Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of captopril and enalaprilat, 2 angiotensin-converting enzyme (ACE) inhibitors, to scavenge superoxide anion radical was examined. With use of a number of superoxide-generating systems, such as xanthine-xanthine oxidase, phorbol myristate acetate-activated neutrophils, auto-oxidizing dihydroxyfumarate, and auto-oxidation of epinephrine to adrenochrome, captopril was seen not to scavenge superoxide directly, because it did not inhibit superoxide-dependent cytochrome c or nitro-blue tetrazolium reduction. Superoxide-dependent cytochrome c reduction was inhibited only when captopril was preincubated with a lower concentration of cytochrome c (22 microM). This effect was due to a decrease in the concentration of cytochrome c, because captopril reduced cytochrome c directly. When this effect was compensated for, no cytochrome c reduction induced by superoxide was observed. Captopril inhibited the auto-oxidation of epinephrine to adrenochrome at pH 10.2 where this auto-oxidation is superoxide-dependent, and at pH 7.8 where it is superoxide-independent and superoxide dismutase insensitive. It appears that captopril, in this respect, acted as a nonspecific antioxidant, probably by reducing an intermediate in the complex oxidation of epinephrine to adrenochrome. Therefore, caution may be used in interpreting the role of captopril in the attenuation of reperfusion-induced myocardial dysfunction and in attributing this effect to the inhibition of free radical mechanism.
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PMID:Captopril and enalaprilat do not scavenge the superoxide anion. 215 92

We postulated that Captopril may be capable of acting as a scavenger of free radicals, and performed in vitro studies using harvested human neutrophils. We studied the effect of Captopril on the reduction of Fe3+ cytochrome c by stimulated PMN's. Captopril acts as a reducing agent in this system, and is capable of reducing Fe3+ cytochrome c by itself. NADPH oxidase was harvested from PMA-stimulated human PMN's. Captopril inhibited the activity of this enzyme as assessed by the disappearance of NADPH determined spectrophotometrically. Since similar inhibition could be demonstrated with the superoxide scavenger superoxide dismutase, further studies were conducted using a DTNB assay of the terminal sulfhydryl group of Captopril, in the presence of a biochemical generator of superoxide (hypoxanthine/xanthine oxidase). We were unable to demonstrate disappearance of the thiol group in this system, suggesting that reaction of the SH group with 02- is unlikely under our conditions. We conclude that Captopril may interfere with human PMN NADPH oxidase in vitro.
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PMID:Captopril--a potential free radical scavenger: inhibition of PMN NADPH oxidase. 284 20

Thiol compounds have been reported to abolish hypoxanthine/xanthine oxidase induced luminol chemiluminescence and this effect has been attributed to scavenging of superoxide (O2-)/(H2O2) produced from hypoxanthine/xanthine oxidase. Yet other workers have reported that thiol compounds have shown little, if any, reactivity towards O2-/H2O2. The aim of this study was to examine the discrepancy between these two sets of findings further. Captopril (a thiol angiotensin-converting enzyme (ACE) inhibitor) and MPG (a simple thiol) were observed to abolish hypoxanthine/xanthine oxidase induced chemiluminescence. The reactivity of captopril and MPG towards O2-/H2O2 was then determined by measurement of thiol oxidation in captopril and MPG after their incubation with hypoxanthine/xanthine oxidase. Incubation (at 10 min, 37 degrees C) with 4 mM hypoxanthine/0.03 u ml-1 xanthine oxidase resulted in 7% and 20% thiol oxidation in captopril and MPG (at 1 mM) respectively. Captopril and MPG, therefore, appeared to be ineffective scavengers of oxidants produced by hypoxanthine/xanthine oxidase. Captopril and MPG also did not affect urate production or oxygen consumption by xanthine oxidase which indicated that captopril and MPG quench luminol chemiluminescence by a mechanism that excludes the inhibition of xanthine oxidase. Hypoxanthine/xanthine oxidase induced luminol chemiluminescence may, therefore, be an unsuitable method for measuring free radical scavenging activity by drugs.
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PMID:Does luminol chemiluminescence detect free radical scavengers? 765 90

The effects of a range of free-radical scavenging drugs on luminol-enhanced chemiluminescence (CL) generated by porcine leukocytes, following activation by two nonreceptor-mediated stimulants, phorbol myristate acetate (PMA; a protein kinase activator) and ionomycin (a cation ionophore), and by xanthine plus xanthine oxidase (X-XO), have been examined. Superoxide dismutase (0.1 units/mL) and catalase (50 units/mL) inhibited X-XO, but they were ineffective in leukocyte suspensions except at concentrations 500 times and 20 times higher. Sodium azide (10(-5) to 10(-3) M) caused a marked inhibition in CL production in activated leukocytes, but not of X-XO CL. The antioxidants, glutathione (10(-3) M) and L-ascorbic acid (10(-3) M) were ineffective in activated leukocytes, but caused total inhibition of X-XO-induced CL. Mannitol (100 mM) had no effect on chemiluminescence in either system. Captopril (10(-3) M) produced an inhibition of CL in both systems and this inhibition was significantly modified by pH. Thus, the present study has established a standard screening procedure for the assessment of free-radical scavenging activity using activated porcine leukocytes and xanthine-xanthine oxidase.
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PMID:Characterization of a method for the detection of drugs with free radical scavenging activity using porcine leukocytes. 783 5

We investigated whether captopril, an angiotensin-converting enzyme (ACE) inhibitor with a sulfhydryl group, enalaprilat, an ACE inhibitor without a sulfhydryl group, and cysteine, an amino acid with a sulfhydryl group but no ACE-inhibiting properties, could scavenge hydrogen peroxide and prevent oxidant-induced cell injury. When 0.1-2.5 mM concentrations of captopril, cysteine, or enalaprilat were incubated with xanthine oxidase and hypoxanthine for 0-120 min, the recovery of hydrogen peroxide was significantly (P < 0.001) reduced in the presence of captopril or cysteine, whereas enalaprilat had no effect on the recovery of hydrogen peroxide. Captopril and cysteine could not scavenge hydrogen peroxide when the sulfhydryl group was blocked with N-ethylmaleimide. When human renal tubular epithelial cells and human umbilical vein endothelial cells were exposed to hydrogen peroxide, oxidant-induced depletion of ATP and efflux of [3H]adenine metabolites was mildly reduced in the presence of captopril or cysteine but was not altered by enalaprilat. Cysteine was more effective in preventing oxidant-induced cell injury than captopril. We conclude that because of its sulfhydryl group, captopril at millimolar concentrations can scavenge hydrogen peroxide and can slightly reduce, but does not eliminate, oxidant-induced cell injury.
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PMID:Captopril scavenges hydrogen peroxide and reduces, but does not eliminate, oxidant-induced cell injury. 838

Puromycin aminonucleoside (PAN) nephropathy in rats has been induced by the intraperitoneal injections of PAN. One group of animals which received PAN has been treated simultaneously with captopril (angiotensine converting enzyme-ACE-inhibitor) with the aim to test whether continuing treatment with captopril along with PAN injections would be able to modulate the toxic effects of PAN. The third group of rats was given only captopril. Morphological changes in the kidney were evaluated by scanning electron microscopy that showed the loss of podocyte foot processes in the kidney of PAN treated animals but also in the kidney of captopril treated ones as well as in the animals treated with both drugs simultaneously. Reduced glutathione content, catalase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), xanthine oxidase activities as well as lipid peroxides were investigated in rat blood and kidney. Captopril given alone produced a significant decrease of plasma lipid peroxides, but it did not show any significant effect on investigated antioxidative factor levels neither in blood nor in the kidney. PAN given alone produced a significant depletion of plasma lipid peroxides, kidney catalase and erythrocyte GSH-Px activity as well as a significant increase of plasma catalase and erythrocyte SOD activity. Treatment of animals with both drugs simultaneously resulted in a significant increase of erythrocyte SOD activity and a significant decrease of plasma lipid peroxides, erythrocyte GSH-Px and kidney SOD activities. Kidney xanthine oxidase activity showed a significant increase in both PAN and PAN plus captopril treated animals in comparison with the values of captopril treated rats. These data suggest that PAN changes the antioxidative factor pattern in rat blood and kidney. Contrary to our expectations that captopril may protect the toxic effects of PAN it only to a certain extent modifies these effects showing protective effect only on tissue catalase activity.
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PMID:Does captopril change oxidative stress in puromycin aminonucleoside nephropathy? 1104 Dec 86