Antioxidant and cytotoxic studies for kaempferol, quercetin and isoquercitrin

The aim of the present study was to investigate a cytotoxic oxidative cell stress related and the antioxidant profile of kaempferol, quercetin, and isoquercitrin. The flavonol compounds were able to act as scavengers of superoxide anion (but not hydrogen peroxide), hypochlorous acid, chloramine and nitric oxide. Although flavonoids are widely described as antioxidants and this activity is generally related to beneficial effects on human health, here we show important cytotoxic actions of three well known flavonoids. They were able to promote hemolysis which one was exacerbated on the presence of hypochlorous acid but not by AAPH radical. Therefore, despite they expected scavenger action over free radicals an oxidants, these compounds could be very lesive to living organisms by acting over erythrocytes and maybe other cellular types.

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Peroxynitrite: mediator of the toxic action of nitric oxide.

Acta Biochimica Polonica ◽

10.18388/abp.1996_4461 ◽

1996 ◽

Vol 43 (4) ◽

pp. 645-659 ◽

Cited By ~ 82

Author(s):

G Bartosz

Keyword(s):

Nitric Oxide ◽

Signal Transduction ◽

Superoxide Anion ◽

Toxic Action ◽

Nitric Oxide Donors ◽

Peroxynitrous Acid ◽

Protein Nitration ◽

Fast Reaction ◽

Beneficial Effects

Peroxynitrite (oxoperoxonitrate(-1)), anion of peroxynitrous acid, is thought to mediate the toxic action of nitric oxide and superoxide anion. Peroxynitrite is formed in a fast reaction between these species, reacts with all classes of biomolecules, is cytotoxic, and is thought to be involved in many pathological phenomena. Its main reactions involve one- and two-electron oxidation and nitration. Protein nitration is often used as a footprint of peroxynitrite reactions in vivo. Nitration of tyrosine and of tyrosyl residues in proteins may be an important mechanism of derangement of biochemical signal transduction by this compound. However, apparently beneficial effects of peroxynitrite have also been described, among them formation of nitric oxide and nitric oxide donors in reactions of peroxynitrite with thiols and alcohols.

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Endothelium and the effect of activated neutrophils on arterial smooth muscle

Interdisciplinary Toxicology ◽

10.1515/intox-2015-0008 ◽

2015 ◽

Vol 8 (1) ◽

pp. 44-47

Author(s):

Viktor Bauer ◽

Ruzena Sotnikova

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Sodium Nitroprusside ◽

Superoxide Anion ◽

Anion Radical ◽

Hypochlorous Acid ◽

No Synthase ◽

Relaxant Effect ◽

Activated Neutrophils ◽

Rat Thoracic Aorta

Abstract The aim of the study was to analyze the involvement of the endothelium in the effects of neutrophils (PMNL) on phenylephrine-pre-contracted isolated rings of the rat thoracic aorta and to compare their effects with those of peroxynitrite (ONOO−) and hypochlorous acid (HOCl). Activated PMNL-induced contraction of the precontracted aorta was prevented by the blockade of NO-synthase and by endothelium removal. In the endothelium-free preparations, the effect of PMNL reappeared in the presence of sodium nitroprusside. The effect of ONOO− and HOCl significantly differed from that of activated PMNL both in the presence and absence of the endothelium. It is therefore likely that neither ONOO− nor HOCl generated by transformation of superoxide anion radical (O2•−) produced by PMNL is involved in their action. Reduction of the relaxant effect of nitric oxide derived from the endothelium by O2•− seems to be the keystone mechanism in generation of PMNL-induced contraction.

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Physical Exercise and Cardiac Repair: The Potential Role of Nitric Oxide in Boosting Stem Cell Regenerative Biology

Antioxidants ◽

10.3390/antiox10071002 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1002

Author(s):

Fabiola Marino ◽

Mariangela Scalise ◽

Eleonora Cianflone ◽

Luca Salerno ◽

Donato Cappetta ◽

...

Keyword(s):

Nitric Oxide ◽

Stem Cell ◽

Physical Exercise ◽

Cell Biology ◽

Molecular Mechanisms ◽

Heart Function ◽

Stem Cell Biology ◽

Myocardial Repair ◽

Beneficial Effects

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the “nitroso-redox imbalance”. Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.

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Magnetic Field Effect in the Reaction of Recombination of Nitric Oxide and Superoxide Anion

Applied Magnetic Resonance ◽

10.1007/s00723-009-0018-2 ◽

2009 ◽

Vol 36 (2-4) ◽

pp. 195-208 ◽

Cited By ~ 11

Author(s):

Tatiana Yu. Karogodina ◽

Svetlana V. Sergeeva ◽

Dmitri V. Stass

Keyword(s):

Magnetic Field ◽

Nitric Oxide ◽

Superoxide Anion ◽

Field Effect ◽

Magnetic Field Effect

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Glutathione Participation in the Prevention of Cardiovascular Diseases

Antioxidants ◽

10.3390/antiox10081220 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1220

Author(s):

Deyamira Matuz-Mares ◽

Héctor Riveros-Rosas ◽

María Magdalena Vilchis-Landeros ◽

Héctor Vázquez-Meza

Keyword(s):

Cardiovascular Diseases ◽

Superoxide Anion ◽

Reactive Nitrogen Species ◽

Hypochlorous Acid ◽

Reduced Glutathione ◽

Heart Diseases ◽

Reactive Species ◽

Oxygen Species ◽

Cardiovascular Pathologies

Cardiovascular diseases (CVD) (such as occlusion of the coronary arteries, hypertensive heart diseases and strokes) are diseases that generate thousands of patients with a high mortality rate worldwide. Many of these cardiovascular pathologies, during their development, generate a state of oxidative stress that leads to a deterioration in the patient’s conditions associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Within these reactive species we find superoxide anion (O2•–), hydroxyl radical (•OH), nitric oxide (NO•), as well as other species of non-free radicals such as hydrogen peroxide (H2O2), hypochlorous acid (HClO) and peroxynitrite (ONOO–). A molecule that actively participates in counteracting the oxidizing effect of reactive species is reduced glutathione (GSH), a tripeptide that is present in all tissues and that its synthesis and/or regeneration is very important to be able to respond to the increase in oxidizing agents. In this review, we will address the role of glutathione, its synthesis in both the heart and the liver, and its importance in preventing or reducing deleterious ROS effects in cardiovascular diseases.

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Nitric oxide has no beneficial effects on ion transport defects in cystic fibrosis human nasal epithelium

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s004240000394 ◽

2000 ◽

Vol 441 (1) ◽

pp. 133-137 ◽

Cited By ~ 12

Author(s):

Claudia Rückes-Nilges ◽

H. Lindemann ◽

Thorsten Klimek ◽

Hiltrud Glanz ◽

Wolf-Michael Weber

Keyword(s):

Nitric Oxide ◽

Cystic Fibrosis ◽

Ion Transport ◽

Nasal Epithelium ◽

Beneficial Effects ◽

Human Nasal Epithelium

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Effect of extracellular Mg2+ on ROS and Ca2+ accumulation during reoxygenation of rat cardiomyocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.280.1.h344 ◽

2001 ◽

Vol 280 (1) ◽

pp. H344-H353 ◽

Cited By ~ 27

Author(s):

Mohammad N. Sharikabad ◽

Kirsten M. Østbye ◽

Torstein Lyberg ◽

Odd Brørs

Keyword(s):

Nitric Oxide ◽

Reactive Oxygen Species ◽

Flow Cytometry ◽

Lactate Dehydrogenase ◽

Superoxide Anion ◽

Oxygen Species ◽

No Donor ◽

Rat Cardiomyocytes ◽

Intracellular Ros ◽

Ldh Release

The effects of Mg2+ on reactive oxygen species (ROS) and cell Ca2+ during reoxygenation of hypoxic rat cardiomyocytes were studied. Oxidation of 2′,7′-dichlorodihydrofluorescein (DCDHF) to dichlorofluorescein (DCF) and of dihydroethidium (DHE) to ethidium (ETH) within cells were used as markers for intracellular ROS levels and were determined by flow cytometry. DCDHF/DCF is sensitive to H2O2 and nitric oxide (NO), and DHE/ETH is sensitive to the superoxide anion (O2 −·), respectively. Rapidly exchangeable cell Ca2+ was determined by 45Ca2+uptake. Cells were exposed to hypoxia for 1 h and reoxygenation for 2 h. ROS levels, determined as DCF fluorescence, were increased 100–130% during reoxygenation alone and further increased 60% by increasing extracellular Mg2+concentration to 5 mM at reoxygenation. ROS levels, measured as ETH fluorescence, were increased 16–24% during reoxygenation but were not affected by Mg2+. Cell Ca2+ increased three- to fourfold during reoxygenation. This increase was reduced 40% by 5 mM Mg2+, 57% by 10 μM 3,4-dichlorobenzamil (DCB) (inhibitor of Na+/Ca2+ exchange), and 75% by combining Mg2+ and DCB. H2O2 (25 and 500 μM) reduced Ca2+ accumulation by 38 and 43%, respectively, whereas the NO donor S-nitroso- N-acetyl-penicillamine (1 mM) had no effect. Mg2+ reduced hypoxia/reoxygenation-induced lactate dehydrogenase (LDH) release by 90%. In conclusion, elevation of extracellular Mg2+ to 5 mM increased the fluorescence of the H2O2/NO-sensitive probe DCF without increasing that of the O2 −·-sensitive probe ETH, reduced Ca2+ accumulation, and decreased LDH release during reoxygenation of hypoxic cardiomyocytes. The reduction in LDH release, reflecting the protective effect of Mg2+, may be linked to the effect of Mg2+ on Ca2+ accumulation and/or ROS levels.

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Hyperoxia and self- or neutrophil-generated O2 metabolites inactivate xanthine oxidase

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.5.2349 ◽

1988 ◽

Vol 65 (5) ◽

pp. 2349-2353 ◽

Cited By ~ 36

Author(s):

L. S. Terada ◽

C. J. Beehler ◽

A. Banerjee ◽

J. M. Brown ◽

M. A. Grosso ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Xanthine Oxidase ◽

Superoxide Anion ◽

Hypochlorous Acid ◽

Control Mechanism ◽

Xanthine Dehydrogenase ◽

Biological Processes ◽

Lung Endothelial Cells ◽

Cellular Control

Xanthine oxidase (XO) and xanthine dehydrogenase (XD) activities decreased in lungs isolated from rats and cultured lung endothelial cells that had been exposed to hyperoxia. Purified XO activity also decreased after addition of a variety of chemically generated O2 metabolite species (superoxide anion, hydrogen peroxide, hydroxyl radical, or hypochlorous acid), hypoxanthine, or stimulated neutrophils in vitro. XO inactivation by chemically, self-, or neutrophil-generated O2 metabolites was decreased by simultaneous addition of various O2 metabolite scavengers but not their inactive analogues. Since XO appears to contribute to a variety of biological processes and diseases, hyperoxia- or O2 metabolite-mediated decreases in XO activity may be an important cellular control mechanism.

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Cilostazol Induces eNOS and TM Expression via Activation with Sirtuin 1/Krüppel-like Factor 2 Pathway in Endothelial Cells

International Journal of Molecular Sciences ◽

10.3390/ijms221910287 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10287

Author(s):

Chih-Hsien Wu ◽

Yi-Lin Chiu ◽

Chung-Yueh Hsieh ◽

Guo-Shiang Tsung ◽

Lian-Shan Wu ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Endothelial Nitric Oxide Synthase ◽

Umbilical Vein ◽

Sirtuin 1 ◽

No Production ◽

Beneficial Effects ◽

Umbilical Vein Endothelial Cells ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Cilostazol was suggested to be beneficial to retard in-stent atherosclerosis and prevent stent thrombosis. However, the mechanisms responsible for the beneficial effects of cilostazol are not fully understood. In this study, we attempted to verify the mechanism of the antithrombotic effect of cilostazol. Human umbilical vein endothelial cells (HUVECs) were cultured with various concentrations of cilostazol to verify its impact on endothelial cells. KLF2, silent information regulator transcript-1 (SIRT1), endothelial nitric oxide synthase (eNOS), and endothelial thrombomodulin (TM) expression levels were examined. We found cilostazol significantly activated KLF2 expression and KLF2-related endothelial function, including eNOS activation, Nitric oxide (NO) production, and TM secretion. The activation was regulated by SIRT1, which was also stimulated by cilostazol. These findings suggest that cilostazol may be capable of an antithrombotic and vasculoprotective effect in endothelial cells.

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