in patients undergoing elective coronary artery bypass grafting.
Molter, GP, Silomon, M, Bauer, C, Ziegeler, S, Soltesz, S
Acta anaesthesiologica Scandinavica. 2007;(7):914-21
Abstract
BACKGROUND Hypertonic-hyperoncotic solutions may be an effective treatment for systemic inflammatory response syndrome (SIRS). With regard to the immunomodulatory effects of these drugs, previous studies demonstrated controversial results. Therefore, the present study investigated the influence of different hyperoncotic and hypertonic-hyperoncotic solutions on polymorphonuclear neutrophil leukocyte (PMNL) count, elastase and superoxide-anion production in patients undergoing elective coronary artery bypass grafting (CABG) with cardiopulmonary bypass. METHODS Fifty patients scheduled for elective CABG with cardiopulmonary bypass were randomly assigned to five groups: (i) NaCl 0.9%, 750 ml/m(2) body surface area (BSA); (ii) hydroxyethylic starch 10%, 250 ml/m(2) BSA and NaCl 0.9%, 400 ml/m(2) BSA; (iii) dextran 10%, 250 ml/m(2) BSA and NaCl 0.9%, 300 ml/m(2) BSA; (iv) hypertonic sodium chloride 7.2%/hyperoncotic hydroxyethylic starch 10%, 150 ml/m(2) BSA; and (v) hypertonic sodium chloride 7.2%/hyperoncotic dextran 10%, 150 ml/m(2) BSA. Blood samples were drawn from arterial, central venous and coronary artery sinus catheters peri-operatively. PMNL count, superoxide-anion production and elastase were recorded. RESULTS PMNL counts and elastase activity increased in all groups after reperfusion. Superoxide-anion production showed only minor changes. Between groups, no significant differences were demonstrated. CONCLUSIONS Infusion of clinically relevant doses of hypertonic-hyperoncotic solution did not affect PMNL count, elastase- or superoxide-anion production during elective CABG with cardiopulmonary bypass.
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Efficacy and safety of neutral pH superoxidised solution in severe diabetic foot infections.
Martínez-De Jesús, FR, Ramos-De la Medina, A, Remes-Troche, JM, Armstrong, DG, Wu, SC, Lázaro Martínez, JL, Beneit-Montesinos, JV
International wound journal. 2007;(4):353-62
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Abstract
The use of antiseptics in wound care is often controversial and there is definitely a need for a non toxic, highly disinfective agent. This study assessed the efficacy of a neutral pH superoxidised aqueous solution (NpHSS) for infection control, odour reduction and surrounding skin and tissue damage on infected diabetic foot ulcerations. From November 2003 to March 2004, 45 patients with type 2 diabetes were randomised into a single-blind clinical trial comparing NpHSS (intervention group; n = 21) versus conventional disinfectant (control group; n = 16). All patients received comprehensive care including surgical debridement as appropriate, moist wound care, intensive glucose control and broad spectrum antibiotics. Treatment groups were matched in terms of sex, age (61.9 +/- 11.9 versus 67.8 +/- 11.6), years of diabetes duration (16.4 +/- 8.1 versus 17 +/- 10.2), obesity, HgAlc (7.1 +/- 2 versus 6.7 +/- 1.8), initial fasting glycaemia (163 +/- 59 versus 152 +/- 65.8 mg/dl), ulcer duration/week (13.7 +/- 24 versus 15.1 +/- 16.3), B/A Index (0.9 +/- 0.5 versus 1.14 +/- 0.7), depth and extent of infection/periwound cellulitis (groups B and C of the Tampico Hospital Classification) as well as aetiology (P = 0.647). Odour reduction was achieved in all NpHSS patients (100% versus 25%; P < 0.01) and surrounding cellulitis diminished (P < 0.001) in 17 patients (80.9% versus 43.7%). Nineteen patients in the NpHSS group showed advancement to granulating tissue stage (90.4% versus 62.5%; P = 0.05) with significantly less tissue toxicity (94% versus 31.2%; P < 0.01). A non toxic, NpHSS, as part of a comprehensive care regimen, may be more efficacious in infection control, odour and erythema reduction than conventional disinfectants in treatment of diabetic foot infections.
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Neutrophil superoxide anion generation during atorvastatin and fluvastatin therapy used in coronary heart disease primary prevention.
Kowalski, J, Barylski, M, Banach, M, Grycewicz, J, Irzmański, R, Pawlicki, L
Journal of cardiovascular pharmacology. 2006;(4):143-7
Abstract
Neutrophil superoxide anion generation was measured during atorvastatin and fluvastatin therapy in patients with coronary heart disease (CHD) risk. The patients were randomly allotted into three groups. The atorvastatin group comprised 17 patients who were administered the drug orally 10 mg a day at bed time. The fluvastatin group consisted of 18 patients on an oral dose of 40 mg once daily at bed time. The control group comprised 12 healthy subjects with no drug administration. Blood samples were collected from cubital vein before and after 6-week therapy with these drugs and once in the control group. Neutrophil superoxide anion generation in whole blood without and with opsonized zymosan (OZ) stimulation was determined using superoxide dismutase from bovine erythrocytes. In the atorvastatin group, statistically significant (P < 0.05) decrease in superoxide anion generation by nonstimulated and OZ-stimulated neutrophils was observed after 6 weeks of therapy. In fluvastatin group, no changes in neutrophil superoxide anion generation were observed after the 6-week treatment period. Our study has shown an additional nonlipid mechanism of atorvastatin used in CHD primary prevention.
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Perioperative treatment with human growth hormone down-regulates apoptosis and increases superoxide production in PMN from patients undergoing infrarenal abdominal aortic aneurysm repair.
Decker, D, Springer, W, Tolba, R, Lauschke, H, Hirner, A, von Ruecker, A
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2005;(3):193-9
Abstract
BACKGROUND Recombinant human growth hormone (hGH) therapy has a beneficial effect on catabolism and wound healing after major surgery. Polymorphonuclear neutrophils (PMN) play an important role in this context. In a prospective, double-blind, randomized, placebo-controlled trial we studied the effect of perioperative hGH treatment on postoperative wound healing and on changes in superoxide generation and susceptibility to apoptosis of PMN in elderly patients undergoing elective abdominal aortic aneurysm repair. METHODS Seven patients were treated with high-dose hGH (16 U/d) for nine days, seven patients with a placebo. IGF-I, neutrophil count, O2-production induced by opsonized zymosan and apoptosis of PMN were measured and correlated with clinical outcome. RESULTS Perioperative hGH treatment more than doubled the O2- production in PMN before and 24 h after surgery (p < 0.01). The long-term capacity of PMN to generate O2 in vitro was prolonged (p < 0.001) in the hGH group. Spontaneous and Fas-inducible apoptosis was strongly down-regulated in PMN after surgery in all patients (p < 0.01). hGH-treatment distinctly reduced apoptosis in PMN before and after surgery (p < 0.01). Clinical outcome was similar in both groups. CONCLUSION Perioperative hGH treatment results in an enhanced O2- production in PMN and in a prolongation of the functional life span of these cells. This may improve immune function and help to overcome the postoperative anergic state of the immune system especially in elderly individuals.
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Enhanced platelet release of superoxide anion in systemic hypertension: role of AT1 receptors.
Germanò, G, Sanguigni, V, Pignatelli, P, Caccese, D, Lenti, L, Ragazzo, M, Lauro, R, Violi, F
Journal of hypertension. 2004;(6):1151-6
Abstract
BACKGROUND Enhanced oxidative stress has been observed in hypertension, but the underlying mechanism has not been fully clarified. OBJECTIVE To study the relationship between oxygen free radicals and hypertension, using platelets as a tool to measure the cellular production of superoxide anion (O2). DESIGN Forty patients with hypertension were allocated randomly to groups to receive either irbesartan, an inhibitor of angiotensin II type 1 (AT1) receptors (n = 20), or a diuretic (hydrochlorothiazide) (n = 20). In each patient, collagen-induced production of O2 by platelets was studied before and after 4 weeks of treatment. Forty sex- and age-matched healthy individuals were studied as controls. METHODS Platelet-produced O2 was measured using lucigenin chemiluminescence and hydroethidine cytofluorimetric analysis. RESULTS Compared with healthy individuals, patients with hypertension showed a greater production of O2 by platelets (P < 0.001); there was no correlation between blood pressure and platelet O2 production. After treatment, no changes in platelet O2 formation were observed in patients receiving hydrochlorothiazide; conversely, those treated with irbesartan showed a significant (P < 0.001) decrease in platelet O2 production. At the end of the treatment, no differences in blood pressures were observed between the two groups. In-vitro incubation of platelets with angiotensin II elicited a significant increase in O2 (P < 0.001) that was dose-dependently inhibited by irbesartan and diphenylene iodonium, an inhibitor of NADPH oxidase. CONCLUSION Patients with hypertension showed an enhanced formation of O2 in platelets that was not dependent on blood pressure but could be mediated by AT1 receptors via NADPH oxidase activation.
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Inspired superoxide anions attenuate blood lactate concentrations in postoperative patients.
Iwama, H, Ohmizo, H, Furuta, S, Ohmori, S, Watanabe, K, Kaneko, T, Tsutsumi, K
Critical care medicine. 2002;(6):1246-9
Abstract
OBJECTIVE Low concentrations of superoxide (O(2)(-)) constitute a portion of atmosphere negative ions in the form of O(2)-(H(2)O)(n), which has been reported to have a stimulatory effect on superoxide dismutase activity. If superoxide dismutase is activated by inspired negative ions containing O(2)(-), aerobic metabolism could be improved. To test this hypothesis, we examined blood lactate concentrations in postoperative patients with or without inhalation of air from a home humidifier that generates O(2)-(H(2)O)(n). DESIGN Prospective, randomized, controlled trial. SETTING Neurosurgical intensive care unit of a general hospital. PATIENTS Twenty postneurosurgical patients with arterial blood lactate concentrations >1.5 mmol/L were studied and were divided randomly into two groups. INTERVENTIONS One group received 40 L/min 40% oxygen flow from a home humidifier as an oxygen therapy for 4 hrs, followed by almost the same flow from a jet nebulizer, which generates positive ions, for 4 hrs. The other group received the reverse combination. MEASUREMENTS AND MAIN RESULTS During the 8-hr study, arterial blood lactate concentrations were measured every hour. There was a significant difference in the time course of blood lactate concentrations between the groups. In the group in which negative ions were first initiated for 4 hrs and positive ions thereafter, the lactate concentration decreased slightly at 3, 4, and 5 hrs and returned to the baseline concentration thereafter. In the group with the reverse combination, the lactate concentration did not change during the first 4 hrs but decreased thereafter after inhalation of negative ions. CONCLUSIONS Inspired O(2)(-) attenuates blood lactate concentrations. This may be attributed, in part, to the systemic stimulatory effect on superoxide dismutase activity, which accelerates oxidative phosphorylation in the mitochondria, thus attenuating lactate generation.