Determination of the mechanism of free radical generation in human aortic endothelial cells exposed to anoxia and reoxygenation.

Zweíer, Jay L.; Broderick, Raymond; Kuppusamy, Periannan; Thompson-Gorman, S. L.; Lutty, Gerard A.

doi:10.1016/s0021-9258(19)51062-6

Cited by 219 publications

(26 citation statements)

References 24 publications

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“…These observations confirm previous data reported for other anoxia models, suggesting that the cell alterations started during anoxia and increased during re-oxygenation. 1,2,4,15,21 The simultaneous demonstration of an altered respiratory function and free radical production confirmed our hypothesis that the mitochondrial respiratory chain was damaged and responsible, at least partially, for the production of free radicals that could be primarily superoxide anions. However, we can not exclude a cytosol production of superoxide anion by hypoxia-activated xanthine-oxidase, as previously suggested.…”

Section: Discussionsupporting

confidence: 77%

“…However, we can not exclude a cytosol production of superoxide anion by hypoxia-activated xanthine-oxidase, as previously suggested. 15,16 In the presence of the two superoxide anion scavengers, SOD and Tiron, the intensity of EPR signals was partially reduced. Tiron was more potent than SOD; this could be explained by a higher capacity of Tiron to cross the cell membrane and reach the site (membranes, cytosol or mitochondria) where superoxide anions are produced.…”

Section: Discussionmentioning

confidence: 99%

“…(A/R), and to demonstrate the production of oxygen free radicals and reactive species, with subsequent lipid peroxidation, in organs [9][10][11][12][13] and cultured cells, [14][15][16] such as human umbilical vein endothelial cells. These endothelial cells have been demonstrated to be resistant to long periods of anoxia, maintaining 100% viability after 24 h at 0-1% oxygen, but showing cellular dysfunctions at re-oxygenation.…”

Section: Introductionmentioning

confidence: 99%

“…8 Aortic endothelial cells were more sensitive to anoxia with 5 h of anoxia resulting in a 50% loss of viability, cell dysfunctions and defects of lipid metabolism favouring peroxidation of membrane phospholipids. 18 Zweier et al 15,16 demonstrated by the EPR spin trapping technique that, at re-oxygenation after 1 h of anoxia, human aortic endothelial cells produced superoxide free radicals that further reacted with iron to produce hydroxyl radicals. In this study, xanthine oxidase was implicated as the primary source of this radical generation.…”

Section: Introductionmentioning

confidence: 99%

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Oxygen consumption and electron spin resonance studies of free radical production by alveolar cells exposed to anoxia: inhibiting effects of the antibiotic ceftazidime

Mouithys‐Mickalad¹,

Mathy-Hartert²,

Du³

et al. 2002

Redox Report

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By EPR spectroscopy, we investigated free radical production by cultured human alveolar cells subjected to anoxia/re-oxygenation (A/R), and tested the effects of ceftazidime, an antibiotic previously demonstrated to possess antioxidant properties. Two A/R models were performed on type II pneumocytes (A549 cell line), either on cells attached to culture dishes (monolayer A/R model; 3.5 h of anoxia, 30 min of re-oxygenation) or after cell detachment (suspension A/R model; 1 h of anoxia, 10 min of re-oxygenation). Ceftazidime and selective inhibitors (SOD, Tiron, L-NMMA) were added before anoxia. Free radical production was assessed by the EPR spin trapping technique. Oxygen consumption was monitored, in parallel with EPR studies, in the suspension A/R model. The production of free radical species was demonstrated by the generation of PBN-radical adducts: (a(N) = 15.2 G) in the monolayer A/R model and a six-line EPR spectrum (a(N) = 15.7 G and a(H) = 2.7 G) in the suspension A/R model. A kinetic study performed by oximetry, in parallel with EPR spectroscopy, demonstrated marked alterations of the cell respiratory function and that the free radical production started during anoxia and increased during re-oxygenation. In the suspension A/R model, the amplitude of EPR spectra were decreased upon the addition of 200 U/ml SOD (37% inhibition), 0.1 mM Tiron (67% inhibition) and 1 mM L-NMMA (43% inhibition). Addition of 1 mM ceftazidime decreased the amplitude of EPR spectra (37% inhibition) in both A/R models. Complementary in vitro EPR studies demonstrated that CAZ scavenged the hydroxyl radical (produced by the Fenton reaction). The protective effect of ceftazidime in the cell model could thus be linked to its ability to scavenge superoxide anions, nitrogen-derived species and hydroxyl radicals.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Oxygen consumption and electron spin resonance studies of free radical production by alveolar cells exposed to anoxia: inhibiting effects of the antibiotic ceftazidime

Mouithys‐Mickalad¹,

Mathy-Hartert²,

Du³

et al. 2002

Redox Report

View full text Add to dashboard Cite

show abstract

“…Esta atividade está na base de outra ligação do molibdénio à saúde humana: envolvimento em doenças mediadas por ROS, as quais se postulam ocorrer quando a produção de ROS fica desregulada e/ou é excessiva e ultrapassa os mecanismos de defesa antioxidante. Têm sido sugeridos vários mecanismos de doença mediados por ROS e molibdoenzimas, em particular na lesão de isquemia e noutras doenças cardiovasculares [71][72][73][74][75][76][77][78][79][80][81][82][83][84][85], as quais constituem uma das principais preocupações da nossa Sociedade ocidental. A capacidade da XO e AO para gerarem NO em condições de hipóxia (como descrito acima; eq.…”

Section: A Vida Com Molibdéniounclassified