Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.6 (catalase)
55,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diabetogenic effect of the quinonoid compound alloxan is not understood in detail although it supposedly involves reactions mediated by alloxan and oxygen radicals. These reactive species may form extra- or intracellularly and cause cell damage through a variety of complex interactions with several macromolecules. The purpose of this study was to elucidate early (less than or equal to 60 min) effects of alloxan and reducing agents (cysteine and ascorbic acid) on cultured macrophages, as assayed by the trypan blue dye exclusion test and the sensitive fluorescein diacetate and propidium iodide (FDA/PI) double staining technique. During the reactions between alloxan and reducing agents, oxygen was consumed as a sign of superoxide anion radical formation. When alloxan alone was added to two different culture media without serum, oxygen was still consumed, indicating formation of oxygen radicals due to the occurrence of reducing substances in cell culture media. This finding demonstrated the necessity of performing further studies in solutions without reducing capacity, e.g. in phosphate-buffered saline. The experiments showed that exposure of normal and malignant macrophages to alloxan and reducing substances resulted in rapidly occurring plasma membrane damage and ensuing cell death. Separate addition of catalase, desferrioxamine or superoxide dismutase resulted in evident, slight and no protection, respectively. The combinations of (i) catalase and desferrioxamine, and (ii) catalase, desferrioxamine and superoxide dismutase, however, inhibited cell damage in a pronounced and complete way, respectively. The results are interpreted as indicating cell damage due to the extracellular formation of hydrogen peroxide and hydroxyl radicals. The latter in close proximity to the cells and acting on the plasma membrane, while the former, after diffusing into the cell, may have several intracellular targets. The FDA/PI technique proved its value as a quantifiable method for the evaluation not only of cell death but also of cell damage with computer-based fluorometry.
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PMID:Effects of alloxan and reducing agents on macrophages in culture. 195 48

The mechanism of the reaction between alloxan and GSH has been studied in the presence and absence of superoxide dismutase. Excess GSH reduced alloxan to dialuric acid, which underwent subsequent autoxidation, thus establishing a redox cycle in which O2 and GSH in excess of the alloxan concentration were consumed. The major reaction products were H2O2 and GSSG. At each cycle, a small fraction of the alloxan reacted with GSH to form a 305 nm-absorbing adduct that gradually accumulated. In the presence of SOD, alloxan was reduced by GSH, but increasing concentrations of GSH progressively inhibited redox cycling as shown by decreased rates of O2 uptake and GSH oxidation. With GSH: alloxan or dialuric acid molar ratios of greater than 8-10:1, redox cycling was almost completely suppressed. A mechanism based on known reactions of GSH and dialuric acid is proposed. Alloxan and GSH, with an iron chelate present as catalyst, caused the hydroxylation of salicylate, an indicator of hydroxyl radical production. Hydroxylation was inhibited by catalase but not by superoxide dismutase, and it is attributed to the Fenton reaction in which the ferric catalyst is reduced by dialuric acid.
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PMID:Glutathione-mediated redox cycling of alloxan. Mechanisms of superoxide dismutase inhibition and of metal-catalyzed OH. formation. 253 42

The diabetogenic action of alloxan is believed to involve oxygen free radicals and iron. Incubation of glutathione (GSH) and alloxan with rat liver ferritin resulted in release of ferrous iron as assayed by spectrophotometric detection of ferrous-bathophenanthroline complex formation. Neither GSH nor alloxan alone mediated iron release from ferritin. Superoxide dismutase (SOD) and catalase did not affect initial rates of iron release whereas ceruloplasmin was an effective inhibitor of iron release. The reaction of GSH with alloxan resulted in the formation of the alloxan radical which was detected by ESR spectroscopy and by following the increase in absorbance at 310nm. In both instances, the addition of ferritin resulted in diminished alloxan radical detection. Incubation of GSH, alloxan, and ferritin with phospholipid liposomes also resulted in lipid peroxidation. Lipid peroxidation did not occur in the absence of ferritin. The rates of lipid peroxidation were not affected by the addition of SOD or catalase, but were inhibited by ceruloplasmin. These results suggest that the alloxan radical releases iron from ferritin and indicates that ferritin iron may be involved in alloxan-promoted lipid peroxidation.
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PMID:Alloxan- and glutathione-dependent ferritin iron release and lipid peroxidation. 253 98

1. The cytotoxicity of the polyphenolic potential male antifertility agent gossypol was investigated on isolated mouse islets cells. 2. Gossypol shared many properties with the diabetogenic agent alloxan. 3. Gossypol (0.1-1.0 mmol/l) induced a concentration-dependent increase of Trypan Blue uptake by the cells, indicating an increase of membrane permeability to the dye. 4. Trypan Blue uptake induced by 0.5 mmol/l gossypol was inhibited by concomitant incubation of the cells with enzymatic (200 mg/l superoxide dismutase, 200 mg/l catalase, 3 mmol/l cytochrome-c), or low-molecular weight (50 mmol/l D-mannitol) scavengers of oxygen radicals, and the metal chelator diethylenetriaminepentacetic acid (DTPA) (50 mumol/l). 5. The results support the hypothesis that gossypol is B-cytotoxic by generation of noxious free radicals and that when proposing gossypol as a male antifertility agent, studies to exclude gossypol as a diabetogenic agent should first be performed in vivo.
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PMID:Gossypol-induced free radical toxicity to isolated islet cells. 268 1

The autoxidation of dialuric acid, a process which is believed to be of crucial importance in the diabetogenic action of alloxan, was found to be strongly catalysed by copper, iron and manganese. Superoxide radical and hydrogen peroxide were generated in both the uncatalysed and the metal-catalysed reactions. In contrast, hydroxyl radical was formed during dialuric acid autoxidation only in the presence of added iron salts. Production of the latter radical was strongly inhibited by catalase but only weakly by superoxide dismutase, implying that the metal-catalysed Haber-Weiss reaction is of comparatively little importance in hydroxyl radical generation from dialuric acid.
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PMID:Dialuric acid autoxidation. Effects of transition metals on the reaction rate and on the generation of "active oxygen" species. 333 41

Previous experiments on alloxan diabetogenicity suggest that alloxan increases the permeability of B-cell plasma membranes by generation of noxious free radicals. Whether the radicals are generated intra- or extracellularly has however been disputed. To test if extracellularly generated free radicals could decrease trypan blue exclusion of dispersed islet cells, a radical-generating solution of xanthine oxidase/hypoxanthine was employed. The solution increased dye uptake by cells in the cell suspension. Superoxide dismutase and catalase but not scavengers of hydroxyl radicals protected against the increase in dye uptake. Both L- and D-glucose protected the cells from injury. It is concluded that extracellularly generated free radicals induce damage to the plasma membrane of islet cells. The result strengthens the hypothesis of plasma membrane damage by extracellularly generated free radicals as the primary event in alloxan diabetogenicity and may provide a link for explanation of damage caused by islet inflammation in juvenile diabetes.
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PMID:Effect of extracellularly generated free radicals on the plasma membrane permeability of isolated pancreatic B-cells. 351 30

A study has been made of the damage incurred by normal and Plasmodium falciparum-infected human erythrocytes following exposure to a variety of oxidant-generating systems. Hydrogen peroxide, produced by the glucose-glucose oxidase system, increased methaemoglobin formation within normal erythrocytes while normal levels of oxyhaemoglobin were maintained. Exposure to products of the xanthine-xanthine oxidase interaction did not have the same effect. Malondialdehyde measurements indicated that the host cell membranes of parasitized cells had undergone lipid peroxidation even before exposure to the oxidant-generating systems. Lipid peroxidation of normal and parasitized cell membranes was increased upon exposure to reagent-grade hydrogen peroxide and alloxan: this increase was not observed following exposure to the two enzyme-substrate systems that generated reactive oxygen intermediates. In addition, the effects of parasitism on intracellular levels of catalase and superoxide dismutase were assessed. Normal and parasitized erythrocytes were found to possess similar levels of these enzymes, which protect against oxidant-induced damage. It was therefore concluded that the increased susceptibility of infected cells to oxidant damage was probably not related to any decrease in the function of these enzymes.
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PMID:Damage to malaria-infected erythrocytes following exposure to oxidant-generating systems. 352 61

The contents of Cu, Zn-superoxide dismutase and catalase isolated and purified from the rat liver at the terminal stages of alloxan diabetes were decreased by 40% and 15%, respectively, as compared to the control. It can be concluded that the decrease in superoxide dismutase and catalase activity in experimental alloxan diabetes is mainly connected with the decline in the content of these proteins at the terminal stages of the disease, this, probably, being the result of DNA degradation and RNA transport disturbances under the effect of oxygen active forms.
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PMID:[Quantitative changes in Cu, Zn-superoxide dismutase and catalase isolated from the liver of alloxan diabetic rats]. 382 10

Chemiluminescence induced in isolated islets from rat pancreas by the diabetogenic drugs, alloxan and streptozotocin, has been measured. The assay system consisted of 3 microM of luminol, 10 islets, and 100 microM of alloxan or 500 microM of streptozotocin in 5 ml Krebs-Ringer bicarbonate buffer containing 16 mM of Hepes (pH 7.4). Alloxan-induced chemiluminescence appeared very rapidly and lasted more than 5 min. On the other hand, streptozotocin failed to produce chemiluminescence over a period of 60 min after addition. The presence of superoxide dismutase (1000 U/ml) and/or catalase (100 U/ml) markedly suppressed alloxan-induced chemiluminescence. These results suggest that alloxan acts as an exogenous free radical generator in pancreatic islets, but that streptozotocin does not. The involvement of superoxide anion and hydrogen peroxide in production of chemiluminescence by alloxan suggests that the hydroxyl radical may mediate this chemiluminescence.
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PMID:Chemiluminescence as an index of drug-induced free radical production in pancreatic islets. 622 39

We have shown previously that alloxan and streptozotocin, two major diabetogenic agents, cause DNA strand breaks in rat pancreatic islets and stimulate nuclear poly(ADP-ribose) synthetase, thereby depleting intracellular NAD level and inhibiting proinsulin synthesis (Okamoto, H. (1981) Mol. Cell. Biochem. 37, 43-61; Yamamoto, H., Uchigata, Y., and Okamoto, H. (1981) Nature 294, 284-286). In the present study, superoxide dismutase and catalase, scavengers of radical oxygens, were found to protect against islet DNA strand breaks and inhibition of proinsulin synthesis induced by alloxan. The radical scavengers did not affect islet DNA strand breaks or inhibition of proinsulin synthesis induced by streptozotocin. On the other hand, compounds that inhibit islet nuclear poly(ADP-ribose) synthetase were found to protect against alloxan- as well as streptozotocin-induced inhibition of proinsulin synthesis. The poly(ADP-ribose) synthetase inhibitors were ineffective in protection against DNA strand breaks induced by the agents. These results may provide an important clue for elucidating the prevention of insulin-dependent diabetes as well as for understanding the cause of diabetes.
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PMID:Protection by superoxide dismutase, catalase, and poly(ADP-ribose) synthetase inhibitors against alloxan- and streptozotocin-induced islet DNA strand breaks and against the inhibition of proinsulin synthesis. 628 Dec 56


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