Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allopurinol was investigated in 3 x 6 cm congested island skin flaps in rats. Eight hours of venous occlusion produced total flap necrosis. Pretreatment with systemic allopurinol, an inhibitor of xanthine oxidase, enhanced the survival rate of hyperemic skin flaps. Xanthine oxidase activities were demonstrated in skin, and these enzyme activities were noted to increase in skin flaps during ischemia and reperfusion. Much of this increase in enzyme activity was prevented by allopurinol treatment. The xanthine oxidase system appears to be one of the sources of the superoxide radical, which may be involved in ischemic and reperfusion injury in skin.
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PMID:Effect of allopurinol on the survival of hyperemic island skin flaps. 654 51

We have investigated the possibility that xanthine oxidase-linked free radical production has a role in the genesis of arrhythmias during ischemia and reperfusion. In this study, rats were treated with allopurinol (20 mg/kg, orally, 24 hours before study, plus 20 mg/kg, iv, 15 minutes prior to study). Using an anesthetized open-chest preparation with either coronary artery occlusion for 30 minutes, or 5 minutes followed by 10 minutes reperfusion, we monitored and compared the rhythm disturbances in experimental vs. placebo-treated rats (n = 18 in each group). Allopurinol treatment reduced the incidence of ventricular tachycardia during ischemia from 88% to 50% (P less than 0.05) and the number of premature ventricular complexes from 471 +/- 120 to 116 +/- 46 (P less than 0.02), but the treatment had no effect upon the incidence or duration of ventricular fibrillation or upon mortality. In contrast, far more dramatic protection was observed during reperfusion after 5 minutes of ischemia. Allopurinol treatment reduced the incidence of ventricular fibrillation from 67% to 11% (P less than 0.01), reduced the mean duration of fibrillation from 230 +/- 70 to 14 +/- 1 seconds (P less than 0.05), and reduced mortality by half (10/18 to 4/18), although this did not reach a level of statistical significance. In addition, the mean duration of tachycardia was reduced from 83 +/- 26 to 38 +/- 8 seconds (P less than 0.05). Allopurinol pretreatment thus affords some protection against ischemia-induced arrhythmias, but a higher degree of protection against reperfusion-induced arrhythmias. Allopurinol inhibits xanthine oxidase activity, and, in turn, this inhibits superoxide radical production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ischemia and reperfusion-induced arrhythmias in the rat. Effects of xanthine oxidase inhibition with allopurinol. 654 76

High-energy phosphates in heart muscle deprived of oxygen are rapidly broken down to purine nucleosides and oxypurines. We studied the role of xanthine oxidase/dehydrogenase (EC 1.2.3.2/EC 1.2.1.37) in this process with novel high-pressure liquid chromatographic techniques. Under various conditions, including ischemia and anoxia, the isolated perfused rat heart released adenosine, inosine and hypoxanthine, and also substantial amounts of xanthine and urate. Allopurinol, an inhibitor of xanthine oxidase, greatly enhanced the release of hypoxanthine. From the purine release we calculated that the rat heart contained about 18 mU xanthine oxidase per g wet weight. Subsequently, we measured a xanthine oxidase activity of 9 mU/g wet wt. in rat-heart homogenate. When endogenous low molecular weight inhibitors were removed by gel-filtration, the activity increased to 31 mU/g wet wt. Rat myocardial xanthine oxidase seems to be present mainly in the dehydrogenase form, which upon storage at -20 degrees C is converted to the oxidase form.
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PMID:Myocardial xanthine oxidase/dehydrogenase. 657 31

Allopurinol, acting as a metabolic depressant, significantly increases flap survival in high doses, but not at doses that might be acceptable clinically. Prednisolone is highly effective in improving flap survival when the afferent blood supply is provided by small arteries such as are found in the panniculus carnosus of rabbits and in axial pattern flaps. I feel that the study should encourage plastic surgeons to experiment with drugs that sustain metabolism during ischemic periods, as a means of improving flap survival. In situations in which ischemia can be anticipated, its effects may be minimized by using such drugs before the insult.
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PMID:Improving flap survival by sustaining cell metabolism within ischemic cells: a study using rabbits. 735 May 80

The implication of different eicosanoids and oxygen free radicals in the development of pancreatic injury after an ischemia-reperfusion process has been evaluated. For this purpose we have compared the effect of allopurinol and indomethacin administration on the pancreatic levels of eicosanoids in a rat model of pancreatic ischemia-reperfusion. After 60 min of pancreatic ischemia and 2 h of reperfusion, significant increases in 6-keto-PGF1 alpha, PGE2, and LTB4 in pancreas tissue were detected. Allopurinol before the ischemic period reduced 6-keto-PGF1 alpha, PGE2, and LTB4 levels to the range of basal values, while prior indomethacin treatment significantly reduced 6-keto-PGF1 alpha and PGE2 levels, with LTB4 remaining unmodified. Increased postischemic plasma lipases were also significantly reduced by allopurinol to the range of sham-operated animals whereas indomethacin did not modify these levels. The data suggest a role for lipoxygenase metabolites in the development of pancreatic injury and the importance of the enzyme xanthine oxidase as an inductor of eicosanoid biosynthesis.
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PMID:Role of xanthine oxidase and eicosanoids in development of pancreatic ischemia-reperfusion injury. 755 51

A study was designed to investigate the possibility of reducing peritoneal adhesion formation in mice by pretreatment with allopurinol. Allopurinol, at a dose of 35 mg/kg of body weight/d significantly reduced the severity of peritoneal adhesions (P < .001), and also the neutrophil response to ischemia (P < .05). Tissue myeloperoxidase activity at the site of ischemic injury was significantly lower in the allopurinol-treated mice at the end of 2 weeks (P < .001). However, xanthine oxidase was undetectable in both control and allopurinol-treated mice. These observations suggest that allopurinol reduces the severity of peritoneal adhesion formation in mice, possibly by reducing the neutrophil response to ischemia.
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PMID:Allopurinol reduces the severity of peritoneal adhesions in mice. 759 27

With microdialysis, we monitored cardiac interstitial fluid (ISF) levels of allopurinol, its metabolites, and the adenine nucleotide breakdown products (ANBP), inosine, hypoxanthine (HYP), xanthine (Xa), uric acid (UA) in dogs that received 1 and 10 mg/kg allopurinol intravenously (i.v.). Half-life (t1/2) of drug penetration into the heart was dose independent (1.8 min), whereas for the 10-mg/kg dose terminal elimination t1/2 (96 min) was much prolonged and ISF clearance (9.6 l/min kg) was reduced as compared with that induced by 1 mg/kg (28 min and 30.4 l/min kg) probably due to capacity limitation of allopurinol conversion to oxypurinol by Xa dehydrogenase/oxydase (Xa D/O). Inhibition of Xa D/O activity by allopurinol resulted in a dose-dependent increase in ISF HYP and Xa levels and a decrease in UA level. For a 10-mg/kg dose, maximal effect was attained approximately 40 min after drug injection. Allopurinol (1 mg/kg) given 30 min after the start of 40-min coronary artery occlusion during ischemia entered the ischemic zone ISF very slowly as compared with that of the control zone; the no-reflow phenomenon was evident because the levels became similar in both zones only 15 min after initiation of reperfusion. To examine cardioprotective efficiency, we administered allopurinol (10 mg/kg) 40 min before 40-min occlusion; it had little effect on total ANBP release during ischemia but facilitated washout of ANBP from the ischemic zone during reperfusion, thus manifesting protective efficacy against reperfusion injury and no-reflow. As shown by the lack of ischemia-induced increase in ISF Xa, myocardial Xa D/O activity was completely blocked by allopurinol.
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PMID:Allopurinol: kinetics, inhibition of xanthine oxidase activity, and protective effect in ischemic-reperfused canine heart as studied by cardiac microdialysis. 759 24

Investigations were carried out to determine the antiulcer effects of silymarin, the hepatoprotective principle of Silybum marianum L. Gaertn., in gastric injury induced by ischemia-reperfusion and its effects on mucosal myeloperoxidase activity, an index of polymorphonuclear leukocyte infiltration, after injury in rats. These results were compared with those from rats that received allopurinol, an inhibitor of xanthine oxidase and with those from rats made neutropenic by prior administration of dexamethasone and methotrexate. Pretreatment with silymarin prevented post-ischemic mucosal injury. The mean ulcer indexes (U.I.) of rats treated with 25, 50 mg, and 100 mg silymarin/kg body weight (4.79 +/- 0.75, 4.50 +/- 0.81, and 3.63 +/- 0.74, respectively) were significantly lower (p < 0.05, 0.05, and p < 0.005) than that of control rats. Allopurinol was considerably more potent in reducing the U.I. than silymarin, with a calculated U.I. of 2.33 +/- 0.45, p < 0.001. These protective effects were specifically related to a reduction in the number of neutrophils in the gastric mucosa. Reduction in the numbers of circulating neutrophils by treating rats with methotrexate (MPO level of 7.2 x 10(-2) +/- 0.56 x 10(-2)U/mg wt) and dexamethasone (MPO level of 6.97 x 10(-2) +/- 0.68 x 10(-2)U/mg wt) also resulted in a significant reduction in the susceptibility to gastric damage induced by ischemia-reperfusion. These results suggest that neutrophils play an important role in the gastric mucosal dysfunction associated with ischemia-reperfusion. These findings also indicate that the inhibitory effects of silymarin on neutrophil function may contribute significantly to its gastroprotective actions.
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PMID:Gastroprotection induced by silymarin, the hepatoprotective principle of Silybum marianum in ischemia-reperfusion mucosal injury: role of neutrophils. 775 16

Copper Fenton systems (Cu(II)/H2O2 and Cu(II)/Asc) inactivated the lipoamide reductase and enhanced the diaphorase activity of pig-heart lipoamide dehydrogenase (LADH). Cupric ions alone were less effective. As a result of Cu(II)/H2O2 treatment, the number of titrated thiols in LADH decreased from 6 to 1 per subunit. NADH and ADP (not NAD+ or ATP) enhanced LADH inactivation by Cu(II). NADH also enhanced the effect of Cu(II)/H2O2. Dihydrolipoamide, dihydrolipoic acid, Captopril, acetylcysteine, EDTA, DETAPAC, histidine, bathocuproine, GSSG and trypanothione prevented LADH inactivation. 100 microM GSH, DL-dithiothreitol, N-(2-mercaptopropionylglicine) and penicillamine protected LADH against Cu(II)/Asc and Cu(II), whereas 1.0 mm GSH and DL-dithiothreitol also protected LADH against Cu(II)/H2O2. Allopurinol provided partial protection against Cu(II)/H2O2. Ethanol, mannitol, Na benzoate and superoxide dismutase failed to prevent LADH inactivation by Cu(II)/H2O2 or Cu(II). Catalase (native or denaturated) and bovine serum albumin protected LADH but that protection should be due to Cu binding. LADH inhibited deoxyribose oxidation and benzoate hydroxylation by Cu(II)/H2O2. It is concluded that site-specifically generated HO, radicals were responsible for LADH inactivation by Cu(II) Fenton systems. The latter effect is discussed in the context of ischemia-reoxygenation myocardial injury.
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PMID:Inactivation of heart dihydrolipoamide dehydrogenase by copper Fenton systems. Effect of thiol compounds and metal chelators. 775

1. The preventive effect of allopurinol on reduced glutathione and lipid peroxide levels of the liver and the accompanying ultrastructural changes during liver ischemia was investigated in guinea pigs. 2. Liver glutathione levels decreased significantly while lipid peroxide levels increased slightly in the ischemic group. 3. Allopurinol administered before ischemia resulted in a reverse significant increase in liver glutathione levels and a significant decrease in lipid peroxide levels indicating a protective effect upon cell membrane during ischemia. 4. On the other hand, electron microscopic changes in the liver associated with ischemia could not be altered by allopurinol.
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PMID:The effect of allopurinol on the liver ultrastructure, reduced glutathione and lipid peroxide levels during liver ischemia in guinea pigs. 795 42


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