All-trans Arachidonic acid generates reactive oxygen species via xanthine dehydrogenase/xanthine oxidase interconversion in the rat liver cytosol in vitro

The effects of ofloxacin, ciprofloxacin and balofloxacin on the reactive oxygen species (ROS) levels generated by human neutrophils was examined in vitro; ROS generated in a cell-free, xanthine–xanthine oxidase system was also assessed. The species investigated were superoxide radical anion (O2−), hydrogen peroxide (H2O2) and hydroxyl radical (OH·). Both ofloxacin and ciprofloxacin markedly decreased the levels of O2−, H2O2 and OH· generated by human neutrophils. On the other hand, these drugs did not affect any of the ROS examined in the xanthine-xanthine oxidase system. Balofloxacin showed no significant effect on ROS generated by either system. The present study indicates that ofloxacin and ciprofloxacin may exert an anti-inflammatory action by reducing the potent ROS species excessively generated by neutrophils at the sites of inflammation.

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Arachidonic acid-induced apoptosis in rat hepatoma AS-30D cells is mediated by reactive oxygen species.

Acta Biochimica Polonica ◽

10.18388/abp.2009_2506 ◽

2009 ◽

Vol 56 (4) ◽

Cited By ~ 12

Author(s):

Dorota Dymkowska ◽

Lech Wojtczak

Keyword(s):

Reactive Oxygen Species ◽

Arachidonic Acid ◽

Apoptotic Cell ◽

Reactive Oxygen ◽

Water Soluble ◽

Oxygen Species ◽

Irreversible Inhibitor ◽

Induced Apoptosis ◽

Rat Hepatoma

Arachidonic acid at micromolar concentrations produced a drastic increase of the generation of reactive oxygen species (ROS) in rat hepatoma AS-30D cells cultivated in vitro along with an increase in the incidence of apoptotic cell death. Both processes were prevented by trolox, a water-soluble tocopherol derivative, and tempol, a known antioxidative agent. A synthetic hybrid of lipoic acid and trolox or preincubation with N-acetylcysteine were less effective. Preincubation of the cells with etomoxir, a known highly specific irreversible inhibitor of carnitine-palmitoyltransferase I, partly decreased the ROS formation induced by arachidonic acid but it did not affect the increase in apoptosis. Cumulatively, these results indicate that apoptosis induced in hepatoma cells by arachidonic acid is mediated by ROS. They also suggest that this effect is due to arachidonic acid as such and not to its mitochondrial oxidative metabolites.

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Kinetic analysis of reactive oxygen species generated by the in vitro reconstituted NADPH oxidase and xanthine oxidase systems

The Journal of Biochemistry ◽

10.1093/jb/mvr051 ◽

2011 ◽

Vol 150 (2) ◽

pp. 173-181 ◽

Cited By ~ 17

Author(s):

Emiko Sato ◽

Takayuki Mokudai ◽

Yoshimi Niwano ◽

Masahiro Kohno

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Kinetic Analysis ◽

Xanthine Oxidase ◽

Reactive Oxygen ◽

Oxygen Species

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Reactive Oxygen Species Formed in Vitro and in Cells: Role of Thiols(GSH). Model Studies with Xanthine Oxidase and Horseradish Peroxidase

Biological Reactive Intermediates III - Advances in Experimental Medicine and Biology ◽

10.1007/978-1-4684-5134-4_48 ◽

1986 ◽

pp. 505-512 ◽

Cited By ~ 2

Author(s):

Heribert Wefers ◽

Helmut Sies

Keyword(s):

Reactive Oxygen Species ◽

Horseradish Peroxidase ◽

Xanthine Oxidase ◽

Reactive Oxygen ◽

Oxygen Species ◽

Model Studies ◽

In Cells

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AB0841 ALTERED XANTHINE OXIDASE AND XANTHINE DEHYDROGENASE ACTIVITIES IN RED BLOOD CELLS AS A CONTRIBUTION TO AUTOIMMUNE ANEMIA APPEARANCE IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3639 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1444.1-1444

Author(s):

E. Mozgovaya ◽

A. Trofimenko ◽

S. Bedina ◽

S. Spitsina ◽

M. Mamus ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Reactive Oxygen Species ◽

Red Blood Cells ◽

Xanthine Oxidase ◽

Blood Cells ◽

Reactive Oxygen ◽

Xanthine Dehydrogenase ◽

Enzymatic Activities ◽

Oxygen Species ◽

Metabolism Enzymes

Background:Rheumatoid arthritis (RA) is severe autoimmune joint disease, accompanied by a wide variety of extra-articular manifestations. Anemia is one of the most common organ involvements in RA, being diagnosed in 36-65% patients. Iron metabolism alterations, shortened RBC lifespan, and impaired erythropoiesis in bone marrow are believed to play a leading role in RA-related anemia development. These processes in RA can be mediated by increased effect of proinflammatory cytokines, including IFNγ and TNFα, and similar mechanisms could contribute to high xanthine oxidoreductase (XOR) expression. This enzyme makes multiple pathophysiological effects, some of which can be related to the development of anemia in RA. Reactive oxygen species generated by XOR are capable, in particular, of damaging cell membranes, exerting influence on iron mobilization from ferritin in liver, and inducing changes in intestinal iron absorption.Objectives:Evaluation of changes in XOR interconvertible forms (xanthine oxidase and xanthine dehydrogenase) activities in RBC of RA patients.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. 75 RA patients with verified RA were enrolled in the study. The diagnosis was verified using the ACR/EULAR criteria (2010). The reference group consisted of 35 healthy individuals. Хanthine oxidase (XO, ЕС 1.17.3.2) and xanthine dehydrogenase (XDG, ЕС 1.17.1.4) activities were measured in lysed red blood cells by spectrophotometric method as previously described [1]. The enzymatic activities were expressed as nmol/min/ml and normalized to 1×109 cells/ml. Statistical comparison tests were selected in according to common guidelines. Central tendencies were expressed as means±SEM. Differences were considered significant when p<0.05.Results:Mean age of RA patients was 43.9±0.97 years, and mean RA duration was 8.5±0.3 years. Extra-articular manifestations were diagnosed in 32 (42.7%) RA patients and 17 (53.1%) of them had anemia. We revealed substantial changes in XO and XDG activities in lysed RBC of RA patients with anemia. Increased XO activity and decreased XDG activity were observed in comparison with healthy controls (р<0.001 for both enzymes). In parallel with the increase in DAS28 index, significant growth of XOD/XDG coefficient was observed, which was caused by both XOD activity elevation and XDG activity reduction in lysed RBC (p<0.001 for both enzymes). Enzymatic activities depended also on the extra-articular RA manifestations. Mean XO activity was higher and mean XDG activity were lower in patients with extra-articular manifestations (p<0.05 for both enzymes), but the extent of changes was substantially less comparing to anemia.Conclusion:Autoimmune inflammation in RA is accompanied by changes in enzymatic activities of XOR interconvertible forms and their ratio. Transformation of XDG into КО ultimately leads to significant increase in the generation of reactive oxygen species that have a damaging effect on lipids, proteins and other cellular components, and specifically in RBC. This fact may be one of the reasons for their premature damage and development of anemia in RA.References:[1]Zborovskaya I.A., et al. Influence of analgetics on plasma and lymphocytic activity of the purine metabolism enzymes in rheumatoid arthritis patients. Russian Journal of Pain 2018;3:47Disclosure of Interests:None declared

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The origin of reactive oxygen species in mouse embryos cultured in vitro

Development ◽

10.1242/dev.113.2.551 ◽

1991 ◽

Vol 113 (2) ◽

pp. 551-560 ◽

Cited By ~ 2

Author(s):

M.M. Nasr-Esfahani ◽

M.H. Johnson

Keyword(s):

Reactive Oxygen Species ◽

Cell Cycle ◽

Xanthine Oxidase ◽

Reactive Oxygen ◽

Oxygen Species ◽

Embryonic Genome ◽

M Phase ◽

Enzyme Superoxide Dismutase ◽

Development In Vitro

The increase in production of reactive oxygen species such as H2O2 at the G2/M phase of the second cell cycle may be related to the in vitro block to development of mouse 2-cell embryos. The occurrence of the H2O2 rise is independent of the activation of the embryonic genome and of passage through the S, G2 and M phases of the first cell cycle and G1 and M phases of the second cell cycle, but does require the activation of the unfertilized oocyte. The H2O2 is produced via dismutation of superoxide by the enzyme superoxide dismutase. Production of superoxide via mitochondrial, NADPH-oxidase and xanthine/xanthine oxidase systems has been investigated. The evidence suggests that superoxide, and thereby H2O2, is produced by the xanthine/xanthine oxidase system, but an involvement of the other superoxide generating systems has not been excluded. The relation between H2O2 and development in vitro is discussed.

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The Effect of Roxithromycin on the Generation of Reactive Oxygen Species In Vitro

Journal of International Medical Research ◽

10.1177/030006059602400104 ◽

1996 ◽

Vol 24 (1) ◽

pp. 27-32 ◽

Cited By ~ 9

Author(s):

H Akamatsu ◽

S Nishijima ◽

M Akamatsu ◽

I Kurokawa ◽

H Sasaki ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Xanthine Oxidase ◽

Reactive Oxygen ◽

Human Neutrophils ◽

Oxygen Species ◽

Oxidase System ◽

Superoxide Radical Anion ◽

A Cell ◽

Radical Generation

The effect of roxithromycin (ROM), a new oral semisynthetic macrolide, on the generation of reactive oxygen species (ROS), using human neutrophils and a cell-free, xanthine-xanthine oxidase system was examined. The species investigated were the superoxide radical anion (O2−), hydrogen peroxide (H2O2), and the hydroxyl radical (OH·). ROM effectively inhibited the generation of O2−, H2O2 and OH· by human neutrophils. On the other hand, the drug did not markedly affect the ROS levels generated in the xanthine-xanthine oxidase system. The present study indicates that ROM may exert an anti-inflammatory action by inhibiting neutrophil oxygen radical generation at the sites of inflammation.

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Effect of reactive oxygen species on K+ contractures in the rat diaphragm

Journal of Applied Physiology ◽

10.1152/jappl.1998.84.3.948 ◽

1998 ◽

Vol 84 (3) ◽

pp. 948-953 ◽

Cited By ~ 8

Author(s):

John M. Lawler ◽

Z. Hu ◽

W. S. Barnes

Keyword(s):

Reactive Oxygen Species ◽

Xanthine Oxidase ◽

Reactive Oxygen ◽

Fiber Bundles ◽

Oxygen Species ◽

Rat Diaphragm ◽

Membrane Excitability ◽

Excitation Contraction Coupling ◽

Contraction Coupling

Reactive oxygen species (ROS) are postulated to alter low-frequency contractility of the unfatigued and fatigued diaphragm. It has been proposed that ROS affect contractility through changes in membrane excitability and excitation-contraction coupling. If this hypothesis is true, then ROS should alter depolarization-dependent K+contractures. Xanthine oxidase (0.01 U/ml) + hypoxanthine (1 mM) were used as a source of superoxide anion eliciting oxidative stress on diaphragm fiber bundles in vitro. Diaphragm fiber bundles from 4-mo-old Fischer 344 rats were extracted and immediately placed in Krebs solution bubbled with 95% O2-5% CO2. After 10 min of equilibration, a K+ contracture (Pre; 135 mM KCl) was induced. Fiber bundles were assigned to the following treatment groups: normal Krebs-Ringer (KR; Con) and the xanthine oxidase system (XO) in KR solution. After 15 min of treatment exposure, a second (Post) K+contracture was elicited. Mean time-to-peak tension for contractures was significantly decreased in Post vs. Pre (16.0 ± 0.7 vs. 19.8 ± 1.0 s) with XO; no change was noted with Con. Furthermore, peak contracture tension was significantly higher (31.5%) in the XO group Post compared with Pre; again, no significant change was found with KR. The relaxation phase was also altered with XO but not with KR. Additional experiments were conducted with application of 1 mM hypoxanthine, with results similar to the Con group. We conclude that the application of ROS altered the dynamics of K+ contractures in the rat diaphragm, indicating changes in voltage-dependent excitation-contraction coupling.

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