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

Experiments were performed to investigate the effects of 60 min severe global ischemia followed by 30 min reperfusion on the antioxidant enzymatic system in the isolated perfused rat heart. Ischemia induced a significant increase of cytoplasmic and mitochondrial selenium-dependent glutathione peroxidase (EC 1.11.1.9) activity. In reperfused hearts, only the mitochondrial form showed a further significant increase. Glutathione reductase (EC 1.6.4.2) was increased in ischemic hearts, whilst the reperfused hearts showed a decrease towards the level found in aerobic hearts. Mitochondrial superoxide dismutase (EC 1.15.1.1) activity was depressed in ischemic as well as in reperfused hearts, though the cytoplasmic form was unmodified. Catalase (EC 1.11.1.6), glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and glutathione transferase (EC 2.5.1.18) activities were unchanged throughout the experiment. Ischemia and reperfusion induced a significant fall in tissue-reduced glutathione content concomitant with an increase of its oxidized form. We have also studied the mitochondrial inner membrane proteins for both molecular weight, with Coomassie blue, and thiol status, with monobromobimane stain, using a sodium dodecyl sulfate polyacrylamide gel electrophoresis technique. Neither ischemia nor reperfusion effected any relevant modification of the molecular weight of the mitochondrial inner-membrane proteins either in the presence or absence of a reducing agent. However, two of these proteins with an apparent molecular weight of 52,0000 and 12,000 showed a decrease in the monobromobimane stain, probably due to the oxidation of their thiol groups.
 ...
PMID:Effect of ischemia and reperfusion on antioxidant enzymes and mitochondrial inner membrane proteins in perfused rat heart. 338 95

Pretreatment of animals with certain antioxidant enzymes and substances decreases renal damage following ischemia and reperfusion. The hypothesis that reoxygenation imposes an oxidant stress has been used to explain this. The present study has directly assessed oxidant stress under these conditions by measuring the glutathione redox ratio ([GSSG/(GSH + GSSG)] x 100) in freeze-clamped kidney. The glutathione peroxidase system plays a role in removing peroxides which result from oxidant stress, generating GSSG from GSH in the process. The selenium-dependent glutathione peroxidase can metabolize H2O2 and other hydroperoxides. A non-selenium-dependent glutathione peroxidase activity is present and can metabolize organic hydroperoxides, but it cannot metabolize H2O2. Under anesthesia, the left renal artery was occluded for 40 minutes and then reflow was allowed. Kidneys were freeze clamped before reflow and after 5, 10, and 15 minutes of reflow. The contralateral kidney was freeze clamped and used as a control. The control value for the glutathione redox ratio was 1.09 +/- 0.05. This fell during ischemia to 0.67 +/- 0.22 and increased significantly to 1.66 +/- 0.29 after five minutes of reperfusion. By 15 minutes it had returned to 1.09 +/- 0.22. Treatment of rats with diquat, which causes a severe oxidant stress, raised the glutathione redox ratio from 0.88 +/- 0.12 to 1.89 +/- 0.15. Thus, reperfusion was concluded to cause a large but transient oxidant stress. Selenium-deficient rats were used to examine the nature of the oxidant stress. Activity of the selenoenzyme glutathione peroxidase was depressed to 2% of control in the kidneys of these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Oxidant stress following renal ischemia: changes in the glutathione redox ratio. 338 35

In 1969 McCord and Fridovich discovered superoxide dismutase, which converts the oxygen free radical O(2) (-) to hydrogen peroxide H(2)O(2). In the presence of excess O(2) (-), H(2)O(2) may then undergo further reduction to the highly toxic hydroxyl radical, OH(*). Since the description of this enzymatic process, there has been explosive growth in related biochemical research, which has now percolated through to clinical investigation. The hypoxanthine-xanthine oxidase system originally used as a radical production model has a close counterpart in the ischemia-reperfusion phenomenon purported to cause diseases of heart, brain and gastrointestinal tract, and free radicals are now known to have a critical role in postphagocytic bacterial killing. Prototypic deficiency diseases such as chronic granulomatous disease are now recognized. Some evidence indicates that excess states such as perhaps Batten's disease also occur, and environmental influences such as selenium and vitamin E deficiency may augment free radical levels. Many disorders including microvasculopathies, noncardiogenic pulmonary edema, glomerulopathies and radiation damage may owe part of their proximate pathogenesis to free radicals. Control of tissue free radical levels is now pharmacologically feasible and perhaps justified for specific diseases.
 ...
PMID:The expanding role of oxygen free radicals in clinical medicine. 352 Oct 94

A large amount of biochemical, physiological, and pharmacological data has been obtained which supports a mechanistic role of oxygen free radical-induced lipid peroxidation (LP) in post-traumatic spinal cord degeneration. Biochemical evidence of early and progressive lipid peroxidative reactions occurring in the injured spinal cord includes: an increase in polyunsaturated fatty acid peroxidation products (e.g., malonyldialdehyde), a decrease in cholesterol and the appearance of cholesterol oxidation products, an increase in cyclic GMP presumably due to free radical activation of guanylate cyclase, a decrease in tissue anti-oxidant levels (e.g., alpha tocopherol, reduced ascorbate), and inhibition of membrane-bound enzymes such as Na+ + K+-ATPase. In vitro CNS tissue studies have provided support for the possibility that LP may contribute to other early post-traumatic events including intracellular calcium accumulation and arachidonic acid release. Moreover, spinal tissue lactic acidosis, which occurs early after injury, can exacerbate LP reactions. The involvement of LP in the development of progressive post-traumatic spinal white matter ischemia has been strongly inferred from pharmacological studies in cats with known inhibitors of LP. For example, the dose-response curves for the ability of the glucocorticoid methylprednisolone (MP) to inhibit post-traumatic LP and to retard ischemia development are identical. This relationship between LP and post-traumatic ischemia is more directly implied from studies showing that pretreatment of cats with high doses of anti-oxidants (e.g., d-alpha tocopherol plus selenium p.o. or 1-ascorbic acid i.v.) can also significantly antagonize the progressive decrease in spinal cord blood flow that follows severe blunt injury. However, a similar efficacy of certain calcium and prostaglandin antagonists suggests an interrelationship between aberrant calcium fluxes, vasoconstrictor/platelet aggregating prostanoids, and LP in the post-traumatic ischemic phenomenon. In addition to a role of LP in ischemia development, the action of intensive d-alpha tocopherol and selenium pretreatment to retard anterograde cat motor nerve fiber degeneration after nerve section suggests that LP may also be a fundamental mechanism of "Wallerian" axonal degeneration after neural injury. Finally, a critical role of LP in the acute pathophysiology of CNS injury in general has been supported by the finding of an excellent correlation, in terms of efficacy and potency, between the action of glucocorticoid and nonglucocorticoid steroids to inhibit neural tissue LP in vitro and to promote early neurological recovery in severely head-injured mice.
 ...
PMID:Role of lipid peroxidation in post-traumatic spinal cord degeneration: a review. 355 50

Compression trauma of the cat spinal cord induces a very rapid alteration in the lipid metabolism of cellular membranes, including lipid hydrolysis with release of fatty acids including arachidonate, production of biologically active eicosanoids, and loss of cholesterol. This disturbance of cellular membranes can directly damage cells and can lead to the secondary development of tissue ionic imbalance, ischemia, edema, and inflammation with neuronophagia. Pretreatment with either the synthetic glucocorticoid methylprednisolone sodium succinate (MPSS) or the antioxidants vitamin E and selenium (Se) completely prevented the loss of cholesterol and partially inhibited lipolysis and prostanoid production. Treatment with MPSS significantly reduced the postinjury tissue necrosis and paralysis. Preliminary evidence indicates that pretreatment with vitamin E and Se also protected against the effects of spinal cord injury (SCI). We speculate that the ability of these agents to preserve function after SCI may, in part, reside in their capacity to limit the trauma-induced changes in lipid metabolism.
 ...
PMID:Lipid hydrolysis and peroxidation in injured spinal cord: partial protection with methylprednisolone or vitamin E and selenium. 383 12

Subsequent to traumatic injury of the spinal cord, a series of pathophysiological events occurs in the injured tissue that leads to tissue destruction and paraplegia. These include hemorrhagic necrosis, ischemia, edema, inflammation, neuronophagia, loss of Ca2+ from the extracellular space, and loss of K+ from the intracellular space. In addition, there is trauma-initiated lipid peroxidation and hydrolysis in cellular membranes. Both lipid peroxidation and hydrolysis can damage cells directly; hydrolysis also results in the formation of the biologically active prostaglandins and leukotrienes (eicosanoids). The time course of membrane lipid alterations seen in studies of antioxidant interventions suggests that posttraumatic ischemia, edema, inflammation, and ionic fluxes are the result of extensive membrane peroxidative reactions and lipolysis that produce vasoactive and chemotactic eicosanoids. A diverse group of compounds has been shown to be effective in ameliorating spinal cord injury in experimental animals. These include the synthetic glucocorticoid methylprednisolone sodium succinate (MPSS); the antioxidants vitamin E, selenium, and dimethyl sulfoxide (DMSO); the opiate antagonist naloxone; and thyrotropin-releasing hormone (TRH). With the exception of TRH, all of these agents have demonstrable antioxidant and/or anti-lipid-hydrolysis properties. Thus the effectiveness of these substances may lie in their ability to quench membrane peroxidative reactions or to inhibit the release of fatty acids from membrane phospholipids, or both. Whatever the mode of action, early administration appears to be a requirement for maximum effectiveness.
 ...
PMID:Spinal cord injury and protection. 392 95

The radical anions of molecular oxygen reduction, superoxide (O2), hydrogen peroxide (H2O2), and hydroxyl radical (OH), have been implicated in a number of disease processes, including ischemic bowel injury. This report evaluates the effect of superoxide dismutase (SOD), catalase (CAT), dimethyl sulfoxide (DMSO), selenium treatment, and selenium deficiency on bowel integrity and survival in experimental intestinal ischemia in rats. Ischemic bowel injury was produced in 204 male Sprague-Dawley rats (wt 90 to 100 g) by a one-minute occlusion of the superior mesenteric artery (SMA) with a microaneurysm clip. Experiment I treatment animals (n = 20) received 2.5 mg/kg SOD dissolved in Ringer's lactate, and control animals (n = 71) received Ringer's lactate alone. Experiment II treatment animals (n = 16) received 1 cc of 100% DMSO gavage, and control animals (n = 11) received no treatment. Experiment III treatment animals (n = 17) received 25 mg/kg CAT dissolved in phosphate buffered saline, and control animals (n = 11) received nothing. Experiment IV treatment animals (n = 14) received 300 micrograms of sodium selenate by gavage dissolved in deionized water, and control animals (n = 15) receiving nothing. Experiment V treatment animals (n = 20) were raised from 35 to 50 g size on a selenium deficient diet, and control animals were raised (n = 20) on a normal rat chow diet, until they weighed 100 g when ischemia was induced. At seven days, survival, incidence of bowel perforation or necrosis, and length of survival were compared in each experiment between control and treatment groups using chi 2 analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Superoxide: a critical oxygen-free radical in ischemic bowel injury. 609 60

The heart is the most susceptible of all the organs to premature aging and free radical oxidative stress. Clinical research has clearly documented the role of free radical damage and the progression of numerous degenerative diseases, particularly cardiovascular disease. This may be the result of acute ischemia-reperfusion injury, endothelial damage of hyperhomocysteinemia, as well as chronic oxidative damage secondary to lipid peroxidation. Fortunately, although highly responsive, and therefore vulnerable to the effects of oxidative stress, the heart is also receptive to the benefits of targeted phytonutrients, antioxidants, and nutritionals. The effects of antioxidant nutrients have been extensively evaluated in epidemiological, population, and clinical studies. Phytonutrients such as the natural flavonoids and carotenoids found in fresh fruits and vegetables or vitamins C, E, and beta-carotene have powerful antioxidant effects. In addition, minerals like selenium and nutrients such as coenzyme Q10 will minimize free radical risk and optimize a favorable outcome from the ubiquitous presence of oxidative stress on the cardiovascular system. The B complex, particularly folic acid, B12, and B6 are also essential in the prevention of hyperhomocysteinemia, another major risk factor for the circulatory system. Measures to minimize accumulation of heavy metals in the body, especially iron and copper, which are capable of initiating adverse free radical reactions, will also help to assuage oxidative stress. Thus, the combination of a healthy diet supplemented with antioxidants and phytonutrients may be useful in the prevention and promotion of optimum cardiovascular health.
 ...
PMID:Free radicals, oxidative stress, oxidized low density lipoprotein (LDL), and the heart: antioxidants and other strategies to limit cardiovascular damage. 758 73

Selenium (Se) is an integral component of glutathione poeroxidase (GSHPx), and the serum selenium concentration is age-depend. We speculated that myocardial GSHPx had relation to reperfusion injury in open heart operations, especially in infants in whom GSHPx activity is low. This study correlated GSHPx activity with the serum and myocardial selenium concentrations in Wistar rats, which were divided into three groups, infants, Se-deficient rats, and control rats. Serum GSHPx activity in infant and Se-deficient rats (22.7 +/- 3.5 U/g protein, 24.6 +/- 22.2 U/g protein) was lower than that in controls (179 +/- 12.0 U/g protein). The serum selenium concentration in infant and Se-deficient rats (3.81 +/- 0.81 micrograms/g protein, 2.06 +/- 1.69 micrograms/g protein) was also lower than that in controls (7.32 +/- 2.96 micrograms/g protein). The myocardial GSHPx activity was significantly lower in infants and Se-deficient rats (4.76 +/- 1.05 x 10(-1) U/mg protein, 3.38 +/- 0.32 x 10(-1) U/mg protein) than that in controls (8.03 +/- 0.57 x 10(-1) U/mg protein). However, the myocardial selenium concentration in infants (1.42 +/- 0.24 x 10(-1) micrograms/mg protein) was significantly higher than that in the other groups (0.31 +/- 0.06 x 10(-1) micrograms/mg protein, 0.28 +/- 0.04 x 10(-1) micrograms/mg protein). Next, in Se-deficient and control rats, isolated hearts were perfused for aerobically with Krebs-Henseleit solution in the Langendorff mode for 15 minutes, followed by 60 minutes of global ischemia at 4 degrees C and then reperfused for 30 minutes in a working mode. The hemodynamic parameters were measured.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The significance of glutathione peroxidase on myocardial protection in the rat hearts: the key of clarify the cause of vulnerability to reperfusion injury in infantile cardiac operations. 772 11

Circulatory shock and its treatment have been compared to a whole-body ischemia and reperfusion with activation of oxygen-derived free radicals. A pilot study had suggested a selenium redistribution in this context. To verify this hypothesis, an experimental study was designed. Temporary occlusion of the superior mesenteric artery was performed in 18 male adult Wistar rats using clamping for 0, 10, and 20 min. Hemodynamic and biochemical data were assessed before clamping and 20 min after release of the mesenteric blood flow. After release, mean arterial pressure decreased, plasma lactate increased, and erythrocyte glutathione peroxidase decreased. Plasma and erythrocyte selenium did not change; however, a slight decrease in plasma selenium was observed when related to hematocrit (to take into account the fluid balance). Erythrocyte-reduced glutathione did not change. In contrast, liver and kidney selenium increased, whereas reduced glutathione decreased in kidney, but not in liver after 20 min of clamping as compared to the sham-operated group. These results suggest that, after temporary intestinal ischemia, the changes in selenium and reduced glutathione observed in blood and tissues, like liver or kidney, could be related to a redistribution pattern in selenium metabolism during shock injury.
 ...
PMID:Selenium, oxygen-derived free radicals, and ischemia-reperfusion injury. An experimental study in the rat. 777 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>