6-formylpterin, a xanthine oxidase inhibitor, intracellularly generates reactive oxygen species involved in apoptosis and cell proliferation

2001 ◽  
Vol 30 (3) ◽  
pp. 248-259 ◽  
Author(s):  
Toshiyuki Arai ◽  
Nobuyuki Endo ◽  
Kouhei Yamashita ◽  
Masataka Sasada ◽  
Hiroko Mori ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Proliferation ◽  
Xanthine Oxidase ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Xanthine Oxidase Inhibitor

Antioxidant pyruvate inhibits cardiac formation of reactive oxygen species through changes in redox state

2000 ◽  
Vol 279 (5) ◽  
pp. H2431-H2438 ◽  
Author(s):  
Eberhard Bassenge ◽  
Olaf Sommer ◽  
Michael Schwemmer ◽  
Rolf Bünger
Keyword(s):  
Reactive Oxygen Species ◽  
Xanthine Oxidase ◽  
Nadh Oxidase ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Xanthine Oxidase Inhibitor ◽  
Ros Formation ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia-reperfusion is associated with bursts of reactive oxygen species (ROS) such as superoxide radicals (O2 −·). Membrane-associated NADH oxidase (NADHox) activity is a hypothetical source of O2 −·, implying the NADH concentration-to-NAD+ concentration ratio ([NADH]/[NAD+]) as a determinant of ROS. To test this hypothesis, cardiac NADHox and ROS formation were measured as influenced by pyruvate or l-lactate. Pre- and postischemic Langendorff guinea pig hearts were perfused at different pyruvate/l-lactate concentrations to alter cytosolic [NADH]/[NAD+]. NADHox and ROS were measured with the use of lucigenin chemiluminescence and electron spin resonance, respectively. In myocardial homogenates, pyruvate (0.05, 0.5 mM) and the NADHox blocker hydralazine markedly inhibited NADHox (16 ± 2%, 58 ± 9%). In postischemic hearts, pyruvate (0.1–5.0 mM) dose dependently inhibited ROS up to 80%. However,l-lactate (1.0–15.0 mM) stimulated both basal and postischemic ROS severalfold. Furthermore,l-lactate-induced basal ROS was dose dependently inhibited by pyruvate (0.1–5.0 mM) and not the xanthine oxidase inhibitor oxypurinol. Pyruvate did not inhibit ROS from xanthine oxidase. The data suggest a substantial influence of cytosolic NADH on cardiac O2 −· formation that can be inhibited by submillimolar pyruvate. Thus cytotoxicities due to cardiac ischemia-reperfusion ROS may be alleviated by redox reactants such as pyruvate.

Cytochemical studies of hydrogen peroxide generation in postischemic hepatocytes

1991 ◽  
Vol 260 (1) ◽  
pp. H123-H129
Author(s):  
C. F. Babbs ◽  
S. C. Salaris ◽  
J. J. Turek
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Xanthine Oxidase ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cytochemical Study ◽  
Xanthine Oxidase Inhibitor ◽  
Liver Slices ◽  
Reoxygenation Injury ◽  
Exogenous H2o2

Reoxygenation injury that occurs when blood circulation is restored to previously ischemic tissues is currently discussed as a pathophysiological entity distinct from the primary anoxic injury that develops during ischemia per se. To test the hypothesis that reoxygenation injury in hepatocytes is caused by a postischemic burst of reactive oxygen species (ROS), including superoxide radicals, O2-., and hydrogen peroxide, H2O2, we performed a cytochemical study exploiting the peroxidase activity within peroxisomes as a sensitive ultrastructural detector of intracellular H2O2 generation. The osmiophilic polymer formed when tissue peroxidase is incubated with 3,3'-diaminobenzidine (DAB) and H2O2 was used as a marker for endogenous H2O2 in rat liver slices in short-term organ culture subjected to a cycle of 60-min ischemic anoxia and 30-min reoxygenation in the presence of DAB without exogenous H2O2. Peroxisomal reaction product was quantitatively evaluated in transmission electron micrographs of systematically sampled hepatocytes. Mean densities of positive peroxisomes per 1,000 micron2 (+/- SE) in liver slices subjected to various treatments were as follows: continuous anoxia (negative control) 0 +/- 0; normoxia + exogenous H2O2 (positive control) 45 +/- 12; normoxia only 26 +/- 2; ischemia-reoxygenation 13 +/- 6; ischemia-reoxygenation + xanthine oxidase inhibitor, oxypurinol 5 +/- 3; ischemia-reoxygenation + peroxidase inhibitor, aminotriazole 7 +/- 3. Endogenous H2O2 can be detected in hepatocytes by electron microscopic cytochemistry and may in part derive from xanthine oxidase, but it is not substantially increased in the postischemic state. We conclude that hepatocytes do not exhibit a postischemic burst of reactive oxygen species that could cause reoxygenation injury.

CSIG-21. 5-ALA PDT AND TARGETING MEK/ERK SIGNALING ELICITS SYNERGISTIC ANTITUMOR EFFECTS IN DIFFUSE MIDLINE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi37-vi37
Author(s):  
Gabrielle Price ◽  
Daniel Rivera ◽  
Alexandros Bouras ◽  
Constantinos Hadjipanayis
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Proliferation ◽  
Aminolevulinic Acid ◽  
Tumor Therapy ◽  
Unmet Need ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Antitumor Effects ◽  
Genetically Engineered Mouse Model

Abstract Diffuse midline gliomas (DMGs) are highly invasive, unresectable tumors in children. To date, there is no effective treatment for DMGs. Fractionated radiotherapy (RT), currently the standard of care, has provided limited disease control. Current obstacles to treatment include the blood brain barrier (BBB) that limits systemic drug delivery, tumor therapy resistance, and brainstem infiltration. Given the unmet need for more effective DMG treatments, photodynamic therapy (PDT), with the precursor photosensitizing agent 5-aminolevulinic acid (5-ALA), is an oncologic treatment that holds promise. 5-ALA PDT of tumors occurs by targeting tumor cells that accumulate the 5-ALA metabolite, protoporphyrin IX (PPIX), with 635 nm light to create deadly reactive oxygen species (ROS). We explore the synergism of 5-ALA PDT with the MEK inhibitor, trametinib, since the RAS/MEK signaling pathway regulates tumor cell proliferation and survival and has been shown to therapeutically enhance PDT in select tumor models. We demonstrated that sub-micromolar levels of 5-ALA PDT and nanomolar levels of trametinib successfully decrease cell proliferation and induce apoptosis in multiple DMG cell lines. Cell viability assays revealed that drug response differs based on the histone mutation (H3.1 or H3.3) of the line. Mechanisms of decreased cell survival involves the generation of reactive oxygen species that induces programmed cell death. Through the use of a DMG genetically engineered mouse model, we also found 5-ALA PDT to induce apoptosis in vivo. The synergistic effects of MEK inhibition and 5-ALA PDT in vitro and apoptotic effects of 5-ALA PDT in vivo, highlights the potential therapeutic efficacy of this treatment modality.

scholarly journals Graphene and graphene oxide induce ROS production in human HaCaT skin keratinocytes: the role of xanthine oxidase and NADH dehydrogenase

Nanoscale ◽  
2018 ◽  
Vol 10 (25) ◽  
pp. 11820-11830 ◽  
Author(s):  
Marco Pelin ◽  
Laura Fusco ◽  
Cristina Martín ◽  
Silvio Sosa ◽  
Javier Frontiñán-Rubio ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Graphene Oxide ◽  
Xanthine Oxidase ◽  
Nadh Dehydrogenase ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Depolarization ◽  
Skin Keratinocytes

Graphene based nanomaterials induce a reactive oxygen species-mediated mitochondrial depolarization, caused by the activation of NADH dehydrogenase and xanthine oxidase.

Abstract 38: Reactive Oxygen Species Contribute To Aneurysmal Rupture in Mice

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Kenji Shimada ◽  
Yoshiteru Tada ◽  
Kosuke Wada ◽  
Mari Kudo ◽  
Shoko Murakami ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Xanthine Oxidase ◽  
Intracranial Aneurysms ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Gelatinase Activity ◽  
Xanthine Oxidase Inhibitor ◽  
Aneurysmal Rupture ◽  
Nadph Oxidase Inhibitor ◽  
Superoxide Scavenger

Background and Purpose: Inflammation and apoptosis are recognized as key factors for aneurysmal rupture. Reactive oxygen species (ROS) mediates both inflammation and apoptosis in vascular walls. Therefore, we hypothesized that ROS produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture. Recently we have demonstrated the feasibility of using a mouse model of intracranial aneurysms to test pharmacological therapies for the prevention of aneurysmal rupture. We tested the hypothesis by using this newly established mouse model. Methods: Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and the deoxycorticosterone acetate (DOCA) salt hypertension. Six days after aneurysm induction, we started 2-week treatment with vehicle (n=27), a superoxide scavenger (tempol; n=13), a xanthine oxidase inhibitor (oxypurinol; n=15), and a NADPH oxidase inhibitor (apocynin; n=16). Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysms with subarachnoid hemorrhage. Dihydroethidium staining and in situ zymography were performed to detect superoxide production and gelatinase activity, respectively. Results: A superoxide scavenger (tempol) significantly reduced rupture rate (vehicle vs. tempol: 74% vs. 27%, P < 0.05) (Figure1). It reduced superoxide production and gelatinase activity in aneurysmal walls (Figure2). Furthermore, the xanthine oxidase inhibitor (oxypurinol), and the NADPH oxidase inhibitor (apocynin) reduced the rupture rate (vehicle vs. oxypurinol: 74% vs. 30%, P< 0.05, vehicle vs. apocynin: 74% vs. 33%, P < 0.05). Conclusion: Our results indicate that superoxide produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture, by activating matrix metalloproteinases.

scholarly journals The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1155
Author(s):  
Olga Witkowska-Piłaszewicz ◽  
Rafał Pingwara ◽  
Anna Winnicka
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Proliferation ◽  
Immune Cell ◽  
Ex Vivo ◽  
Exercise Physiology ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Peripheral Blood Mononuclear ◽  
Before And After ◽  
Anti Inflammatory

Physical activity has an influence on a variety of processes in an athlete’s organism including the immune system. Unfortunately, there is a lack of studies regarding racehorse immune cells, especially when the horse model is compared to human exercise physiology. The aim of the study was to determine changes in immune cell proliferation, lymphocyte populations, and monocyte functionality in trained and untrained racehorses after exercise. In this study, field data were collected. The cells from 28 racehorses (14 untrained and 14 well-trained) were collected before and after exercise (800 m at a speed of about 800 m/min) and cultured for 4 days. The expression of CD4, CD8, FoxP3, CD14, MHCII, and CD5 in PBMC, and reactive oxygen species (ROS) production, as well as cell proliferation, were evaluated by flow cytometry. In addition, IL-1β, IL-4, IL-6, IL-10, IL-17, INF-γ, and TNF-α concentrations were evaluated by ELISA. The creation of an anti-inflammatory environment in well-trained horses was confirmed. In contrast, a pro-inflammatory reaction occurred in untrained horses after training. In conclusion, an anti-inflammatory state occurs in well-trained racehorses, which is an adaptational reaction to an increased workload during training.

Sign in / Sign up

Export Citation Format

Share Document