Regulation of Purine Nucleotide Metabolism in Hypoxic Liver and Intestine of Rats: Radical Scavenging Effects of Allopurinol and Oxypurinol

Gerber, Gerhard; Siems, Werner; Werner, Andreas; Stoêsser, R.; Foeldes-Papp, Zénó; Kowalewski, Jan; Schneider, Wolfram; Grune, Tilman

doi:10.1007/978-1-4684-5676-9_74

Cited by 7 publications

(7 citation statements)

References 9 publications

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“…The ATP, the ATP/ADP ratio, the ATP/AMP ratio and the GTP/GDP ratio are lowered under hypoxia (anoxia) [6]. In contrast, IMP, adenosine, inosine, guanosine and hypoxanthine accumulated simultaneously [6].…”

Section: Concentrations Of Purine Compounds In Rat Hepatocytes At Anomentioning

confidence: 98%

“…Under the hypoxia, about 51 % of the total inhaled oxygen was used for the formation of superoxide anion radicals, while under normoxic conditions, only 2.3 % entered into this pathway [6]. Figure 3 summarizes some main reaction routes of the massively formed superoxide anion radicals (O 2 •− ).…”

Section: Contribution Of Xod and Uod Mediated Hydrogen Peroxide Produmentioning

confidence: 99%

“…All these changes are reversible. During reoxygenation for 10 minutes, most of the changes are fully compensated [6].…”

Section: Concentrations Of Purine Compounds In Rat Hepatocytes At Anomentioning

confidence: 99%

“…2. The substrates hypoxanthine and xanthine are provided for the massive formation of superoxide anion radicals and hydrogen peroxide via the oxidase activity of the xanthine oxidoreductase reaction [6]. Under normoxic conditions, the oxidase activity of xanthine oxidoreductase (XOD) is inhibited in favor of its dehydrogenase activity [6].…”

Section: Formation Of Activated Oxygen Species During Hypoxiamentioning

confidence: 99%

“…Consequences of the cellular decrease in ATP are the formation of hypoxanthine and xanthine, which are the substrates for the massive formation of superoxide anion radicals and hydrogen peroxide via the oxidase activity of the xanthine oxidoreductase reaction. Under severe hypoxia, about 51 % of the total inhaled oxygen is used to form superoxide anion radicals in rat liver [Gerber et al (1989) Adv Exp Med Biol 253B, Plenum Press, New York, 497-504]. The reactivity and selectivity of the superoxide anion radical are modified by specific interactions and electron exchange.…”

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confidence: 98%

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Oxidative stress caused by acute and chronic exposition to altitude

Földes-Papp

Domej

Demel

et al. 2005

Wien Med Wochenschr

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In this article, current views on cellular and molecular biology (biochemical) mechanisms are discussed under the aspect of altitude exposition. The Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia are known [Beal et al. (2002) Proc Natl Acad Sci USA 99: 17215-17218]. The phylogenetic tree of the human species suggests that there are genetic differences in adaptation patterns to chronic hypoxic hypoxia. Five defense mechanisms are well established for lowlanders who are exposed to acute hypoxic hypoxia. Consequences of the cellular decrease in ATP are the formation of hypoxanthine and xanthine, which are the substrates for the massive formation of superoxide anion radicals and hydrogen peroxide via the oxidase activity of the xanthine oxidoreductase reaction. Under severe hypoxia, about 51 % of the total inhaled oxygen is used to form superoxide anion radicals in rat liver [Gerber et al. (1989) Adv Exp Med Biol 253B, Plenum Press, New York, 497-504]. The reactivity and selectivity of the superoxide anion radical are modified by specific interactions and electron exchange. It is commonly accepted that the superoxide anion radical in aqueous solutions has a lifetime in the millisecond range. However, electron spin resonance spectroscopy studies in a KO2/H2O/iron ion system revealed for the first time a stabilization of a part of the initially added superoxide anion radicals lasting up to hours at room temperature [Földes-Papp (1992) Gen Physiol Biophys 11: 3-38]. Superoxide anion radicals adsorbed on an oxidic iron hydrate phase in aqueous systems might function as a strong oxidant similar to that species which has been suggested to be a complex between oxygen and different valence states of iron in the initiation of lipid peroxidation by ferrous iron. There were serious doubts about the identity of alkoxy radicals. For the first time, alkoxy radicals were directly demonstrated in solution by electron spin resonance spectroscopy [Földes-Papp et al. (1991) Adv Synth Catal 333: 293-301]. The redox status in mammalian cells is mainly determined by the antioxidant glutathione, which is a key player in maintaining the intracellular redox equilibrium and in the metabolic regulation of the cellular defense against oxidative stress. As reactive oxygen species occupy an essential role in membrane damage, the idea of membrane-bound enzymatic defense mechanisms gets a new dimension [Földes-Papp et al. (1981) Acta Biol Med Ger 40: 1129-1132; Földes-Papp and Maretzki (1982) Acta Biol Med Ger 41: 1003-1008]. The steady-state between antioxidants and pro-oxidants affects the gene expression via hypoxia-induced transcription activities. The transcription factor hypoxia-inducible factor 1 (HIF-1) is a global regulator of oxygen homeostasis. As discussed in this article, hypoxia or 'oxidative stress' is accompanied by appropriate molecular adaptation mechanisms at the enzymatic or epigenetic level (enzymatic and non-enzymatic radical inhibitors, posttranslational modifications) and at the genetic level ...

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Section: Concentrations Of Purine Compounds In Rat Hepatocytes At Anomentioning

confidence: 98%

Section: Contribution Of Xod and Uod Mediated Hydrogen Peroxide Produmentioning

confidence: 99%

“…All these changes are reversible. During reoxygenation for 10 minutes, most of the changes are fully compensated [6].…”

Section: Concentrations Of Purine Compounds In Rat Hepatocytes At Anomentioning

confidence: 99%

Section: Formation Of Activated Oxygen Species During Hypoxiamentioning

confidence: 99%

mentioning

confidence: 98%

See 3 more Smart Citations

Oxidative stress caused by acute and chronic exposition to altitude

Földes-Papp

Domej

Demel

et al. 2005

Wien Med Wochenschr

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The Mechanism of Conversion of Xanthine Dehydrogenase to Oxidase and the Role of the Enzyme in Reperfusion Injury

Nishino

Tamura

1991

Advances in Experimental Medicine and Biology

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Deoxycoformycin and oxypurinol: protection against focal ischemic brain injury in the rat

Lin

Phillis

1992

Brain Research

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Regulation of Purine Nucleotide Metabolism in Hypoxic Liver and Intestine of Rats: Radical Scavenging Effects of Allopurinol and Oxypurinol

Cited by 7 publications

References 9 publications

Oxidative stress caused by acute and chronic exposition to altitude

Oxidative stress caused by acute and chronic exposition to altitude

The Mechanism of Conversion of Xanthine Dehydrogenase to Oxidase and the Role of the Enzyme in Reperfusion Injury

Deoxycoformycin and oxypurinol: protection against focal ischemic brain injury in the rat

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