Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00568 (ascorbate)
 23,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was shown that when injected into a suspension of sarcoplasmic reticulum (SR) vesicles phosphatidyl ethanol-amine hydroperoxide (HP) slightly activated Ca++-dependent ATPase and increased the permeability of SR membranes for Ca++ during the enzyme function. Linoleic acid HP had no effect on the parameters of the enzymatic Ca++- transporting system (activity of Ca++-dependent ATPase, Ca/ATP ratio, rate of Ca++ efflux) in the SR membranes due to its insufficient incorporation into the SR fragments. It is concluded that among the primary molecular products of lipid peroxidation (free fatty acid HP, phospholipid HP) induced both in vitro (by the Fe++ + ascorbate system) and in vivo (ischemia, E-avitaminosis), only the phospholipid HPs were modifiers of Ca++ transport in the SR membranes.
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PMID:[Disruption of the Ca++ transport enzyme system in sarcoplasmic reticulum membranes upon exposure to phospholipid hydroperoxides and fatty acid hydroperoxides]. 15 51

Antioxidant properties of thioctic and dihydrolipoic acid have been demonstrated in membranes and low density lipoproteins (LDL) in vitro. In vivo studies with dietary supplementation of thioctic acid to rats showed that it can also protect tissues against oxidative damage. Presumably, this action is due to a thioctic acid dihydrolipoic acid (TA/DHLA) coupled antioxidant mechanism, which enhances the activity of other antioxidants (i.e. ascorbate, alpha-tocopherol) by regenerating them from their radical form. In the present study, thioctic acid proved to protect against ischemia/reperfusion injury to Langendorff perfused hearts. Hearts isolated from rats fed thioctic acid and subjected to ischemia exhibited better mechanical recovery (left ventricular developed pressure) after reperfusion and lower lactate dehydrogenase leakage. Thioctic acid supplementation also decreased the appearance of fluorescent lipid peroxidation products after ischemia/reperfusion, lowered the rate of 2,2'-azobis-(2,4-dimethylvaleronitrile) (AMVN) induced lipid peroxidation in heart homogenates, and prevented the loss of alpha-tocopherol. The total sulfhydryl group content in thioctic acid fed animals was higher and the decrease due to ischemia-reperfusion was not as marked in this group as observed in the control. These results show that dietary supplementation with thioctic acid in vivo provides protection against ischemia/reperfusion injury in the Langendorff heart model.
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PMID:Thioctic acid protects against ischemia-reperfusion injury in the isolated perfused Langendorff heart. 144 47

Restoration of coronary blood flow after myocardial ischemia is always a matter of urgency, but the resulting surgical or drug-induced reperfusion of ischemic tissue is often associated with myocardial functional disturbances and tissue injury. The present study was carried out to select experimental conditions under which optimal effects of antioxidants can be observed on the adverse effects of reperfusion of ischemic myocardium. The release of lactate dehydrogenase (LDH) and changes in hemodynamic parameters were compared in two models of cardiac reperfusion injury in rat isolated hearts. LDH release from electrically-stimulated hearts perfused under constant flow and with initial (5 min) reperfusion in calcium-free buffer was greater than that from hearts perfused under constant pressure in which ischemia was induced by reduced flow. Combined SOD+catalase was a weak inhibitor of LDH release in both models, ascorbic acid being more potent under constant pressure than under constant flow conditions. A longer ischemic period enhanced the inhibitory effect of ascorbate. Contractility and ventricular end-diastolic pressure recovered slowly during perfusion under constant flow and brief calcium removal, but remained unphysiological under constant pressure. SOD+catalase had no effect on hemodynamic parameters. Ascorbic acid exacerbated ischemia+reperfusion-induced changes in contractility, ventricular pressure, heart rate and coronary flow under constant pressure, but facilitated recovery of contractility on reperfusion under constant flow and brief calcium removal. In studies on antioxidants, different experimental conditions appear to be necessary to observe beneficial effects on tissue damage on the one hand and on hemodynamics on the other. Mild to moderate ischemia, with sustained pacemaker activity, appears to be the condition under which antioxidants provide hemodynamic improvement. In isolated rat hearts, biochemical parameters of tissue damage may be misleading for the effects of antioxidants.
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PMID:Experimental conditions determine effects of ascorbic acid on reperfusion injury: comparison of tissue damage with hemodynamic parameters in rat isolated hearts. 146 51

To assess whether oxidative stress contributes to the ischemia/reperfusion injury of aortic surgery, the contents of alpha-tocopherol, alpha-tocopheryl quinone, ascorbate, lipid-derived malondialdehyde, protein thiols, cholesterol, and lactate were analyzed in plasma samples from 24 patients subjected to aortic crossclamping. alpha-Tocopherol, ascorbate, and protein thiols decreased during ischemia, whereas alpha-tocopheryl quinone increased in all but two cases, doubling on average in proportion to alpha-tocopherol. Upon reperfusion alpha-tocopherol, ascorbate, and protein thiols remained low, whereas alpha-tocopheryl quinone returned to the preischemic level. Lipid-derived malondialdehyde (a measure of lipid hydroperoxides) increased significantly only during reperfusion. The results suggest that oxidative stress occurs simultaneously with ischemia/reperfusion during aortic surgery, and that measurement of the tocopheryl quinone/tocopherol ratio may shed new light on the underlying pathological events.
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PMID:Antioxidant depletion in aortic crossclamping ischemia: increase of the plasma alpha-tocopheryl quinone/alpha-tocopherol ratio. 151 43

When Trolox (a polar analog of vitamin E) is conjugated to p-aminophenyl-beta-D-lactopyranoside, the resulting lactosylphenyl Trolox becomes a markedly more stable and effective hepatoprotector than Trolox. In primary rat hepatocytes exposed to xanthine oxidase-hypoxanthine, lactosylphenyl Trolox prolonged cell survival better than did Trolox, mannitol or ascorbate. In rats that underwent 80-min partial hepatic ischemia, infusion of lactosylphenyl Trolox at 2.9 to 5.7 mumol/kg body wt just before reoxygenation salvaged the organ more extensively than did Trolox. Mechanistically, we showed (a) that lactosylphenyl Trolox does not inhibit xanthine oxidase; (b) that lactosylphenyl Trolox effectively scavenges oxyradicals generated with xanthine oxidase and the peroxyl radicals produced with 2,2'-azo-bis(2-amidinopropane) HCl; (c) that both in hepatocytes and in vivo, lactosylphenyl Trolox is distinctly more cytoprotective than either or both of its precursors; and (d) that lactosylphenyl Trolox is amphipathic (i.e., it has both hydrophilic and hydrophobic properties), which enable it to better access and protect the lipid and aqueous milieus of the cell than the lipophile vitamin E and the moderately polar Trolox. Thus there are strong fundamental reasons for lactosylphenyl Trolox being an effective antioxidant-based hepatoprotector.
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PMID:Enhancement in antioxidant-based hepatoprotective activity of Trolox by its conjugation to lactosylphenylpyranoside. 154 27

The cardioprotective effects of a high dose of ascorbate on ischemia-reperfusion-induced myocardial damage were investigated using open chest anesthetized dogs. Two-hour occlusion of the left anterior descending coronary artery (LAD) induced mitochondrial dysfunction with a depletion of mitochondrial glutathione (GSH) concentration. Two-hour LAD occlusion followed by 1-h reperfusion worsened the ischemia-induced mitochondrial dysfunction together with a marked depletion of mitochondrial GSH concentration. Ascorbate reduced the mitochondrial dysfunction and prevented the depletion of mitochondrial GSH concentration after 2-h LAD occlusion and 1-h reperfusion. Activities of mitochondrial glutathione peroxidase and glutathione reductase did not change significantly in each group. Administration of ascorbate also prevented reperfusion arrhythmias without affecting blood pressure or heart rate. These results suggest that coronary reperfusion induces mitochondrial dysfunction and a depletion of mitochondrial GSH concentration, and that a high dose of ascorbate prevents reperfusion damage.
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PMID:The effects of a high dose of ascorbate on ischemia-reperfusion-induced mitochondrial dysfunction in canine hearts. 158 8

Ascorbate (vitamin C) is believed to act as a neuromodulator that facilitates the release of neurotransmitters and inhibits neurotransmitter binding to receptors, including dopamine and N-methyl-D-aspartate receptors. Extracellular levels of ascorbate are known to reach the low millimolar range after ischemic brain injury. This study shows that treatment of cultured cortical neurons with micromolar to low millimolar ascorbate first inhibits total protein synthesis and then results in late neuronal death. Astrocytes are much less vulnerable to ascorbate than neurons. Ascorbate may exacerbate neuronal and glial damage after brain ischemia, and it may play a pathological role in other neurological diseases.
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PMID:Ascorbate neurotoxicity in cortical cell culture. 159 92

Isolated Langendorff-perfused rat hearts after 20 min of normoxic perfusion in the presence of 2.5 mM Ca++ and 11 mM glucose were subjected to 30 min of global normothermic ischemia followed by 30 min of normoxic reperfusion with the starting buffer. At the end of each perfusion condition, hearts were freeze-clamped and deproteinized by 0.6 M HClO4. Two-hundred microL of the neutralized tissue extracts were analyzed by a recently developed high-performance liquid chromatography (HPLC) method for the simultaneous determination of malondialdehyde (MDA), ascorbic acid, and adenine nucleotides. By means of this analytical technique, it was possible to demonstrate that MDA is undetectable in control hearts. In contrast, 30 min of ischemia induced a modest production of MDA (0.012 mumol/g dw), while a large amount of MDA (0.103 mumol/g dw) was observed in reperfused hearts. Values referring to ascorbic acid showed that the concentration of this antioxidant progressively decreased from 1.190 (control hearts) to 0.837 (ischemic hearts) and to 0.595 mumol/g dw (reperfused hearts). The overall conclusions of this study are that reperfusion induces an oxidative stress to the isolated myocardium, a decrease of ascorbate, and an increase of lipid peroxidation. Therefore, by means of a proper analytical method, MDA may represent a valid biochemical parameter to demonstrate the relationship between myocardial reperfusion and a detectable tissue damage.
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PMID:Malondialdehyde production and ascorbate decrease are associated to the reperfusion of the isolated postischemic rat heart. 162 55

Reperfusion injury of ischemic organs is suggested to result from metabolic derangements initiating an imbalanced formation of free oxygen radicals. Most investigators in this field have used the spin-trap 5,5'-dimethyl-N-pyrroline-N-oxide (DMPO) to stabilize these short-lived radicals and make them visible by means of the electron spin resonance (ESR) technique. ESR signals obtained from intravascular DMPO were reported to indicate the formation of free OH. radicals and, in some cases, also carbon-centered radicals. We were unable to confirm these findings. Carbon-centered radicals were not obtained irrespectively of conditions studied, while oxygen-centered DMPO-adducts could only be detected in minor amounts. Instead, we observed an ascorbyl-related ESR signal. The addition of ethylenediaminetetraacetic acid (EDTA), which was used by many investigators in this field, was found to greatly influence ESR-spectra of the reperfusion fluid. The ascorbyl radical concentration was clearly reduced and the DMPO-OH. adduct became more prominent. The addition of iron further stimulated this change eliciting a Fenton-type reaction responsible for DMPO-OH.-related ESR spectra in the perfusate after ischemia. Accordingly, we observed the release of iron and ascorbic acid into the perfusate as a consequence of ischemia. We could demonstrate that iron in the presence of ascorbate and EDTA causes both types of radicals detected in the perfusate. DMPO-OH. generation in the presence of EDTA was found to result from free OH. radicals that were not generated in the absence of EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is oxidative stress primarily involved in reperfusion injury of the ischemic heart? 166 1

Complex of vitamins E and C showed the most effective antinecrotic action in rats with simulated myocardial infarction in series of antioxidants studied: ascorbate, alpha-tocopherol, quercetine, derivatives of o-benzoquinone OBQ2 and OBQ3. Stabilization of lipid peroxidation in cardiomyocytes, increase in biomembranes stability and absence of distinct alterations in the antioxidative enzymatic system were found in rats with ischemia and myocardial infarction after treatment with the complex. Protective effect of the vitamins E and C complex was realised via antiradical mechanism.
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PMID:[Efficacy of various antioxidants in experimental ischemia and myocardial infarct in the rat]. 175 Feb 12


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