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)

Nitric oxide (NO) was measured directly after spinal cord injury (SCI) in rats by an ESR spin-trapping technique using Fe2+ and diethyldithiocarbamate (DETC). The levels of NO and lipid peroxides expressed as thiobarbituric acid reactive substances (TBARS) were increased by SCI in the injured region and the adjacent central region. Pretreatment with 30 mg/kg of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of NO synthase, accelerated increases of the TBARS level and myeloperoxidase (MPO) activity in the injured tissue and caused deterioration of hind limb motor function after SCI, suggesting that NO formation by constitutive NO synthase (c-NOS) has a protective effect against cellular damage resulting from ischemia-reperfusion after SCI. Though c-NOS mRNA expression was not altered after SCI, inducible NO synthase (i-NOS) mRNA expression increased to a maximum of 24 h after SCI with progress of motor dysfunction. Intravenous injection of L-NAME (0.1 mg/kg) 6, 24, 48, and 72 h after SCI reduced the motor disturbance. These results indicate that NO induced by i-NOS may be neurotoxic in the subacute phase after SCI.
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PMID:Roles of nitric oxide in compression injury of rat spinal cord. 890 74

We describe real-time measurement of myocardial oxygen consumption during ischemia in the intact heart. Measurement of extracellular oxygen concentration during myocardial ischemia by spin label oximetry has been limited by ischemia-induced reduction of the neutral, water-soluble nitroxide TEMPONE. We have overcome this problem by encapsulating the nitroxides. Isolated immature (7-10 d old) rabbit hearts (n = 8) were perfused aerobically within the cavity of a loop gap resonator with bicarbonate buffer containing an oxygen-sensitive, lipid-soluble nitroxide (14N-TEMPO laurate in FC-43 perfluorocarbon micelles) and a much less oxygen-sensitive and positively charged nitroxide (15N-TEMPO choline in multilamellar vesicles) as an internal standard. The ratio of the ESR signal amplitudes of these nitroxides was used as a sensitive index of oxygen concentration. Sequestration of the nitroxides decreased their reduction rate by ascorbate in comparison with nonsequestered nitroxides. Hearts were subjected to 60 min of global no-flow ischemia at 20 degrees C. Extracellular oxygen content (mean +/- SD) during aerobic perfusion was 1195 +/- 55 mumol/liter. The electron spin resonance signal from TEMPO laurate increased with the onset and progression of ischemia, consistent with a decrease in extracellular oxygen, while the signal for TEMPO choline was relatively unchanged. Extracellular oxygen content after 40 and 60 min of ischemia was reduced to 393 +/- 27 mumol/liter (p < .05) and 61 +/- 5 mumol/liter (p < .05), respectively. We conclude that spin-label oximetry can directly and precisely measure myocardial oxygen consumption at constant temperature during ischemia in the intact heart.
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PMID:Spin label oximetry to assess extracellular oxygen during myocardial ischemia. 895 35

Reactive oxygen metabolites (ROM) have been reported to be important in the pathogenesis of ischemia/ reperfusion-, ethanol-, nonsteroidal antiinflammatory drug-, or Helicobacter pylori-induced gastric mucosal injury. Rebamipide, a novel antiulcer agent, has been reported either to prevent various acute experimental gastric mucosal lesions or to accelerate the healing of chronic gastric ulcers. The underlying mechanism by which rebamipide exerts its cytoprotective effect in the damaged stomach is not fully determined. We investigated the role of rebamipide in protecting against ROM-mediated cell damage in gastric mucosal cells and in inducing cytoprotective proteins. Cells were exposed to ROM enzymatically generated by hypoxanthine-xanthine oxidase. Cytotoxicity was quantified by measuring specific 51Cr release from prelabeled cells. ROM caused dose-dependent increase in cytotoxicity and amount of thiobarbituric acid-reactive substances (TBA-RS). ROM-induced cytotoxicity and TBA-RS were dose-dependently decreased by the addition of rebamipide and/or catalase, but not by superoxide dismutase alone. The effects of rebamipide on electric spin resonance signal were investigated. We found that the DMPO spin adduct ESR signal of hydroxyl radicals (DMPO-OH) was significantly attenuated by rebamipide. Western blot analysis showed that induction of heat-shock protein (HSP70) was significantly increased following rebamipide administration in a dose-dependent manner. Based on these results, it is concluded that rebamipide exerted a protective effect on HX-XO-induced gastric mucosal cell cytotoxicity through one or more of the following mechanism(s): (1) inhibition of lipid peroxidation of the cell membrane; (2) hydroxyl radical scavenging activity; and (3) induction of cellular cytoprotective protein such as HSP70.
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PMID:Role of rebamipide on induction of heat-shock proteins and protection against reactive oxygen metabolite-mediated cell damage in cultured gastric mucosal cells. 901 34

In recent years there has been considerable interest concerning the role of hepatocellular Ca2+ overload which probably was a major factor in hepatic ischemia/reperfusion injury. We studied the effect of radix salviae miltiorrhizae (RSM) on cytosolic free calciumion concentration [(Ca2+)i](nM) in isolated hepatocytes in rats and patients with ischemia reperfusion by microflurometry using fluorescent (Ca2+)i indicator Fura-2/AM. Changes of lipid peroxide free radical (ROO.) signal ranges with in the liver tissue by ESR technique and those of hepatocellular ultrastructure by electronmicroscope were also observed. The results showed that RSM reduced levels of (Ca2+)i and ROO. Ymax (mm) ESR signal rangs. RSM had an effect on protecting hepatocytes against ischemia/reperfusion injury as a useful receptor-operated calcium channels (ROC) blocker.
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PMID:[An experimental and clinical study on radix Salviae miltiorrhiae in the treatment of hepatocellular Ca2+ overload during hepatic ischemia/reperfusion injury]. 938 33

1. In nonanesthetized rabbits temporal occlusion of the abdominal aorta was used to induce oxidative stress in the lower part of the body including distal segments of the spinal cord. 2. Spinal cord samples were taken from the animals exposed to 25-min aortic occlusion (AO) or to occlusion followed by 1- or 2-hr reperfusion (AO/R1 or AO/R2, respectively) or from sham-operated animals (C). The presence of free radicals (FR) in the spinal cord samples frozen in liquid N2 was assessed by ESR spectroscopy without spin trapping. Moreover, superoxide dismutase (SOD) activity and conjugated diene (CD) levels were measured in the samples. 3. In the AO group FR were detected in the spinal cord regions close to the occlusion (lower thoracic and distal segments) along with a decrease in SOD activity. The calculated g value (g = 2.0291) indicated that the paramagnetic signal recorded might be attributed to superoxide radicals. FR were absent in the AO/R1 group. Concurrently, the SOD activity revealed a significant tendency to return to the control level. FR appeared again in the AO/R2 group, mostly in the upper and middle lumbar regions, along with a decrease in SOD activity. No sample from the C group revealed FR. A significant increase in CD levels was observed in the thoracolumbar region only in the AO/R2 group. The temporary absence of FR in the AO/R1 group suggests activation of defense antioxidant mechanisms (e.g., specific enzymatic systems such as SOD), which might have been exhausted later. 4. Changes in SOD activity similar to those observed in the thoracolumbar region, though less noticeable, occurred in the obviously noncompromised tissue (upper cervical region). This points to a kind of generalized response of the animal to aortic occlusion. 5. Direct ESR spectroscopy revealed the presence of FR as well as their time course in the spinal cord during the early phase of ischemia/reperfusion injury and the inverse relationship between FR and SOD activity.
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PMID:Free radicals in rabbit spinal cord ischemia: electron spin resonance spectroscopy and correlation with SOD activity. 961 95

Formation of free radicals during reperfusion of the isolated ischemic heart has often been demonstrated by detecting hydroxyl radical spin adducts of the nitrone 5,5-dimethyl-1-pyrroline N-oxide (DMPO) in coronary effluents. However, questions still remain regarding (a) whether the reported cardiovascular effects of nitrone perfusion may affect the formation of spin adducts, and (b) the primary generation of superoxide (O2.-), because of the short persistency of O2.-/DMPO spin adduct. We therefore compared the effects of perfusing 5 mM of two nitrones, DMPO and 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO) or the two structurally related pyrrolidines, diethyl (2-methyl-2-pyrrolidinyl) phosphonate (DEPMPH) and pyrrolidine (PyH), on postischemic functional recovery of rat hearts subjected to 10 min of low-flow ischemia, 30 min of global ischemia and 60 min of reperfusion. All compounds were added to the perfusate before ischemia, throughout low-flow ischemia and during the initial 10 min of reflow. In one additional group, hearts received DEPMPO only at reflow. Hemodynamic and in vitro ESR evidence is presented indicating that the phosphonate group of DEPMPO and DEPMPH confers these molecules with an enhanced cardioprotective efficacy, unrelated to radical scavenging, acting in synergy with the intrinsic radical trapping effects of the nitronyl group. Continuous-flow ESR spin trapping using 5.7 mM DEPMPO administered at reflow, but not before ischemia, demonstrated for the first time extended formation of O2.- in the reperfused myocardium.
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PMID:Nitrone spin traps and their pyrrolidine analogs in myocardial reperfusion injury: hemodynamic and ESR implications--evidence for a cardioprotective phosphonate effect for 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide in rat hearts. 966 Jan 78

The ESR signal of NO bound to hemoglobin was detected during the ischemia-reperfusion of myocardium with low temperature ESR technique, and the synergic effects of NO and oxygen free radicals in the injury of the process were studied with this technique. Oxygen free radicals and NO bound to beta-subunit of hemoglobin (beta-NO complex) could be detected simultaneously in the ischemia-reperfused myocardium. Those signals could not be detected from the normal myocardium even in the presence of L-arginine. However, those signals could be detected and were dose-dependent with L-arginine in the ischemia-reperfused myocardiums and the signal could be suppressed with the inhibitor of NO synthetase, NG-nitro-L-arginine methylester (NAME). Measurement of the activities of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary artery effluent of ischemia-reperfused heart showed that L-arginine at lower concentration (< 1 mmol/L) could protect the heart form the ischemia-reperfusion injury but at higher concentration aggravate the injury. Addition of NAME to the reperfusion solution could also protect the myocardium. Addition of xanthine (X)/xanthine oxidase (XO) or Fe2+/H2O2 to the reperfusion solution increased the production of NO and oxygen free radicals and the ischemia-reperfused injury simultaneously. Addition of superoxide dismutase (SOD) and catalase decreased the production of NO and oxygen free radicals and the ischemia-reperfusion injury.
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PMID:Synergic effects of NO and oxygen free radicals in the injury of ischemia-reperfused myocardium--ESR studies on NO free radicals generated from ischemia-reperfused myocardium. 977 52

Post-ischemic reperfusion causes cardiac dysfunction and radical-induced lipid peroxidation (LPO) detectable by ESR spin trapping. This study deals with the applicability of the spin trapping technique to pharmacological investigations during myocardial reperfusion injury. The use of the spin trap phenylbutylnitrone (PBN, 3 mM) in isolated rat hearts demonstrated the release of alkoxyl radicals (aN = 1.39 mT, aHbeta = 0.19 mT) formed particularly within the first 15 min of reperfusion following 30 min of ischemia. The decline of radicals, after 10 min of reperfusion, was accompanied by recovery of function in 80% of the hearts. The radical concentration in the coronary effluent (maximum after 7.5 min) was reduced by the infusion of 1 mM mercaptopropionylglycine (MPG, 2.7+/-0.5 U/ml, p < 0.001) or 5 microM vitamin E (11.7+/-0.8 U/ml, p < 0.001), compared to the (PBN-containing) control (29.7+/-4.3 U/ml). Moreover, functional recovery (left ventricular developed pressure, LVDP 91.6 +/-20% of pre-ischemic level, p < 0.05) was improved by the hydrophilic radical scavenger MPG, compared to the (PBN-containing) control (LVDP 50.5+/-15.7% of baseline). PBN alone led to higher functional recovery (p < 0.05) and reduced VF (duration of ventricular fibrillation; 7.10+/-0.36 min/30 min, p < 0.05), compared to the untreated (PBN-free) control (LVDP 26.6+/-11.8%; VF 19.42+/-3.64 min/30 min). The Ca antagonist verapamil (0.1 microM), MPG, and the lipophilic vitamin E showed cardioprotection in the absence of PBN: post-ischemic recovery of LVDP was 25.4+/-6.8% (p < 0.05), 39.6+/-12.7% (p < 0.05) and 52.4+/-2.6% (p < 0.01), respectively, compared to the corresponding untreated control (13.3+/-6.6%). Whereas verapamil and vitamin E were able to protect the heart when present alone, they offered no additive effect in the presence of PBN. Therefore, PBN can be used to estimate the radical scavenger properties of an agent in the heart. However, because of the protective properties of PBN itself, the results of simultaneous investigations of the effects of other compounds, such as Ca antagonists or lipophilic radical scavengers, on heart function may be limited.
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PMID:PBN spin trapping of free radicals in the reperfusion-injured heart. Limitations for pharmacological investigations. 977 91

The effect of various organic acids on hydroxyl radical (.OH) generation in the Fenton reaction were examined by the ESR spin trapping technique, where 5,5-dimethyl-1-pyroline-N-nitroxide (DMPO) and alpha-phenyl-tert-butyl nitrone (PBN) were used as the spin trapping reagents. alpha-Hydroxy acids such as lactic acid, glycolic acid and 2-hydroxy isobutyric acid were found to markedly enhance .OH generation in the reaction. In contrast, beta-hydroxy acid, alpha-keto acid, esters of alpha-hydroxy acids, aldehydes and other straight chain organic acids had no such enhancing activity. alpha-Amino acids had also no enhancing effect. The results suggest that the alpha-hydroxy acid moiety is prerequisite for the enhancement of .OH generation in the Fenton reaction. Superoxide dismutase did not inhibit the enhancing effect of alpha-hydroxy acids whereas catalase completely inhibited the .OH generation. Thus, alpha-hydroxy acids directly enhanced the .OH generation via the Fenton reaction but not the Haber-Weiss reaction. Possible role of lactic acid manipulating .OH generation is discussed in relation to the ischemia-reperfusion cell damage.
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PMID:Enhancement of hydroxyl radical generation in the Fenton reaction by alpha-hydroxy acid. 978 48

The effect of ad libitum oral-administration of (-)catechin solution on ischemia-reperfusion-induced cell death of hippocampal CA1 in the gerbil was histologically examined. When (-)catechin solution instead of drinking water was orally administered ad libitum for 2 weeks, dose-dependent protection against neuronal death following by transient ischemia and reperfusion was observed. To evaluate the involvement of reduction of reactive-oxygen-species (ROIs) by the antioxidant activity of (-)catechin in this protection, the superoxide scavenging activity of the brain in catechin-treated gerbils was measured by ESR and spin-trapping using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The superoxide scavenging activities of the brains obtained from catechin-treated gerbils were significantly higher than those of catechin-untreated animals. From these results, it was suggested that orally administered (-)catechin was absorbed, passed through the blood-brain barrier and that delayed neuronal death of hippocampal CA1 after ischemia-reperfusion was prevented due to its antioxidant activities.
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PMID:Oral administration of (-)catechin protects against ischemia-reperfusion-induced neuronal death in the gerbil. 986 51


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