Influence of oxypurinol on colitis induced in rat colon by trinitrobenzene sulfonic acid treatment.
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Adenine Nucleotides↗
Biomedical subjects
W Siems
Publications and source records attributed to W Siems.
ATP-producing and consuming processes of Ehrlich mouse ascites tumor cells in proliferating and resting phases.
The extents of ATP-yielding and consuming processes in Ehrlich mouse ascites tumor cells during the proliferating and resting growth phase were compared. In the resting phase the total ATP production was decreased by one-third. The ATP supply by oxidative phosphorylation was drastically reduced, whereas the rate of glycolysis stayed nearly constant. All ATP-consuming processes investigated, i.e., protein turnover, Na+/K(+)-ATPase, Ca2(+)-ATPase, and RNA synthesis, were decreased proportionally with the total ATP consumption.
Adenosine Triphosphate↗
Inhibition of Langerhans cell ATPase and contact sensitization by lanthanides--role of T-suppressor cells.
Lanthanides are rare earths, elements 55-71 in the periodic table, that are of interest in biologic systems as isomorphic competitors for calcium binding sites. Lanthanides were tested for their inhibitory influence on the Ca++/Mg(++)-dependent ATPase of epidermal langerhans cells in vitro, and on the immunologic function of Langerhans cells in vivo. The trivalent ions of lanthanides, lanthanum, and cerium completely inhibited the ATPase staining of Langerhans cells in vitro. When mice were sensitized with dinitrofluorobenzene on skin sites pretreated with topical lanthanum chloride, and challenged on untreated ear skin, a markedly reduced contact hypersensitivity response was observed. This hyporesponsiveness was found to be antigen specific, and could be passively transferred to naive syngeneic animals recipients by CD4-CD8+ spleen cells. These results suggest that inhibition of the epidermal Langerhans cell surface ATPase by application of topical lanthanum and the induction of antigen-specific immunologic tolerance may be related events.
Adenosine Triphosphatases↗
Superoxide dismutase promotes ATP and GTP restoration of rat small intestine during postischaemic reperfusion.
The small intestine of rats was prepared according to a procedure which is taken for preservation and transplantation in clinical practice. The blood supply of the rat intestine was completely interrupted for 30 min in situ. During this period the lumen of the intestine was rinsed with Ringer-lactate solution. This ischaemic period was followed by 10 min of reperfusion. As a result a decrease in ATP, and GTP concentrations, and of the total adenine nucleotide content during the preservation period occurred. In animals pretreated with superoxide dismutase (i.v. application; superoxide dismutase preparation from human erythrocytes) an accelerated restoration of nucleotide concentrations during the reperfusion period was observed. From the beneficial effect of superoxide dismutase it can be concluded, that there is a considerable formation of active species of oxygen which disturb the energy generation by the mitochondrial respiratory chain during ischaemia/re-oxygenation.
Adenine Nucleotides↗
Identification of metabolic pathways of the lipid peroxidation product 4-hydroxynonenal by enterocytes of rat small intestine.
The cytotoxic lipid peroxidation product 4-hydroxynonenal (HNE1) is rapidly metabolized in enterocytes. The degradation of HNE and other aldehydic products of lipid peroxidation processes seems to be an antioxidative defense system. The metabolism of HNE was studied in suspensions of rat enterocytes at 37 degrees C, pH 7.4 and at initial HNE concentration of 100 microM. About 70% of the HNE were degraded within three minutes of incubation. Main products of HNE which were identified in enterocytes were the glutathione-HNE-1:1-conjugate, the hydroxynonenoic acid and the 1,4-dihydroxynonene. Furthermore, the formation of metabolites of the tricarboxylic acid cycle is suggested. The quantitative share of HNE binding to proteins was low with about 1% of total HNE consumption after three minutes of incubation.
Aldehydes↗
Discrepancy between biochemical normalization and morphological recovery of jejunal mucosa during postischemic reperfusion in presence of the xanthine oxidase inhibitor oxypurinol.
An increased formation of oxygen free radicals in the reperfused rat small intestine is concluded from accumulations of oxidized glutathione, of thiobarbituric acid-reactive substances and of 4-hydroxynonenal. Xanthine oxidase inhibition prevented these biochemical changes. The histological and electronmicroscopic studies of intestinal sucosa showed significant structural deteriorations already at the end of the ischemic period obviously due to disturbances of cellular energy metabolism. The extent of dosage was increased during the reperfusion without qualitative changes of the pattern of structural dosage. The beneficial effects of oxypurinol on biochemical criteria which occurred already in the early phase of reperfusion were not reflected in significant morphological differences within the first hour of reperfusion. Differences of morphological findings between oxypurinol-treated and untreated animals could be observed after longer periods of reperfusion--during the regeneration of the tissue.
Animals↗
Aldehyde and nucleotide separations by high-performance liquid chromatography. Application to phenylhydrazine-induced damage of erythrocytes and reticulocytes.
High-performance liquid chromatographic (HPLC) techniques were used for the determination of aldehydes as lipid peroxidation products and of nucleotide concentrations in rabbit red blood cells exposed to phenylhydrazine hydrochloride. Aldehydes were determined by derivatization to dinitrophenylhydrazones, followed by thin-layer chromatographic and HPLC separation with methanol-water on an ODS column. Nucleotides and their derivatives were measured by ion-pair reversed-phase HPLC gradient elution with 10 mM ammonium phosphate buffer containing 2 mM tetrabutylammonium phosphate on ODS columns. The sensitivity of mature erythrocytes was compared with that of reticulocytes against the toxicological effects of phenylhydrazine. For both cell types an increase in aldehyde concentrations, especially of 4-hydroxynonenal, and a decline in both energy-rich nucleoside triphosphate and NAD+ were demonstrated.
Aldehydes↗
Interrelation between nucleotide degradation and aldehyde formation in red blood cells. Influence of xanthine oxidase on metabolism: an application of nucleotide and aldehyde analyses by high-performance liquid chromatography.
The mechanism by which hypoxia leads to irreversible cellular damage is poorly understood. A decrease in purine nucleotides is common to all ischaemic tissues, yielding hypoxanthine as the substrate of the xanthine oxidase reaction. Excessive production of radicals via xanthine oxidase induces peroxidation of unsaturated fatty acids, accompanied with the formation of aldehydes. The nucleotides and aldehydes were determined by high-performance liquid chromatography (HPLC) of red blood cell extracts. Nucleotides and their derivatives were determined by HPLC on an ODS column and elution with 10 mM phosphate buffer containing 2 mM tert.-butylammonium phosphate. The aldehyde production in glucose deprived red blood cells was stimulated by addition of xanthine oxidase and by inhibition of different haemotype enzymes with sodium azide. Aldehydes were analysed by derivatization to dinitrophenylhydrazones, followed by thin-layer chromatographic and HPLC separation with aqueous methanol on an ODS column. The HPLC methods presented are appropriate for the determination of nucleotides, nucleosides and nucleobases, in addition to alkenals and hydroxyalkenals in extracts of oxidatively stressed red blood cells.
Aldehydes↗
Balancing of energy-consuming processes of rat hepatocytes.
A method for the quantification of energy consuming processes described by Siems et al. for reticulocytes and by Müller et al. for ascites tumour cells was applied to balance the ATP-consumption of isolated rat hepatocytes. On the basis of decreased coupled respiration rates following the specific inhibition of energy-requiring reactions, the energy demands of protein turnover, nucleic acid synthesis, Na+/K(+)-ATPase and Ca2(+)-transport of hepatocytes in different incubation media were assessed. These processes together with urea synthesis account for about 60 per cent of the total energy consumption in a glucose and amino acid-enriched Eagle/Borsook medium. The metabolic flux rates of total ATP-consumption and ATP-consumption of single energy-requiring processes in hepatocytes are compared with those in reticulocytes and different tumour cell types.
Adenosine Triphosphate↗
Long term effects of monthly low dose whole body irradiation on the glutathione status and thiobarbituric acid-reactive substances in different organs of male Wistar rats.
Male Wistar-H-rats were exposed monthly to a 60cobalt-source low dose whole body irradiation (0.25 Gy, total dose: 4.5 Gy). The glutathione disulphide:total glutathione ratio, the concentration of thiobarbituric acid-reactive substances and the activities of glutathione peroxidase and glutathione transferase in eight different organs and blood were analysed. The low dose irradiation is accompanied by distinct peroxidative changes in organs. These oxidative loadings occur in the small intestine, the spleen and the kidneys. The measurements of glutathione status and of thiobarbituric acid-reactive substances are proposed as sensitive parameters for low dose radiation induced changes.
Animals↗
Nucleotide status in erythrocytes of rats infected with Pl. berghei.
Nucleotide concentrations in erythrocytes of rats infected with Plasmodium berghei were measured by ion-pair reversed-phase HPLC. UTP and GTP levels were higher in highly infected red blood cells obtained after density separation. The infected red blood cells possess higher hypoxanthine, adenine, and adenosine levels.
Animals↗
Nucleotide and glutathione status in erythrocytes of children undergoing chronic hemodialysis under erythropoietin treatment.
Recombinant human erythropoietin (rhEPO) used for the treatment of children with renal anemia is an effective stimulus of erythroid proliferation and differentiation. The increases of reticulocytes and of the hematocrit values give the possibility to renounce further blood transfusions in dialysis patients. There are no beneficial in vivo effects of rhEPO on the glutathione status and on the nucleotide contents of red blood cells. Therefore, indices for stabilizing effects of rhEPO on the circulating red blood cells cannot be due to glutathione and nucleotide metabolism.
Adolescent↗
Metabolism of purine and pyrimidine compounds in erythrocytes of tumor-bearing mice.
The pattern of purine and pyrimidine derivatives was studied in the erythrocytes of C3HA and ICR mice during Hepatoma 22 and Ehrlich ascites tumor cell growth. Concentrations of purine nucleotides, nucleosides and nucleobases of host erythrocytes were changed after the implantation of the tumors. The host erythrocytes markedly concentrated adenine and guanine nucleotides both during logarithmic and plateau phase of tumor growth (5th and 11-12th days after inoculation of the tumor). The contents of nucleosides and nucleobases in the red blood cells were decreased during the logarithmic growth phase but restored within the plateau phase.
Animals↗
Effects of phenylhydrazine hydrochloride on energy metabolism in rabbit erythrocytes and reticulocytes.
The effects of 1, 5 and 20 mmol/l phenylhydrazine hydrochloride on energy metabolism of rabbit erythrocyte and reticulocyte were studied. Significant depression of glycolysis, accompanied by loss of adenine nucleotides, mainly due to an extensive decline of ATP, was found in erythrocytes. Energy metabolism of reticulocytes appears to be more sensitive to deleterious effects of this drug. The declines of ATP and sum of all adenine nucleotides, as well as the accumulation of hypoxanthine were twofold in reticulocyte-rich red cell suspensions compared with suspensions of mature erythrocytes. It can be concluded that these changes are the consequence of lower energy production due to phenylhydrazine hydrochloride-induced inhibition of oxidative phosphorylation.
Adenine Nucleotides↗
Interrelationships between purine nucleotide degradation and radical formation during intestinal ischaemia and reperfusion: an application of ion-pair high-performance liquid chromatography of nucleotides, nucleosides and nucleobases.
There are peroxidative changes during the reperfusion of the rat small intestine following a 1h period of total ischaemia. That is demonstrated by the increases of the concentrations of glutathione disulphide and of thiobarbituric acid-reactive substances. An important source of the active oxygen species leading to peroxidations is the degradation of purine nucleotides. The nucleotides and their derivatives were measured by an ion-pair reversed-phase high-performance liquid chromatographic separation in a single analysis within 40 min. Modification of the elution gradient resulted in a high resolution of nucleosides and nucleobases, including allopurinol and oxypurinol. The decrease of the nucleoside triphosphate concentration and the increase of nucleoside monophosphate concentration, followed by accumulations of nucleosides and nucleobases in the course of the ischaemia were measured. During reperfusion the nucleotide pools are filled up. Restoration of adenosine triphosphate and guanosine triphosphate can be accelerated by application of the xanthine oxidoreductase inhibitor allopurinol. Pretreatment of the animals with allopurinol also diminished the formation of glutathione disulphide and thiobarbituric acid-reactive substances.
Animals↗
Regulation of purine nucleotide metabolism in hypoxic liver and intestine of rats: radical scavenging effects of allopurinol and oxypurinol.
The relationship between nucleotide catabolism and generation of activated oxygen species was investigated in liver, hepatocytes and small intestine of rats. In severe hypoxia nucleotide degradation via xanthine oxidase and urate oxidase requires about half of the oxygen consumed. Data on the changes of nucleobase compounds in rat hepatocytes and small intestine during ischemia and reoxygenation and the effects of allopurinol and oxypurinol thereon are presented. From EPR measurements it is concluded that OH. radicals induce reactions of allopurinol yielding long-living products which are able to react with DMPO-OH with loss of its radical properties.
Allopurinol↗
Adenine uptake by human erythrocytes.
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Adenine↗
Radical formation in the rat small intestine during and following ischemia.
Oxidative loading during the reperfusion of the proximal jejunum of rats following a one hour-period of complete ischemia was demonstrated in in vivo-experiments by the increases of the GSSG: total glutathione ratio and the concentration of TBA-RS. The pretreatment of the animals with the xanthine oxidoreductase inhibitor allopurinol diminished the accumulation of GSSG and of TBA-RS. It was concluded that the purine nucleotide degradation is an important source of oxygen reduction products in reoxygenated small intestine. The tissue concentrations of nucleotides, nucleosides and nucleobases were measured by an ion-pair reversed-phase HPLC separation. There occurred fast declines of ATP and GTP concentrations during ischaemia leading to temporary increases of nucleoside mono- and diphosphate pools. The hypoxanthine concentration is increased about twentyfold during oxygen deficiency. The ATP and GTP restoration during the reperfusion was accelerated in presence of allopurinol. The shares of the beneficial allopurinol effects are not yet clarified.
Animals↗