Release of xanthine oxidase to the systemic circulation during resuscitation from severe hypoxemia in newborn pigs

Rootwelt, Terje; Almaas, Runar; Øyasæter, Stephanie; Møen, Atle; Saugstad, Ola Didrik

doi:10.1111/j.1651-2227.1995.tb13683.x

Cited by 9 publications

(2 citation statements)

References 24 publications

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“…In vivo there are sources of free radicals other than the neurons, such as endothelium, neutrophils, and circulating xanthine oxidase (29). Thus, the finding that the radicals produced by these neurons do not substantially contribute to neuronal death after oxygen and glucose deprivation should not be extended to a conclusion that free radicals are of minor importance in vivo as there are several sources of free radicals other than neurons.…”

Section: Discussionmentioning

confidence: 89%

Neuronal Formation of Free Radicals Plays a Minor Role in Hypoxic Cell Death in Human NT2-N Neurons

Almaas¹,

Saugstad²,

Pleasure

et al. 2002

Pediatr Res

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Free radicals are suggested to play an important role in hypoxic-ischemic neuronal death. However, the importance in human disease is not known. Furthermore, whether posthypoxic free radical formation mainly occurs in endothelium and neutrophils, or whether neuronal production is important, is not finally determined. To study this we differentiated human Ntera2 teratocarcinoma cells into postmitotic NT2-N neurons and exposed them to free radicals, hypoxia, or oxygen and glucose deprivation. These cells are devoid of nitric oxide synthase, and we hypothesized that free radicals are important mediators downstream of N-methyl-D-aspartate stimulation. Production of free radicals, evaluated with the fluorescent dyes dihydrorhodamine and 2',7'-dichlorodihydrofluorescein, was significantly higher in neurons deprived of oxygen and glucose after 40 min of reoxygenation than in normoxic cells. The antioxidant trolox, the flavonoid quercetin, thiopental, and the N-methyl-D-aspartateglutamate receptor antagonist MK-801 reduced the formation of free radicals. Treatment with the flavonoid rutin (86 Ϯ 16% of hypoxic cells without drug, p Ͻ 0.01), trolox (86 Ϯ 20%, p Ͻ 0.01), and MK-801 (57 Ϯ 12%, p Ͻ 0.01) reduced lactate dehydrogenase release after 6 h of hypoxia. Trolox, salicylate, and quercetin also significantly reduced lactate dehydrogenase release after 3 h of oxygen and glucose deprivation. The protection offered by these antioxidants was, however, limited compared with the effect of MK-801. We conclude that oxygen and glucose deprivation causes a moderate increase in the formation of free radicals in NT2-N neurons that can be Several experiments have indicated a role for free radicals in the pathogenesis of hypoxic-ischemic cell death. The xanthine oxidase inhibitor and hydroxyl radical scavenger allopurinol reduces hypoxic-ischemic brain damage in rats (1), and van Bel et al. (2) demonstrated beneficial effects of allopurinol in asphyxiated infants. Infarct size and brain edema after focal cerebral ischemia are attenuated in adult transgenic mice overexpressing CuZn SOD (3). However, brain injury after hypoxia-ischemia was exacerbated in a similar newborn mice model (4).During reperfusion after cerebral ischemia in pigs, superoxide anion is generated (5). Production of free radicals after ischemia has been reported from rat brain microvessels (6) and from fetal bovine endothelial cells (7). A substantial part of posthypoxic free radical formation in endothelium has been attributed to xanthine oxidase (7). On the other hand, ScmidElsaesser et al. (8)

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Section: Discussionmentioning

confidence: 89%

Neuronal Formation of Free Radicals Plays a Minor Role in Hypoxic Cell Death in Human NT2-N Neurons

Almaas¹,

Saugstad²,

Pleasure

et al. 2002

Pediatr Res

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“…On the other hand, it has been presumed that hepatic XOR will be released into systemic circulation upon certain noxious stimuli, such as hyperglycemic conditions, and this may aggravate vascular function impairment [ 29 ]. Rootwelt demonstrated that the release of XOR into the circulation from injured tissues after hypoxia and subsequent re-oxygenation [ 30 ]. XOR is shown to appear in the systemic circulation after ischemia reperfusion in humans [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Relationship between plasma xanthine oxidoreductase activity and left ventricular ejection fraction and hypertrophy among cardiac patients

Fujimura

Yamauchi

Murase³

et al. 2017

PLoS ONE

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Background and purposeXanthine oxidoreductase (XOR), which catalyzes purine catabolism, has two interconvertible forms, xanthine dehydrogenase and xanthine oxidase, the latter of which produces superoxide during uric acid (UA) synthesis. An association between plasma XOR activity and cardiovascular and renal outcomes has been previously suggested. We investigated the potential association between cardiac parameters and plasma XOR activity among cardiology patients.Methods and resultsPlasma XOR activity was measured by [13C2,15N2]xanthine coupled with liquid chromatography/triplequadrupole mass spectrometry. Among 270 patients who were not taking UA-lowering drugs, XOR activity was associated with body mass index (BMI), alanine aminotransferase (ALT), HbA1c and renal function. Although XOR activity was not associated with serum UA overall, patients with chronic kidney disease (CKD), those with higher XOR activity had higher serum UA among patients without CKD. Compared with patients with the lowest XOR activity quartile, those with higher three XOR activity quartiles more frequently had left ventricular hypertrophy. In addition, plasma XOR activity showed a U-shaped association with low left ventricular ejection fraction (LVEF) and increased plasma B-type natriuretic peptide (BNP) levels, and these associations were independent of age, gender, BMI, ALT, HbA1C, serum UA, and CKD stages.ConclusionsAmong cardiac patients, left ventricular hypertrophy, low LVEF, and increased BNP were significantly associated with plasma XOR activity independent of various confounding factors. Whether pharmaceutical modification of plasma XOR activity might inhibit cardiac remodeling and improve cardiovascular outcome should be investigated in future studies.

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Free Radicals in Neonatal Intensive Care

Saugstad¹

1996

Update in Intensive Care and Emergency Medicine

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Release of xanthine oxidase to the systemic circulation during resuscitation from severe hypoxemia in newborn pigs

Cited by 9 publications

References 24 publications

Neuronal Formation of Free Radicals Plays a Minor Role in Hypoxic Cell Death in Human NT2-N Neurons

Neuronal Formation of Free Radicals Plays a Minor Role in Hypoxic Cell Death in Human NT2-N Neurons

Relationship between plasma xanthine oxidoreductase activity and left ventricular ejection fraction and hypertrophy among cardiac patients

Free Radicals in Neonatal Intensive Care

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