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

We have previously reported that the combined administration of mannitol and perfluorochemical blood substitutes is evidently effective in protecting the brain from cerebral ischemia. This experimental study was designed to develop more effective method in suppressing brain infarction than the combined treatment of mannitol and PFC. Using the "Canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump, the effect of eight agents including six kinds as the free radical scavenger on cerebral ischemia was investigated. Eight agents were mannitol, vitamin E (Vit. E), dimethyl sulfoxide (DMSO), vitamin C, glycerol, nizofenone (Y-9179), dexamethasone (Dexa.) and suloctidil (MY-103). After pretreatment with each agent, blood flow was reduced via the pump to 1/10 of the normal state and 1 hour later, return to the normal state was allowed. Subsequent changes in EEG were observed and the effects of the drugs evaluated. In the control group, no recovery of electrical activity was seen, but in six groups among eight treated groups, i.e., treated with mannitol, Vit. E, DMSO, MY-103, Y-9179 and Dexa, gradual emergence of slow waves was observed. And more favorable effects were found when the combined administration of mannitol, Vit. E and Dexa was made in the same experimental schedule as compared with the single administration of each of these drugs. Furthermore in the animals administered with PFC in combination with mannitol, Vit. E and Dexa, flattening of electrical activity could not be seen throughout the period of severe ischemia. Moreover, the power of electrical activity recovered nearly to the preischemic state immediately after recirculation. Although the possible mechanisms are not yet completely clarified, the present results are thought to indicate that this new combination therapy utilizing PFC with mannitol, Vit. E and Dexa may be useful in the treatment of cerebral ischemia.
 ...
PMID:[Experimental study of cerebral protective effect on cerebral ischemia of various antioxidants and other agents. With special reference to the combined treatment of mannitol, vitamin E, dexamethasone and perfluorochemicals]. 632 77

The ascorbic acid/dehydroascorbic acid system was analyzed in the cerebrospinal fluid (CSF) of 41 patients with different neurological disorders. The chi-square test of covariance analysis revealed in this sample significant differences in the CSF levels of total ascorbic acid when patients were classified by diagnostic categories. The population analyzed contained a group of 18 patients (back pain/sciatica group) in whom no overt neurological abnormalities were disclosed upon evaluation. Taking the CSF levels of total ascorbic acid and dehydroascorbic acid in these patients as the reference (3.57 +/- 0.87 (SD)/100 ml and 0.53 +/- 0.19 mg/100 ml, respectively), it was found that head-traumatized patients showed a significant reduction in the concentration of total ascorbic acid in the CSF. CSF ascorbic acid levels were also significantly lower in patients with increased intracranial pressure (noninfected hydrocephalus group) and in patients with cerebral tumors. Although the CSF concentration of dehydroascorbic acid did not correspondingly increase over the reference values in these three groups of patients, the tendency existed for dehydroascorbic acid to represent in them a higher percentage of total ascorbic acid. After examining different alternatives, it is concluded that the hypothesis of free radical damage to the central nervous system after certain types of injury (trauma, ischemia, and tumors) may provide a satisfactory explanation of our findings. A rationale for the use of vitamin C in the management of some neurological patients is also derived from this work.
 ...
PMID:Cerebrospinal fluid ascorbic acid levels in neurological disorders. 670 36

If 60 min long ischemia of a liver tissue lobe occurred after feeding of rats with oil emulsion of alpha-tocopherol at a dose of 50 mg/kg within 12 hrs during 2 days, the "ischemic" decrease in metabolism of amidopyrine and aniline, in content of cytochrome P-450 and activity of initial and middle steps of NADPH-dependent redox chain as well as intensification of ascorbate-dependent peroxidation of membrane lipids were prevented in endoplasmic reticulum of hepatocytes. The protective effect of alpha-tocopherol on these xenobiotics metabolism is apparently related to an increase in catalytic activity of cytochrome P-450, to the enzyme antioxidant and membrane-stabilizing properties.
 ...
PMID:[Effect of alpha-tocopherol on the hydroxylating system and lipid peroxidation in membranes of endoplasmic reticulum from ischemic rat liver]. 683 66

Thirty minutes of total cerebral ischemia (decapitation) decreased total glutathione (GSH + GSSG) by 7% but had no detectable effect on the concentration of oxidized glutathione (GSSG), reduced ascorbate, or total ascorbate, In a model of reversible, bilateral hemispheric ischemia (four-vessel occlusion) no changes in glutathione or ascorbate were detected after 30 min of ischemia. During 24 h of reperfusion following such an insult no detectable change in total ascorbate, reduced ascorbate, or oxidized glutathione was noted: however, total brain glutathione declined by 25%. The findings are discussed in relation to the hypothesis that the deleterious effects of ischemia are due to an increase in free radical production which in turn leads to increased lipid peroxidation.
 ...
PMID:Glutathione and ascorbate during ischemia and postischemic reperfusion in rat brain. 745 15

In this study, we examined the effects of oxidative stress adaptation on myocardial ischemic reperfusion injury. Oxidative stress was induced by injecting endotoxin (0.5 mg/kg) into the rat. After 24 h, rats were killed, hearts were isolated, and the effects of ischemia-reperfusion were studied using an isolated working heart preparation. The development of oxidative stress was examined by assessing malonaldehyde production in the heart. The antioxidant defense system was studied by estimating antioxidant enzyme activities and ascorbate- as well as thiol-dependent antioxidant reserve. The results of our study indicated that endotoxin induced oxidative stress within 1 h of treatment; the stress was reduced progressively and steadily up to 24 h. The antioxidant enzymes superoxide dismutase, catalase, glutathione (GSH) peroxidase, and GSH reductase were lowered up to 2 h and then increased. Both thiol- and ascorbate-dependent antioxidant reserve were enhanced, but the enhancement of the former was only transitory. After 24 h, endotoxin provided adequate protection to the heart from the ischemic-reperfusion injury, as evidenced by improved left ventricular function and aortic flow. Our results suggest that the induction of oxidative stress by endotoxin-induced adaptive modification of the antioxidant defense in the heart, thereby reducing ischemic-reperfusion injury.
 ...
PMID:Myocardial adaptation to ischemia by oxidative stress induced by endotoxin. 748 60

A large number of experimental studies suggests that oxygen free radicals play a major role in the pathogenesis of the myocardial lesions observed during the sequence ischemia-reperfusion. The purpose of this study was to determine whether oxygen free radicals can induce thrombosis. In so doing we have developed a new experimental thrombosis model. Reproducible focal thrombosis has been achieved by irradiating mesenteric arterioles of rat for variable time with green filtered light issuing from a mercury lamp after systemic injection of different rose bengal doses. The number of emboli that remove in the blood (N), the duration of total occlusion (T) and the number of emboli per minute were then measured. As control, no rose bengal administration was done and the vessels were exposed to the filtered light. In comparison with this control, results clearly showed that free radicals always induced thrombosis and the induced thrombus was mainly composed of platelets. In this new thrombosis model induced by free radicals antithrombotic drugs (aspirin, 200 mg/Kg, heparin, 2 mg/Kg) and antioxidants (vitamin C, 10 and 20 mg/Kg, allopurinol, 200 and 300 mg/Kg, vitamin E, 500 and 1000 mg/Kg) have been tested. Results have shown that only heparin and vitamin E had an antithrombotic effect on thrombus formation induced by free radicals. This model should be useful in studying the effects of different drugs and could lead to new treatment modalities for ischemic accident and other cardiovascular diseases.
 ...
PMID:Experimental thrombosis model induced by free radicals. Application to aspirin and other different substances. 749 98

There is controversy concerning the ability of antioxidant vitamins to reduce myocardial infarct size. We sought to determine whether a brief prophylactic treatment of vitamin C or vitamin C plus Trolox (a water-soluble form of vitamin E) could reduce myocardial infarct size in an experimental model. We used an anesthetized open-chest rabbit model in which a branch of the circumflex coronary artery was ligated for 30 minutes followed by 4 hours of reperfusion. Experiments were performed in a randomized and blinded fashion. An IV injection of normal saline pH balanced to 7.4 (control group n = 15), vitamin C (150 mg/kg, n = 14), or vitamin C plus Trolox (150 mg/kg plus 100 mg/kg, respectively, n = 15) was administered prior to coronary occlusion. Collateral blood flow during coronary occlusion was measured by radioactive microspheres, myocardial risk zone (AR) was assessed by blue dye injection, and myocardial infarct size (AN) was assessed by triphenyltetrazolium chloride staining. All rabbits received comparable ischemic insult: Collateral blood flow and AR were similar among all three groups. Infarct size, measured as a percent of AR, did not differ significantly among the controls (21%), vitamin C (29%), or the vitamin C plus Trolox (18%) groups. Therefore, in this ischemia/reperfusion model, antioxidant vitamins did not alter myocardial infarct size.
 ...
PMID:Do antioxidant vitamins reduce infarct size following acute myocardial ischemia/reperfusion? 754 Apr 23

The antioxidant properties of nitecapone, a catechol derivative and an inhibitor of catechol-O-methyltransferase, were reported recently. In the present study, the influence of nitecapone on isolated rat heart ischemia-reperfusion injury was investigated to elucidate its cardioprotective role. Nitecapone, administered in the perfusion buffer from the beginning of the pre-ischemic phase, significantly improved recovery of cardiac mechanical function, suppressed enzyme leakage in the coronary effluent, and minimized loss of ascorbate, compared with the control group. In rats fed a diet containing 4% ascorbate, myocardial ascorbate content in ascorbate-fed rats after ischemia-reperfusion was higher than that in control rats fed a normal diet without ischemia. However, supplemented rats did not show any beneficial effects on cardiac mechanical recovery or enzyme leakage, suggesting that maintenance of tissue ascorbate level is not the cause, but the result of the protective effects of nitecapone against cardiac ischemia-reperfusion injury. The iron-chelating effect of nitecapone was also tested. It was confirmed, using electron spin resonance, that 50 microM nitecapone chelates the same concentration of iron released from the heart into the coronary effluent. Hence, the iron-chelating ability of nitecapone may be responsible, at least in part, for its cardioprotective effects in ischemia-reperfusion injury.
 ...
PMID:Role of ascorbate in protection by nitecapone against cardiac ischemia-reperfusion injury. 757 46

Ascorbate and glutathione (GSH) are the primary water-soluble antioxidants in the CNS. Oxidative stress, sometimes indicated by loss of these antioxidants, has been linked to several clinical and experimental conditions, including cerebral ischemia. These conditions are also gender-linked, with greater incidence or severity in males than females. To test whether there are gender differences in oxidant/antioxidant regulation, we determined basal levels of ascorbate and GSH in rat brain and their loss after 1 h decapitation ischemia. We found that ascorbate levels in male rat brain were 7-10% higher than in females, depending on region, whereas GSH levels were gender-independent. Significant ascorbate loss (up to 12%) occurred in males during ischemia, with a regional pattern of cerebellum > hippocampus > prefrontal cortex. Loss of ascorbate in females was not significant in any region. By contrast, loss of GSH was significant in both males and females. Greater loss of GSH than ascorbate was in agreement with previous studies and was consistent with loss from enzymatic degradation, as well as oxidation. The significant gender difference in ascorbate loss, as a marker of oxidative stress, supports the hypothesis that inherent differences in oxidant/antioxidant regulation contribute to gender differences in response to ischemia and other pathological conditions.
 ...
PMID:Gender differences in cerebral ascorbate levels and ascorbate loss in ischemia. 757 30

A growing body of experimental data indicate that oxygen radicals may mediate the brain injury during ischemia-reperfusion. One potential source of oxygen radicals is activated neutrophils. To study the role of neutrophils in radical production during cerebral ischemia-reperfusion, we evaluated the effects of depletion of circulating neutrophils by administration of an anti-neutrophil monoclonal antibody (RP3) on radical formation in rats with 1-h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents. In the vehicle controls, extracellular AR decreased during MCA occlusion. After reperfusion, AR significantly increased at 30 min and 1 h, returned to near basal level until 2 h, and increased again at 24 h after reperfusion. In the rats treated with RP3, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, RP3 treatment completely inhibited the increase in extracellular AR after reperfusion. RP3 treatment exerted no effect on the changes in extracellular ascorbate or tissue PO2 throughout the experimental period. In conclusion, neutrophils are a major source of oxygen radicals during reperfusion after focal cerebral ischemia.
 ...
PMID:Role of neutrophils in radical production during ischemia and reperfusion of the rat brain: effect of neutrophil depletion on extracellular ascorbyl radical formation. 759 54


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