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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the association of PON1 55/192 polymorphisms with type, severity and prognosis of stroke and oxidative markers. Paraoxonase1 (PON1), Glutathione Reductase (GSH-Rd) and Malondialdehyde (MDA) levels were measured at day 1 and at day 5 following the onset of stroke. Genotypes were determined by polymerase chain reaction and restriction digestion. The frequencies of QQ and MM genotypes of PON1 192 and PON1 55, respectively, were significantly higher in controls than in patients. However, the allele frequencies of PON1 192 R and PON1 55 L were significantly more frequent in patients compared to controls. The frequency of combined genotype of RR/LL was significantly higher in cardioembolic group than in atherothrombotic group. PON1 activities were significantly diminished in stroke patients compared to controls. In contrast, serum MDA levels were significantly greater in patients than the values in controls. GSH-Rd activity was higher in patients with small lesion and good prognosis than those with large and poor prognosis. Low density lipoprotein (LDL) levels in patients with large lesions were higher than those with small lesions. PON1 55/192 polymorphisms influence activity of the enzyme. PON1 55/192 genotypes have been associated with MDA levels. In conclusion, PON1 genetic variations are associated with risk factors, severity, type and prognosis of stroke and oxidative stress.
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PMID:PON1 55/192 polymorphism, oxidative stress, type, prognosis and severity of stroke. 1676 84

Reduced supply of glucose involves in many pathological conditions such as stroke and contributes to ischemic injuries. In contrast, hyperglycemia has also been regarded as an important factor in causing and exaggerating stroke damage. Although the molecular mechanism(s) of imbalanced glucose-induced cellular injuries under low oxygen conditions are not clear, oxidative stress has been implicated in both hypo- and hypeglycemic damage. Redox status is critical for the regulation of cellular signaling and cell survival. The effects of glucose levels on redox status are not well understood in neurons under hypoxia. The purpose of this study was to determine the effects of glucose concentration on the redox status of rat primary neurons under hypoxia. The cellular redox status was determined from GSH/GSSG ratios, and oxidation of 2,3-dichlorofluorscein diacetate was used to assess levels of reactive oxygen species (ROS). We found that glucose levels were critical in regulating redox state in these neurons under hypoxia. The results showed that under hypoxic conditions: (1) there was an optimal glucose concentration (25mM) at which neurons maintained a reducing environment and showed the lowest levels of ROS and cell death; (2) in the concentration range of 0-25mM, the presence of glucose increased cellular GSH/GSSG ratio and reduced ROS and cell death; and (3) over-supply of glucose (25-100mM) elevated ROS levels, produced an oxidizing environment, and increased cell death. These results suggest that cellular redox status regulated by glucose may play an important role in glucose-mediated cellular responses in hypoxia.
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PMID:Effects of glucose concentration on redox status in rat primary cortical neurons under hypoxia. 1705 60

Oxidative stress is implicated in the pathogenesis of ischemia/reperfusion injury. Recently, we demonstrated that activation of CD36, a class B scavenger receptor, mediates free radical production and tissue injury in cerebral ischemia (1). Oxidized low density lipoproteins (oxLDL) are among the ligands that bind to CD36 and are elevated in acute cerebral infarction. SS31 is a cell-permeable antioxidant peptide that reduces intracellular free radicals and inhibits LDL oxidation/lipid peroxidation (2). The current study was designed to investigate whether treatment with SS31 normalizes ischemia-induced redox changes and attenuates CD36-mediated tissue injury. C57BL/6 mice were subjected to transient middle cerebral artery occlusion (MCAO). Redox status and infarct volume were measured in animals treated with either saline or SS31. Oxidative stress induced by ischemia/reperfusion profoundly depleted glutathione (GSH) concentrations in the ipsilateral cortex and striatum. Treating mice with SS31 immediately after reperfusion significantly attenuated ischemia-induced GSH depletion in the cortex and reduced infarct size. By contrast, the protective effect of SS31 was absent in CD36 knock-out mice, indicating that SS31 is acting through inhibition of CD36. Treating C57BL/6 mice with SS31 reduced CD36 expression in postischemic brain and mouse peritoneal macrophages (MPM). Further in vitro studies revealed that SS31 attenuated oxLDL-induced CD36 expression and foam cell formation in MPM. These in vivo and in vitro studies indicate that the down-regulation of CD36 by novel class antioxidant peptides may be a useful strategy to treat ischemic stroke victims.
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PMID:A novel cell-permeable antioxidant peptide, SS31, attenuates ischemic brain injury by down-regulating CD36. 1717 11

A dynamic assessment of oxygen status of the arterial blood, activity of antioxidant system enzymes (AOS), succinatedehydrogenase (SDG), mitochondrial alpha-glycero-phosphate-dehydrogenase (alpha-GPDH) and alkaline phosphatase (AP) as well as concentrations of reduced glutathione (GSH) and secondary products of lipid peroxidation reacting with thiobarbituric acid (PLPRTA) has been carried out in patients at the acute stage of ischemic stroke of hemispheric location. Relative hyperoxia as a result of the hyperventilation syndrome was mostly pronounced on day 1 and 3. At the same time, a reduced activity of AOS system and an increase of PLPRTA concentration have been observed from the 1st day after stroke. There were also a decrease of the SDG activity and a marked (2,8 fold) increase of the alpha-GPDH activity as compared to the controls. A decrease of the AP leukocyte activity in the peripheral blood to day 7 after stroke makes possible a prognosis of good functional rehabilitation to the 21st day of the disease. Therefore, the results of the study suggest that the development of oxidative stress in patients with ischemic stroke is caused by tprimary disruption of bioenergetic processes during the reduction of AOS activity.
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PMID:[Oxidative stress and oxygen status in ischemic stroke]. 1731 Jul 94

The release of zinc (Zn) from glutamatergic synapses contributes to the neuropathology of ischemia, traumatic brain injury, and stroke. Astrocytes surround glutamatergic synapses and are vulnerable to the toxicity of Zn, which impairs their antioxidative glutathione (GSH) system and elevates the production of reactive oxygen species (ROS). It is not known whether one or both of these actions are the primary cause of Zn-induced cell death in astrocytes. Using primary rat astrocyte cultures we have examined whether Zn-mediated impairment of GSH redox cycling is the main source of its toxicity. Zn acetate at concentrations of 100 microM or greater were found to inactivate glutathione reductase (GR) via an NADPH-dependent mechanism, while concentrations of 150 microM and above caused substantial cell death. Furthermore, Zn increased the ratio of GSSG:GSH in astrocytes, increased their export of GSSG, slowed their clearance of exogenous H2O2, and promoted the intracellular production of ROS. In contrast, the GR inhibitor, carmustine, did not induce cell death, cause the production of ROS, or alter the GSH thiol redox balance. Taken together these results indicate that Zn toxicity in astrocytes is primarily associated with the generation of intracellular ROS, rather than the inhibition of GR.
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PMID:Zinc stimulates the production of toxic reactive oxygen species (ROS) and inhibits glutathione reductase in astrocytes. 1738 3

Mercury, cadmium, and other heavy metals have a high affinity for sulfhydryl (-SH) groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (NAC, ALA, GSH), with subsequent decreased oxidant defense and increased oxidative stress. Both bind to metallothionein and substitute for zinc, copper, and other trace metals reducing the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction with reduction in ATP, depletion of glutathione, and increased lipid peroxidation; increased oxidative stress is common. Selenium antagonizes mercury toxicity. The overall vascular effects of mercury include oxidative stress, inflammation, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, immune dysfunction, and mitochondrial dysfunction. The clinical consequences of mercury toxicity include hypertension, CHD, MI, increased carotid IMT and obstruction, CVA, generalized atherosclerosis, and renal dysfunction with proteinuria. Pathological, biochemical, and functional medicine correlations are significant and logical. Mercury diminishes the protective effect of fish and omega-3 fatty acids. Mercury, cadmium, and other heavy metals inactivate COMT, which increases serum and urinary epinephrine, norepinephrine, and dopamine. This effect will increase blood pressure and may be a clinical clue to heavy metal toxicity. Cadmium concentrates in the kidney, particularly inducing proteinuria and renal dysfunction; it is associated with hypertension, but less so with CHD. Renal cadmium reduces CYP4A11 and PPARs, which may be related to hypertension, sodium retention, glucose intolerance, dyslipidemia, and zinc deficiency. Dietary calcium may mitigate some of the toxicity of cadmium. Heavy metal toxicity, especially mercury and cadmium, should be evaluated in any patient with hypertension, CHD, or other vascular disease. Specific testing for acute and chronic toxicity and total body burden using hair, toenail, urine, serum, etc. with baseline and provoked evaluation should be done.
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PMID:The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. 1740 90

The effect of chloroform: methanolic (80:20) extract of C. asiatica (CA; 100 and 200 mg/kg), was evaluated on the course of free radical generation and excitotoxicity in monosodiumglutamate (MSG) treated female Sprague Dawley rats. The extract showed significant improvement in catalase, super oxide desmutase and lipid peroxides levels in hippocampus and striatum regions. Glutathione level was not altered with CA treatment. Similar observation was made with dextromethorphan. The general behavior, locomotor activity and CAl a region of the hippocampus was significantly protected by CA indicating neuroprotective effect of CA in MSG induced excitotoxic condition. Hence it can be concluded that CA protected MSG induced neurodegeneration attributed to its antioxidant and behavioural properties. This activity of CA can be explored in epilepsy, stroke and other degenerative conditions in which the role of glutamate is known to play vital role in the pathogenesis.
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PMID:Neuroprotective evaluation of standardized extract of Centella asciatica in monosodium glutamate treated rats. 1756 83

The present study was carried out to investigate the effect of the combination of an endothelin antagonist TAK-044 and an antiinflammatory agent aspirin in middle cerebral artery (MCA) occlusion model of acute ischemic stroke in rats. Male Wistar rats were pretreated with TAK-044 (5 mg/kg, i.p.) and aspirin (50 mg/kg, i.p.) for 7 days individually and in combination in different groups, and were thereafter subjected to focal ischemia for 2 h by occlusion of MCA using intraluminal thread. Twenty-four hours later, the rats were subjected to motor performance tests and killed subsequently for estimation of markers of oxidative stress malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD). The control group received the vehicle and the same protocol was followed. In vehicle-treated MCA occluded rats, significant (p < 0.01) motor impairment, with elevated levels of MDA (600.8 +/- 14.4 nmol/g tissue) and decreased levels of GSH (61.1 +/- 3.1 microg/g tissue) and SOD (8.5 +/- 0.5 U/mg protein,) was observed. Pretreatment with TAK-044 and aspirin for 7 days significantly improved motor function and attenuated the raised levels of MDA (475 +/- 14 and 538 +/- 17.3 nmol/g tissue, respectively) and the decrease in GSH (101 +/- 5 and 100 +/- 4.5 microg/g tissue, respectively) and SOD (12.1 +/- 0.5 and 10.5 +/- 0.6 U/mg protein, respectively), as compared to vehicle-treated MCA occluded rats. Combination of both the agents did not show a significant difference as compared to the individual drugs alone. The present study demonstrates that, although protection was observed with both the drugs (TAK-044 and aspirin), there was no enhanced effect when both agents were given in combination.
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PMID:Effect of combination of endothelin receptor antagonist (TAK-044) and aspirin in middle cerebral artery occlusion model of acute ischemic stroke in rats. 1760 37

The generation of free radicals is a cause of many pathological conditions like diabetes mellitus, cancer, stroke, etc. Free radicals cause damage to cellular DNA and initiate carcinogenesis. Free radicals also bring about proliferation of cells via cell signaling. An inverse relationship between the consumption of vegetable diets and the risk of cancer has been established. In the present study, Star anise (Illicium verum), which is a commonly used condiment in Indian cuisine, was assessed for its anti-carcinogenic potential in N-nitrosodiethylamine (NDEA) initiated and phenobarbital (PB) promoted hepato-carcinogenesis. Rats were randomly selected for eight experimental groups. The carcinogenesis was induced by injecting the rats, with a single dose of NDEA (200mg/kg body weight) intraperitoneally as initiator, followed by promotion with PB (0.05%) in drinking water for 14 consecutive weeks. The treatment with NDEA increased liver weight, while Star anise (Star) treatment reduced the liver weight of rats. The treatment with Star throughout for 20 weeks or during the promotion stage (6-20 weeks) significantly reduced the nodule incidence and nodule multiplicity in the rats, while the treatment with Star at the initiation phase (first 4 weeks) only could not reduce these parameters. The treatment with Star for 20 consecutive weeks significantly reduced the nodule size and nodule volume. The treatment with Star throughout as well as at the promotion stage lowered the lipid peroxidation (LPO) in liver and erythrocytes, while the LPO was not lowered, when Star was administered during initiation stage only. The treatment with Star restored the liver and erythrocyte super-oxide dismutase (SOD) activities to normal in the carcinogenesis-induced rats. The liver catalase (CAT) activity increased in all the treated groups. The erythrocyte CAT activity increased in the rats treated with Star during initiation and promotion stage only. The liver glutathione (GSH) level increased significantly in the groups treated with Star. The erythrocyte GSH level was lowered in the rats treated with NDEA and PB, however, Star treatment helped in increasing the erythrocyte GSH level to some extent. The liver and erythrocyte glutathione-S-transferase (GST) activity increased in all the groups treated with NDEA and PB. The treatment with Star decreased GST level significantly. These results indicate that the treatment with Star reduces the tumor burden, lowers oxidative stress and increases the level of phase II enzymes, which may contribute to its anti-carcinogenic potential.
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PMID:Chemo-preventive effect of Star anise in N-nitrosodiethylamine initiated and phenobarbital promoted hepato-carcinogenesis. 1765 3

Glutamate, a major excitatory neurotransmitter in the CNS, plays a critical role in neurological disorders such as stroke and Parkinson's disease. Recent studies have suggested that glutamate excess can result in a form of cell death called glutamate-induced oxytosis. In this study, we explore the protective effects of necrostatin-1 (Nec-1), an inhibitor of necroptosis, on glutamate-induced oxytosis. We show that Nec-1 inhibits glutamate-induced oxytosis in HT-22 cells through a mechanism that involves an increase in cellular glutathione (GSH) levels as well as a reduction in reactive oxygen species production. However, Nec-1 had no protective effect on free radical-induced cell death caused by hydrogen peroxide or menadione, which suggests that Nec-1 has no antioxidant effects. Interestingly, the protective effect of Nec-1 was still observed when cellular GSH was depleted by buthionine sulfoximine, a specific and irreversible inhibitor of glutamylcysteine synthetase. Our study further demonstrates that Nec-1 significantly blocks the nuclear translocation of apoptosis-inducing factor (a marker of caspase-independent programmed cell death) and inhibits the integration of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (a pro-death member of the Bcl-2 family) into the mitochondrial membrane. Taken together, these results demonstrate for the first time that Nec-1 prevents glutamate-induced oxytosis in HT-22 cells through GSH related as well as apoptosis-inducing factor and Bcl-2/adenovirus E1B 19 kDa-interacting protein 3-related pathways.
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PMID:Necrostatin-1 protects against glutamate-induced glutathione depletion and caspase-independent cell death in HT-22 cells. 1776 Aug 69


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