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:1.15.1.1 (superoxide dismutase)
58,858 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydrogen peroxide produces marked antigonadotropic and lytic actions in luteal cells, but the effects of superoxide, the archetypal oxygen radical, are unknown. Xanthine oxidase generates superoxide, and the activity of this enzyme, and purine substrate, are increased under ischemia, such as that seen at luteal regression. We therefore examined the actions of xanthine oxidase on luteal cells to assess the effects of this enzyme and the superoxide anion on luteal function. Xanthine oxidase, in the presence of hypoxanthine (50 microM), produced marked inhibition of LH-sensitive cAMP and progesterone production with complete inhibition at 25 mU/ml and half-maximal inhibition at about 5 mU/ml. These antigonadotropic actions of xanthine oxidase were rapid with maximal effects within 5 min, followed several minutes later by substantial depletion of ATP. Heat, superoxide dismutase, and catalase or catalase alone abolished the actions of xanthine oxidase. While depletion of ATP by xanthine oxidase was prevented by 3-amino-benzamide, an inhibitor of DNA repair, inhibition of cAMP and progesterone production was still evident. Xanthine oxidase also inhibited progesterone synthesis stimulated by 8-bromo-cAMP. Isobutylmethylxanthine, a cAMP phosphodiesterase inhibitor, did not reverse the inhibition of cAMP accumulation by xanthine oxidase, and the enzyme had no effect on LH receptor binding activity. Since catalase reversed the effects of xanthine oxidase, we conclude that superoxide was rapidly dismuted to hydrogen peroxide and mediated the antigonadotropic and antisteroidogenic actions of xanthine oxidase in luteal cells. The sensitivity of luteal cells to xanthine oxidase raises the possibility that this enzyme may serve as a significant source of hydrogen peroxide in the corpus luteum.
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PMID:Inhibition of gonadotropin action and progesterone synthesis by xanthine oxidase in rat luteal cells. 170 32

Experiments were carried out to provide evidence of the effect of L-arginine (L-Arg), its analogue NG-monomethyl-L-arginine (MeArg) and of some nitrovasodilators (sodium nitroprusside, NaNP; 3-morpholino-sydnonimine, SIN-1) which spontaneously release nitric oxide (NO) on ischemia-reperfusion injury, histamine release and mast cell degranulation, occurring after multiple ligature and release of the left anterior descending (LAD) coronary artery in isolated perfused guinea-pig hearts. The reopening of the LAD coronary artery leads to a release of histamine related to a decrease in microdensitometry of cardiac mast cells and to calcium overload. The perfusion of the heart with NO-donors significantly reduces either the release of histamine, the loss of mast cell metachromasia and the overload of calcium. These effects were potentiated by SOD. The results suggest that the endogenous formation of NO and molecules able to generate NO have a role in the prevention of post-ischemic tissue injury.
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PMID:The effect of nitric oxide generators on ischemia reperfusion injury and histamine release in isolated perfused guinea-pig heart. 171 36

We tested the efficacy of preischemic and postischemic systemic treatment with 30,000 units polyethylene glycol-conjugated superoxide dismutase in a reperfusion model of focal cerebral ischemia. Forty-one anesthetized cats underwent 2 hours' occlusion of the left middle cerebral artery and both common carotid arteries followed by 4 hours of reperfusion. Cats were blindly assigned to one of three groups: treatment with vehicle (10% polyethylene glycol in saline, n = 17), pretreatment with drug 3 hours before ischemia (n = 12), and posttreatment with drug at the time of reperfusion (n = 12). Size of the ischemic injury was calculated from 2,3,5-triphenyltetrazolium chloride staining. Injury in the caudate nucleus was significantly reduced with pretreatment (28 +/- 6% of ipsilateral caudate volume, mean +/- SEM) compared with the vehicle (56 +/- 8%). Posttreatment did not significantly ameliorate caudate injury (46 +/- 10%). Between the first and second hours of ischemia ipsilateral caudate blood flow determined using microspheres increased significantly from 11 +/- 4 to 16 +/- 5 ml/min/100 g with pretreatment, but blood flow remained constant throughout ischemia with vehicle (8 +/- 2 ml/min/100 g) and posttreatment (10 +/- 3 ml/min/100 g). The size of cortical injury (vehicle, 17 +/- 5%; pretreatment, 11 +/- 3%; posttreatment, 17 +/- 5% of hemispheric volume) did not differ significantly among groups. Somatosensory evoked potential recovery did not differ among groups. We conclude that pretreatment with conjugated superoxide dismutase can ameliorate the extent of injury in an end-artery region, such as the caudate nucleus, in a reperfusion model of focal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conjugated superoxide dismutase reduces extent of caudate injury after transient focal ischemia in cats. 171 62

In an ischemia-reperfusion model obtained in isolated perfused guinea pig heart by means of a double ligature of the left anterior descending coronary artery, the reperfusion of the ischemic myocardium leads to a release of lactate dehydrogenase and histamine, related to a decrease in the microdensitometry of cardiac mast cells and to a tissue calcium overload. The perfusion of the heart with L-arginine and with nitric oxide donors significantly reduces the release of histamine, the loss of mast cell metachromasia and calcium overload. These effects were potentiated by superoxide dismutase.
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PMID:Effect of nitric oxide generators on ischemia-reperfusion injury and histamine release in isolated perfused guinea pig heart. 171 88

Acetaldehyde (AA), the first product of ethanol metabolism, has been suggested as an important mediator in alcoholic pancreatitis, but experimental evidence has not been convincing. Prior work using the isolated perfused canine pancreas preparation has suggested that toxic oxygen metabolites generated by xanthine oxidase (XO) may mediate the early injury in pancreatitis. Xanthine oxidase is capable of oxidizing AA, and during this oxidation free radicals are released. The hypothesis that acute alcoholic pancreatitis may be initiated by AA in the presence of active XO (converted from xanthine dehydrogenase [XD]) was tested in the authors' experimental preparation by converting XD to XO by a period of ischemia, and infusing AA. Control preparations remained normal throughout the 4-hour perfusion (weight gain, 7 +/- 4 g; amylase activity, 1162 +/- 202 U/dL). One hour of ischemia or infusion of AA at 25 mg/hr or at 50 mg/hr without ischemia did not induce changes in the preparation. Acetaldehyde at 250 mg/hr induced minimal edema and weight gain (16 +/- 4 g; p less than 0.05), but not significant hyperamylasemia. Changes also were not observed when 1-hour ischemia was followed by a bolus of ethanol (1.5 g) or sodium acetate (3.0 g), or by infusion of 25 mg/hr of AA. One hour of ischemia followed by infusion of AA at 50 mg/hr or at 250 mg/hr induced edema, hemorrhage, weight gain (22 +/- 7 g [p less than 0.05] and 26 +/- 17 g [p less than 0.05]) and hyperamylasemia (2249 +/- 1034 U/dL [p less than 0.05] and 2602 +/- 1412 U/dL [p less than 0.05]). Moreover infusion of AA at 250 mg/hr after 2 hours of ischemia potentiated the weight gain (62 +/- 20 g versus 30 +/- 14 g [p less than 0.05]), but not the hyperamylasemia (3404 +/- 589 U/dL versus 2862 +/- 1525 U/dL) as compared with 2 hours of ischemia alone. Pancreatitis induced by 1 hour of ischemia followed by AA at 50 mg/hr could be inhibited by pretreatment with the free radical scavengers superoxide dismutase and catalase and ameliorated with the XO inhibitor allopurinol. The authors conclude that AA, in the presence of active XO, can initiate acute pancreatitis in the isolated canine pancreas preparation and may be important in the initiation of acute alcoholic pancreatitis in man. Toxic oxygen metabolites appear to play an important intermediary role.
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PMID:The role of acetaldehyde in the pathogenesis of acute alcoholic pancreatitis. 172 Jun 11

The production of oxygen free radicals can be stimulated by excess iron, cadmium, nickel, and the like. Inversely, copper, zinc, and selenium inhibit production, either via their own action or via antiradical metalloenzymes. The study involved determining the effect of zinc deficiency combined with chronic ethanol administration on the status of blood and tissue free radicals, as well as on cardiac function in isolated, perfused rats' hearts. Animals were fed a basic diet containing residual zinc at 0.2-0.3 ppm. Following a zinc deficiency lasting 5 wk, which during the last 4 wk was accompanied by chronic ethanol administration, hearts were submitted to ischemia for 30 min in vitro, followed by reperfusion. Biochemical analyses (zinc, superoxide dismutase, malondialdehyde, conjugated dienes, and so on) were performed in the blood and in the homogenates of different organs. The experimental zinc deficiency caused a slight decrease of superoxide dismutase activity, accompanied by increased production of peroxidated lipids. Ethanol administration appeared to increase the levels of peroxidated lipids in the heart. Finally, the combination of zinc deficiency and ethanol administration had very harmful effects, especially on lipid peroxidation and contractile function of the isolated, perfused heart in preischemic conditions.
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PMID:Zinc deficiency, ethanol, and myocardial ischemia affect lipoperoxidation in rats. 172 83

To clarify the relationship between calcium metabolism and free radical damage during the reperfusion period following ischemia, we investigated the effect of superoxide dismutase (SOD) on changes in cytosolic free calcium, cortical blood flow, and histologic changes following focal cerebral ischemia and reperfusion in 12 cats. Using indo-1, a fluorescent intracellular Ca2+ indicator, we simultaneously measured changes in the Ca2+ signal ratio (400:500 nm), NADH signal (464 nm), and reflectance (340 nm) during ultraviolet excitation (340 nm) directly from the cortex in vivo. The middle cerebral artery (MCA) was occluded for 1 h; only cats in which the EEG amplitude was depressed to less than 10% of control during the occlusion were entered into the study. Starting 2 min prior to release of the occlusion and continuing for 4 min, SOD (10,000 U/kg) was slowly infused in six cats, while in six cats, the vehicle only was infused. During MCA occlusion, the Ca2+ signal ratio increased significantly in both groups with no significant difference between the groups. During reperfusion, the Ca2+ signal ratio remained at a high level in the vehicle-treated group, while in the SOD-treated group, the Ca2+ signal ratio decreased. There was a statistically significant difference between the two groups at 10, 20, and 30 min after reperfusion (p less than 0.01). The histologically damaged area in the SOD-treated group was significantly smaller than that in the vehicle-treated group (p less than 0.01). These data suggest that the histoprotective action of SOD may be due to its ability to attenuate increases in intracellular calcium during the recirculation period following focal cerebral ischemia.
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PMID:Effect of superoxide dismutase on intracellular calcium in stroke. 172 42

One hour after orthotopic rat liver transplantation, hepatic microcirculation and adhesion characteristics of leukocytes to the endothelial wall were studied with intravital microscopy. Cold storage for 1 and 8 hours in Euro-Collins solution resulted in reduction of perfused sinusoids to 83% and 48% and a decrease of leukocyte velocity from 417 microns/sec in controls to 311 microns/sec and 269 microns/sec, respectively. Additionally, the number of permanently adherent leukocytes rose from 4% in controls to 33% and 43% after cold storage for 1 and 8 hours. Intravenous injection of the free radical scavenger human recombinant superoxide dismutase (40 mg/kg) during reperfusion resulted in marked improvement of the hepatic microcirculation after both 1 and 8 hours of cold storage (91% and 69% perfused sinusoids; 420 microns/sec and 350 microns/sec leukocyte velocity; p less than 0.05). Furthermore, the percentage of permanently adherent leukocytes decreased to 13% and 28% after 1 and 8 hours of cold ischemia, respectively. These results support the hypothesis that oxygen-derived free radicals contribute to leukocyte adherence and microcirculatory failure after cold liver ischemia and transplantation. Thus, application of oxygen free radical scavengers during liver transplantation procedures might be useful to improve graft function.
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PMID:Reduction by superoxide dismutase of leukocyte-endothelial adherence after liver transplantation. 172 81

This study was designed to probe the hypothesis that oxygen-derived free radicals are involved in initiation of the no-reflow phenomenon. We developed a reproducible model of no reflow in the rat hind limb. Laser Doppler studies confirmed that the hind limbs perfused well after 2 or 4 hours of ischemia, but perfusion ceased in the first 10 minutes after 6 hours of ischemia. Venous blood samples and biopsy specimens of skin and muscle were taken after 2 and 4 hours of ischemia to study tissue injury. Blood samples were evaluated for xanthine oxidase (XO), xanthine dehydrogenase, and creatine phosphokinase (CPK) activities. Conjugated dienes and iodine 125-labeled albumin extravasation were quantified in tissue samples. Groups of animals were treated with inhibitors of XO (allopurinol), antioxidant enzymes (superoxide dismutase plus catalase), and free radical scavengers (dimethyl sulfoxide and dimethyl thiourea) to assess the roles of free radicals in ischemia-reperfusion injury in the hind limbs. After 4 hours of ischemia followed by reperfusion, plasma XO activity rose threefold over preischemia levels (p less than 0.05). Xanthine dehydrogenase activity did not change; conjugated diene levels in muscle rose twofold; CPK levels rose sixfold, and 125I albumin extravasation rose twofold (p less than 0.05). Pretreatment with the XO inhibitor allopurinol reduced XO activity to negligible levels and significantly attenuated conjugated diene levels, CPK levels, and albumin extravasation. Albumin extravasation was also significantly attenuated by pretreating animals with superoxide dismutase together with catalase, dimethyl thiourea, and dimethyl sulfoxide. In all animals pretreated with allopurinol or superoxide dismutase and catalase, reperfusion persisted after 6 hours of ischemia. These data suggest that, in ischemia followed by reperfusion, tissue injury is related to oxygen products derived from XO activity.
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PMID:Xanthine oxidase: its role in the no-reflow phenomenon. 173 87

Renal artery occlusion (RAO) for 30, 60 or 90 sec was found to reduce norepinephrine tissue levels in both the cortex and medulla of the rat, respectively, by 2 to 5%, 56 to 65% and 92 to 97%, but no significant change in dopamine tissue levels was found to occur. Similar effects were obtained with occlusion of the aorta proximally to the renal arteries for 90 sec. Administration of superoxide dismutase (40 mg/kg) immediately before RAO resulted in a marked protection of the norepinephrine depletion effect as caused by transient ischemia. The sodium-dependent formation of dopamine and 3,4-dihydroxyphenylacetic acid, the deaminated metabolite of dopamine, in renal slices loaded with L-3,4-dihydroxyphenylalanine (50 microM) was found to be similar in denervated and control kidneys. Type A and B monoamine oxidase activities were measured with the deamination of two specific substrates, respectively, [3H]-5-hydroxytryptamine and [14C]-beta-phenylethylamine, in homogenates of the renal cortex and renal medulla; neither type of monoamine oxidase, A or B, was found to be affected by denervation. The renal tissues collected for morphological observation were those in which RAO was performed for 90 sec. The general structure of the renal cortex was not affected by RAO, being similar in the control and the denervated kidney. In conclusion, the results presented suggest that the tissue damaging effect produced by RAO appears to be selective for the renal sympathetic innervation and seems to involve the generation of some reactive oxygen species, namely superoxide.
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PMID:Brief transient ischemia induces long-term depletion of norepinephrine without affecting the aromatic amino acid decarboxylase and monoamine oxidase activities in the rat kidney. 173 31


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