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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species (ROS) can play an important role in the pathogenesis of ischemia-reperfusion (I/R) injury. Dehydroepiandrosterone (DHEA) is one of the hormones secreted from adrenal glands, and in some studies it has been shown that DHEA has antioxidant properties. This experimental study was designed to determine the effect of DHEA on I/R-induced oxidative stress in rabbit kidney. Twenty-one rabbits were divided into three groups. Rabbits were subjected to 60 min of left renal pedicle occlusion followed by 24 h of reperfusion. DHEA (50 mg/kg) (I/R + DHEA group) or equal volume of vehicle (I/R group) was administered 3 h prior to ischemia. The control group received only laparotomy without I/R, DHEA or vehicle. At the end of the reperfusion periods, rabbits were decapitated. Renal tissues were taken for determination of malondialdehyde (MDA) levels as an indicator of lipid peroxidation and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities as antioxidant enzymes. In the I/R group, while renal SOD and CAT activities were significantly lower, MDA levels were significantly higher than in the I/R + DHEA group and controls. In the I/R + DHEA group, enzyme activities and MDA levels were similar to the controls. There was no significant difference in terms of renal GPX activity among the groups. DHEA may have a beneficial effect on renal tissue against oxidative damage due to I/R by preventing decreases in some antioxidant enzyme activities.
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PMID:The effect of dehydroepiandrosterone on renal ischemia-reperfusion-induced oxidative stress in rabbits. 1525 Jan 1

The effects of neurosteroids, 17beta-estradiol and dehydroepiandrosterone-sulfate (DHEA-S), were investigated on retinal degeneration using a rat model of ischemia-reperfusion injury. The animals were anaesthetized and retinal ischemia was induced by elevating the intraocular pressure to 120 mm Hg for 45 min. Neurosteroids were injected intraperitoneally before ischemia and immediately after reperfusion. Retinal biochemical changes such as increase of lactate content and decrease of glucose and ATP were significantly inhibited by neurosteroids compared to the control ischemic group. The effects of 17beta-estradiol and DHEA-S were antagonized by pre-treatment with the sigma1 site antagonist. These findings suggest that 17beta-estradiol and dehydroepiandrosterone-sulfate may affect the metabolic state of surviving neurons and glial cells after ischemic injury and that they act, at least in part, through involvement of sigma1 recognition sites.
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PMID:Effects of neurosteroids on ischemia-reperfusion injury in the rat retina: role of sigma1 recognition sites. 1536 83

There is evidence that the excessive generation of reactive oxygen free radicals contributes to the brain injury associated with cerebral ischemia. In the present study, the protective effect of chronic administration of ethyl docosahexaenoate (E-DHA) against oxidative brain injury was evaluated in the gerbil model of transient cerebral ischemia. Weanling male gerbils were orally pretreated with either E-DHA (200 mg/kg) or vehicle, once a day, for 10 weeks and subjected to bilateral occlusion of common carotid arteries for 10 min. At the different reperfusion times, E-DHA pretreatment significantly inhibited the increases in the production of brain salicylate-derived 2,5-dihydroxybenzoic acid (2,5-DHBA) and content of brain malonildialdehyde (MDA). The superoxide dismutase (SOD) activity was not modified; however, pretreatment with E-DHA significantly prevented the level of brain-reduced glutathione (GSH) and activities of brain glutathione peroxidase (GSH-P(X)) and catalase (CAT) from declines caused by cerebral ischemia. Moreover, ischemia and reperfusion-induced delayed neuronal loss in the hippocampus CA1 sector and locomotor hyperactivity were also significantly attenuated by pretreatment with E-DHA. These results suggested that the neuroprotective effect of E-DHA might be due to its antioxidant property.
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PMID:Protective effect of chronic ethyl docosahexaenoate administration on brain injury in ischemic gerbils. 1558 73

Many functions have been attributed to neurosteroids including actions as anxiolytics, roles in myelination, inhibitors of neuronal toxicity and ischemia, and roles in neuronal growth and differentiation. To understand the functions of neurosteroids during nervous system development, we used two mouse models: one, in which the cyp17 gene was ablated, thus ablating synthesis of the neurosteroid DHEA, and a second, in a mouse model of a human childhood fatal neurodegenerative disease, Niemann-Pick Type C (NP-C). Cyp17-/- mice died unexpectedly approximately embryonic day 7. Cyp17 was expressed in the embryonic endoderm at E7, where 17alpha hydroxylase and c17,20 lyase activities were found. Hormonal replacement was ineffective in rescuing the embryos. The function of P450c17 and/or its steroid products in early mouse development is unknown. In the second model, we used a naturally-occurring NP-C mutant mouse. Mutations in the npc1 gene results in lysosomal accumulation of cholesterol and gangliosides in humans and in the mouse, which also recapitulates the onset of neurological deficits, neuronal loss and death typical of the most severe form of the human disease. We showed that there is a substantial reduction in the synthesis of the neurosteroid allopregnanolone (ALLO) at birth, which may lead to abnormal neural development. ALLO treatment was highly effective; ALLO-treated NP-C mice had substantially increased survival and delays in neurologic impairments, coinciding with marked improvements in neuronal survival, and reduction of gangliosides. These data suggest that neurosteroids play an important role in brain development and maturation and may be an effective therapy for NP-C and perhaps other lysosomal storage diseases.
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PMID:Niemann pick type C disease as a model for defects in neurosteroidogenesis. 1566 18

Arachidonic acid (AA) and its vasoactive metabolites have been implicated in the pathogenesis of brain damage induced by cerebral ischemia. The membrane AA concentrations can be reduced by changes in dietary fatty acid intake. The purpose of the present study was to investigate the effects of chronic ethyl docosahexaenoate (E-DHA) administration on the generation of eicosanoids of AA metabolism during the period of reperfusion after ischemia in gerbils. Weanling male gerbils were orally pretreated with either E-DHA (100, 200 mg/kg) or vehicle, once a day, for 10 weeks, and subjected to transient forebrain ischemia by bilateral common carotid occlusion for 10 min. E-DHA (200 mg/kg) pretreatment significantly decreased the content of brain lipid AA at the termination of treatment, prevented postischemic impaired regional cerebral blood flow (rCBF) and reduced the levels of brain prostaglandin (PG) PGF(2alpha) and 6-keto-PGF(1alpha), and thromboxane B(2) (TXB(2)), as well as leukotriene (LT) LTB(4) and LTC(4) at 30 and 60 min of reperfusion compared with the vehicle, which was well associated with the attenuated cerebral edema in the E-DHA-treated brain after 48 h of reperfusion. These data suggest that the E-DHA (200 mg/kg) pretreatment reduces the postischemic eicosanoid productions, which may be due to its reduction of the brain lipid AA content.
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PMID:Chronic administration of ethyl docosahexaenoate reduces gerbil brain eicosanoid productions following ischemia and reperfusion. 1609 34

Pathological conditions in the brain, such as ischemia, trauma and seizure are accompanied by increased levels of free n-6 and n-3 polyunsaturated fatty acids (PUFA), mainly arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3). A neuroprotective role has been suggested for PUFA. For investigation of the potential molecular mechanisms involved in neuroprotection by PUFA, we studied the regulation of the concentration of intracellular Ca2+ ([Ca2+]i) in rat brain astrocytes. We evaluated the presence of extracellular PUFA and the release of intracellular PUFA. Interestingly, only the constitutive brain PUFA AA and DHA, but not eicosapentaenoic acid (EPA) had prominent effects on intracellular Ca2+. AA and DHA suppressed [Ca2+]i oscillation, inhibited store-operated Ca2+ entry, and reduced the amplitudes of Ca2+ responses evoked by agonists of G protein-coupled receptors. Moreover, prolonged exposure of astrocytes to AA and DHA brought the cells to a new steady state of a moderately elevated [Ca2+]i level, where the cells became virtually insensitive to external stimuli. This new steady state can be considered as a mechanism of self-protection. It isolates disturbed parts of the brain, because AA and DHA reduce pathological overstimulation in the tissue surrounding the damaged area. In inflammation-related events, frequently AA and DHA exhibit opposite effects. However, in astrocytes AA and DHA exerted comparable effects on [Ca2+]i. Extracellularly added AA and DHA, but not EPA, were also able to induce the release of [3H]AA from prelabeled astrocytes. Therefore, we also suggest the involvement of phospholipase A2 activation and lysophospholipid generation in the regulation of intracellular Ca2+ in astrocytes.
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PMID:Regulation of intracellular calcium levels by polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid, in astrocytes: possible involvement of phospholipase A2. 1618 12

Recently, we reported that dietary ethyl docosahexaenoate (Et-DHA) intake decreases the level of membrane arachidonic acid (AA), which reduces the generation of AA metabolites in ischemic gerbil brain. As an extended study, we further investigated the influence of the chronic administration of Et-DHA on free AA levels after ischemia. In addition, Na,K-ATPase activity, cation content, cerebral edema and brain damage were also evaluated. Weanling male gerbils were orally pretreated with either Et-DHA (200 mg/kg) or vehicle, once a day for 10 weeks, and subjected to transient forebrain ischemia by bilateral common carotid occlusion for 30 min. Time-course analyses revealed that pretreatment with Et-DHA, compared with pretreatment with the vehicle, significantly decreased the brain's free AA levels during ischemia (5, 15 and 30 min) and after reperfusion (5, 10, 15 and 30 min), and attenuated the decline of Na,K-ATPase activity at examined time points. Pretreatment with Et-DHA significantly prevented an increase in Na(+) concentration and a decrease in K(+) concentration after 24 h of reperfusion, which resulted in lower cerebral water content. Reduced brain infarct volume and low animal mortality were also observed in Et-DHA-treated animals. These data suggest that the reduction of ischemia-induced AA liberation and accumulation by Et-DHA pretreatment may be attributable to (a) protection against the decline of Na,K-ATPase activity, (b) postischemic cerebral edema and brain damage and (c) animal mortality.
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PMID:Chronic daily administration of ethyl docosahexaenoate protects against gerbil brain ischemic damage through reduction of arachidonic acid liberation and accumulation. 1686 Sep 80

Polyunsaturated fatty acids (PUFAs) such as docosahexaenoic and eicosapentaenoic acids (DHA, EPA) exert ischemic anti-arrhythmic effects. However, their mechanism of action remains unknown. The present study was designed to investigate their potential effect on the regulation of the late sodium current as the basis for their ischemic anti-arrhythmic activity. Human isoforms of wild-type SCN5A and DeltaKPQ-mutated cardiac sodium channels were stably transfected in HEK 293 cells and, the resulting currents were recorded using the patch clamp technique in whole cell configuration. In addition to their effect to inhibit peak I(Na), acute application of DHA and EPA blocked veratridine-induced late sodium current (late I(Na-Verat)) in a concentration--dependent manner with IC(50) values of 2.1 +/- 0.5 microM and 5.2 +/- 0.8 microM,for DHA and EPA, respectively. Channels availability was reduced, resulting in a significant leftward shift of the steadystate inactivation curve by -10.0 +/- 2.1 mV and -8.5 +/- 0.2 mV for DHA and EPA, respectively. Similar inhibitory effects of DHA and EPA were also observed on late I(Na-KPQ). In addition to their role as blocking agents of peak I(Na), DHA and EPA reduced human late I(Na). These results could explain the antiarrhythmic properties of DHA and EPA during ischemia or following ischemia-reperfusion.
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PMID:Direct protective effects of poly-unsaturated fatty acids, DHA and EPA, against activation of cardiac late sodium current: a mechanism for ischemia selectivity. 1789 22

Dehydroepiandrosterone sulphate is one of the most important neurosteroids. In the present paper, we studied the effect of dehydroepiandrosterone sulphate on persistent sodium currents and its mechanism and functional consequence with whole-cell patch clamp recording method combined with a pharmacological approach in the rat medial prefrontal cortex slices. The results showed that dehydroepiandrosterone sulphate inhibited the amplitude of persistent sodium currents and the inhibitory effect was significant at 0.1 microM, reached maximum at 1 microM and decreased with the increase in the concentrations of above 1 microM. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was canceled by the Gi protein inhibitor and the protein kinase C inhibitor, but not by the protein kinase A inhibitor. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was also canceled by the sigma-1 receptor blockers and the sigma-1 receptor agonist could mimic the effect of dehydroepiandrosterone sulphate. Dehydroepiandrosterone sulphate had no significant influence on neuronal excitability but could significantly inhibit chemical inhibition of mitochondria-evoked increase in persistent sodium currents. These results suggest that dehydroepiandrosterone sulphate inhibits persistent sodium currents via the activation of sigma-1 receptors-Gi protein-protein kinase C-coupled signaling pathway, and the main functional consequence of this effect of DHEAS is presumably to protect neurons under ischemia.
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PMID:Neurosteroid dehydroepiandrosterone sulphate inhibits persistent sodium currents in rat medial prefrontal cortex via activation of sigma-1 receptors. 1803 54

Basic and clinical evidence suggests that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) decrease fatal arrhythmias and infarct sizes. This study investigated if pericardial delivery of n-3 PUFAs would protect the myocardium from ischemic damages and arrhythmias. Acute myocardial infarctions were induced in 23 pigs with either 45 min balloon inflations or clamp occlusions of the left anterior descending coronary arteries and 180 min reperfusion. Docosahexaenoic acid (C22:6n-3, DHA, 45 mg), one of the main n-3 PUFAs in fish oil, was infused within the pericardial space only during the 40-min stabilizing phase, 45 min ischemia and initial 5 min reperfusion. Hemodynamics and cardiac functions were very similar between the DHA-treated and control groups. However, DHA therapy significantly reduced infarct sizes from 56.8 +/- 4.9% for controls (n = 12) to 28.8 +/- 7.9% (P < 0.01) for DHA-treated animals (n = 11). Compared with controls, DHA-treated animals significantly decreased heart rates and reduced ventricular arrhythmia scores during ischemia. Furthermore, three (25%) control animals experienced eight episodes of ventricular fibrillation (VF), and two died subsequent to unsuccessful defibrillation. In contrast, only 1 (9%) of 11 DHA-treated pigs elicited one episode of VF that was successfully converted via defibrillation to normal rhythm; thus, mortality was reduced from 17% in the controls to 0% in the DHA-treated animals. These data demonstrate that pericardial infusion of n-3 PUFA DHA can significantly reduce both malignant arrhythmias and infarct sizes in a porcine infarct model. Pericardial administration of n-3 PUFAs could represent a novel approach to treating or preventing myocardial infarctions.
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PMID:Pericardial delivery of omega-3 fatty acid: a novel approach to reducing myocardial infarct sizes and arrhythmias. 1832 93


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