Absence of xanthine oxidase or xanthine dehydrogenase in the rabbit myocardium

Grum, Cyril M.; Ragsdale, Richard A.; Ketai, Loren H.; Shlafer, Marshal

doi:10.1016/s0006-291x(86)80157-7

Cited by 61 publications

(23 citation statements)

References 16 publications

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“…We reported blockade of hypoxanthine breakdown during anoxia by allopurinol. 4 [4][5][6][7][8]18 The conversion of xanthine to urate seems to be faster in guinea pig than in mouse and rat hearts. This should be checked with xanthine as the substrate.…”

Section: Species Differencesmentioning

confidence: 99%

Xanthine oxidoreductase activity in perfused hearts of various species, including humans.

Jong

Meer

Nieukoop

et al. 1990

Circulation Research

101

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Oxygen free radicals generated by xanthine oxidase have been implicated in cardiac damage. The activity of xanthine oxidase/reductase in adult rat heart is considerable. Its assay gives controversial results for other species, for example, rabbits and humans. Therefore, we perfused isolated hearts of various species, including explanted human hearts, to measure the conversion of exogenous hypoxanthine to xanthine and urate. We assayed these purines with high-performance liquid chromatography. The apparent xanthine oxidoreductase activities, calculated as release of xanthine plus 2x urate, were (milliunits per gram wet weight, mean +/- SEM) mice 33 +/- 3 (n = 5), rats 28.5 +/- 1.4 (n = 9), guinea pigs 14.4 +/- 1.0 (n = 5), rabbits 0.59 +/- 0.09 (n = 5), pigs less than 0.1 (n = 6), humans 0.31 +/- 0.04 (n = 7), and cows 3.7 +/- 0.8 (n = 4). In rabbit heart the conversion of hypoxanthine to xanthine was slow, and that of xanthine to urate was even slower. On the other hand, guinea pig and human heart released little xanthine, indicating that xanthine breakdown exceeds its formation. We conclude that isolated perfused mouse, rat, guinea pig, and also bovine hearts show considerable xanthine oxidoreductase activity, contrasting rabbit, porcine, and diseased human hearts.

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Section: Species Differencesmentioning

confidence: 99%

Xanthine oxidoreductase activity in perfused hearts of various species, including humans.

Jong

Meer

Nieukoop

et al. 1990

Circulation Research

101

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“…However, in dog hearts a major source of oxygen radicals is represented by the activity of endothelial xanthine oxidase (63). In contrast, hearts from rabbits (and humans) have little or no xanthine oxidase activity (64,65). Consequently, it might be speculated that the increased sarcolemmal peroxidation in the study ofRomaschin et al might be the consequence ofa large generation of oxygen radicals in the vascular lumen, whereas other mechanisms of oxygen radical generation should be considered for the increased lipid peroxidation observed in our study.…”

Section: Mda Release In the Coronary Effluentmentioning

confidence: 99%

Oxygen radicals generated at reflow induce peroxidation of membrane lipids in reperfused hearts.

Ambrosio

Flaherty²,

Duilio³

et al. 1991

J. Clin. Invest.

245

120

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To test whether generation of oxygen radicals during postischemic reperfusion might promote peroxidation of cardiac membrane lipids, four groups of Langendorff-perfused rabbit hearts were processed at the end of (a) control perfusion, (b) 30 min of total global ischemia at 370C without reperfusion, (c) 30 min of ischemia followed by reperfusion with standard perfusate, (d) 30 min of ischemia followed by reperfusion with the oxygen radical scavenger human recombinant superoxide dismutase (h-SOD). The left ventricle was homogenized and tissue content of malonyldialdehyde (MDA), an end product of lipid peroxidation, was measured on the whole homogenate as well as on various subcellular fractions. Reperfusion was accompanied by a significant increase in MDA content of the whole homogenate and of the fraction enriched in mitochondria and lysosomes. This phenomenon was not observed in hearts subjected to ischemia but not reperfused, and was similarly absent in those hearts which received h-SOD at reflow. Reperfused hearts also had significantly greater levels of conjugated dienes (another marker of lipid peroxidation) in the mitochondrial-lysosomal fraction. Again, this phenomenon did not occur in ischemic hearts or in reperfused hearts treated with h-SOD. Unlike the effect on tissue MDA and conjugated dienes, reperfusion did not significantly stimulate release of MDA in the cardiac effluent. Treatment with h-SOD was also associated with significant improvement in the recovery ofcardiac function. In conclusion, these data directly demonstrate that postischemic reperfusion results in enhanced lipid peroxidation of cardiac membranes, which can be blocked by h-SOD, and therefore is most likely secondary to oxygen radical generation at reflow. (J. Clin.

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“…Also, allopurinol, which exhibits no direct antioxidant properties at pharmacologic concentrations, displays tissue-protective actions in organ systems low in or devoid of detectable endogenous XOR activity (6). For example, both rabbit and clinical myocardial ischemia-reperfusion injury was significantly attenuated by allopurinol, despite several reports revealing that rabbit and human heart have low to undetectable amounts of XO (7)(8)(9)(10). It therefore becomes critical to understand the tissue distribution of XO and underlying mechanisms of cell injury that are mediated by a source of reactive species that is widely implicated in various pathological processes.…”

mentioning

confidence: 99%

Binding of Xanthine Oxidase to Vascular Endothelium

Houston

Estévez

Chumley³

et al. 1999

Journal of Biological Chemistry

237

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Concentrations of up to 1.5 milliunits/ml xanthine oxidase (XO) (1.1 g/ml) are found circulating in plasma during diverse inflammatory events. The saturable, high affinity binding of extracellular XO to vascular endothelium and the effects of cell binding on both XO catalytic activity and differentiated vascular cell function are reported herein. Xanthine oxidase purified from bovine cream bound specifically and with high affinity (K d ‫؍‬ 6 nM) at 4°C to bovine aortic endothelial cells, increasing cell XO specific activity up to 10-fold. Xanthine oxidase-cell binding was not inhibited by serum or albumin and was partially inhibited by the addition of heparin. Pretreatment of endothelial cells with chondroitinase, but not heparinase or heparitinase, diminished endothelial binding by ϳ50%, suggesting association with chondroitin sulfate proteoglycans. Analysis of rates of superoxide production by soluble and cell-bound XO revealed that endothelial binding did not alter the percentage of univalent reduction of oxygen to superoxide. Comparison of the extent of CuZn-SOD inhibition of native and succinoylated cytochrome c reduction by cell-bound XO indicated that XO-dependent superoxide production was occurring in a cell compartment inaccessible to CuZn-SOD. This was further supported by the observation of a shift of exogenously added XO from extracellular binding sites to intracellular compartments, as indicated by both proteasereversible cell binding and immunocytochemical localization studies. Endothelium-bound XO also inhibited nitric oxide-dependent cGMP production by smooth muscle cell co-cultures in an SOD-resistant manner. This data supports the concept that circulating XO can bind to vascular cells, impairing cell function via oxidative mechanisms, and explains how vascular XO activity diminishes vasodilatory responses to acetylcholine in hypercholesterolemic rabbits and atherosclerotic humans. The ubiquity of cell-XO binding and endocytosis as a fundamental mechanism of oxidative tissue injury is also affirmed by the significant extent of XO binding to human vascular endothelial cells, rat lung type 2 alveolar epthelial cells, and fibroblasts.

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Absence of xanthine oxidase or xanthine dehydrogenase in the rabbit myocardium

Cited by 61 publications

References 16 publications

Xanthine oxidoreductase activity in perfused hearts of various species, including humans.

Xanthine oxidoreductase activity in perfused hearts of various species, including humans.

Oxygen radicals generated at reflow induce peroxidation of membrane lipids in reperfused hearts.

Binding of Xanthine Oxidase to Vascular Endothelium

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