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

The role of stress-activated protein kinases (SAPKs), c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase, in preconditioning (PC) was examined with the use of isolated rat hearts subjected to four cyclic episodes of 5-min ischemia and 10-min reperfusion followed by 30-min ischemia and 2-h reperfusion (I/R). A group of hearts was preperfused with 100 microM curcumin, a c-Jun and JNK1 inhibitor, or 5 microM SB 203580, a p38 MAP kinase inhibitor. Another group of hearts was preperfused with 20 microM anisomycin, a stimulator for both JNK and p38 MAP kinases. I/R increased the protein levels of JNK1, c-Jun, and p38 MAP kinase. PC also enhanced the induction of these kinases, but subsequent I/R-mediated increase was blocked by PC. Curcumin blocked I/R- and PC-mediated increase in JNK1 and c-Jun protein levels, whereas it had no effects on p38 MAP kinase. SB 203580, on the other hand, was equally effective in reducing the p38 MAP kinase activation but exerted no effects on JNK1 and c-Jun induction. I/R-mediated increased myocardial infarction was reduced by any of the following compounds: anisomycin, curcumin, and SB 203580. The cardioprotective effects of PC were abolished by either curcumin or SB 203580. The results demonstrate that PC is mediated by a signal-transduction pathway involving both JNK1 and p38 MAP kinase. Activation of SAPKs, although transient, is obligatory for PC.
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PMID:SAPKs regulation of ischemic preconditioning. 1099 48

Inflammatory cytokines interleukin 1 (IL-1), IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha) have been recognized as important mediators of pathophysiological and immunological events associated with shock. These inflammatory events after hemorrhage and resuscitation are characterized by the activation of transcription regulators such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Curcumin, an anti-inflammatory remedy used in Indian medicine, is known to suppress NF-kappaB and AP-1 activation and also to reduce ischemia-reperfusion injuries in animal models. Therefore, the aim of this study was to determine whether administration of curcumin before hemorrhagic shock has any salutary effects on cytokines and the redox-sensitive transcription factors NF-kappaB and AP-1. mRNA levels of IL-1alpha, IL-1beta, IL-2, IL-6, IL-10, and TNF-alpha were determined by reverse transcriptase-polymerase chain reaction in rat livers collected at 2 and 24 h after hemorrhage/resuscitation. The effect of curcumin on the activation of NF-kappaB and AP-1 was determined by electrophoretic mobility shift assays. Significant increases in the levels of liver cytokines IL-1alpha, IL-1beta, IL-2, IL-6, and IL-10 were observed in the 2-h posthemorrhage/resuscitation group compared with sham animals. In contrast, oral administration of curcumin for 7 days followed by hemorrhage/resuscitation regimen resulted in significant restoration of these cytokines to depleted levels, and, in fact, IL-1beta levels were lower than sham levels. Also, the 24-h postresuscitation group showed similar patterns with some exceptions. NF-kappaB and AP-1 were differentially activated at 2 and 24 h posthemorrhage and were inhibited by curcumin pretreatment. Serum aspartate transaminase estimates indicate decreased liver injury in curcumin-pretreated hemorrhage animals. These results suggest that protection against hemorrhage/resuscitation injury by curcumin pretreatment may result from the inactivation of transcription factors involved and regulation of cytokines to beneficial levels.
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PMID:Differential regulation of cytokines and transcription factors in liver by curcumin following hemorrhage/resuscitation. 1257 24

Free radical induced neuronal damage is implicated in cerebral ischemia reperfusion (IR) injury and antioxidants are reported to have neuroprotective activity. Several in vitro and in vivo studies have proved the antioxidant potential of curcumin and its metabolites. Hence, in the present study the neuroprotective potential of curcumin was investigated in middle cerebral artery occlusion (MCAO) induced focal cerebral IR injury. 2 h of MCAO and 22 h of reperfusion resulted in the infarct volume of 210.39 +/- 31.25 mm3. Administration of curcumin 100 and 300 mg/kg, i.p. 30 min. after MCAO produced 37.23 +/- 5.10% and 46.39 +/- 10.23% (p < 0.05) reduction in infarct volume, respectively. Ischemia induced cerebral edema was reduced in a dose dependent manner. Curcumin at 300 mg/kg, i.p. produced 50.96 +/- 6.04% reduction in edema (p < 0.05) volume. Increase in lipid peroxidation after MCAO in ipsilateral and contralateral hemisphere of brain was observed, which was reduced by curcumin (300 mg/kg, i.p.)-treatment. Decrease in superoxide dismutase and glutathione peroxidase activity was observed in ipsilateral hemisphere of MCAO animal. Curcumin-treatment (300 mg/kg, i.p.) prevented IR injury mediated fall in glutathione peroxide activity. Peroxynitrite measured using rhodamine123 fluorescence and anti-nitrotyrosine immunofluorescence indicated increased peroxynitrite formation after IR insult. Curcumin-treatment reduced peroxynitrite formation and hence the extent of tyrosine nitration in the cytosolic proteins. These results suggest the neuroprotective potential of curcumin in cerebral ischemia and is mediated through its antioxidant activity.
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PMID:Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats. 1467 54

The present study was undertaken to evaluate the cardioprotective potential of Curcuma longa (Turmeric) in the ischemia-reperfusion (I/R) model of myocardial infarction (MI). Wistar rats were divided into three groups and received saline orally (sham, control I/R group) and Curcuma longa 100 mg/kg (CL-100 treated group) respectively for one month. On the 31st day, rats of the control I/R and Cl treated groups were subjected to 45 min of occlusion of the LAD coronary artery and were thereafter reperfused for 1 h. I/R resulted in significant cardiac necrosis, depression in left ventricular function, decline in antioxidant status and elevation in lipid perodixation in the control I/R group as compared to sham control. Myocardial infarction produced after I/R was significantly reduced in the Cl treated group. Cl treatment resulted in restoration of the myocardial antioxidant status and altered hemodynamic parameters as compared to control I/R. Furthermore, I/R-induced lipid peroxidation was significantly inhibited by Cl treatment. The beneficial cardioprotective effects also translated into the functional recovery of the heart. Cardioprotective effect of Cl likely results from the suppression of oxidative stress and correlates with the improved ventricular function. Histopathological examination further confirmed the protective effects of Cl on the heart.
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PMID:Protective effects of Curcuma longa on ischemia-reperfusion induced myocardial injuries and their mechanisms. 1526 70

Increased oxidative stress has been regarded as an important underlying cause for neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. In recent years, there has been increasing interest in investigating polyphenols from botanical source for possible neuroprotective effects against neurodegenerative diseases. In this study, we investigated the mechanisms underlying the neuroprotective effects of curcumin, a potent polyphenol antioxidant enriched in tumeric. Global cerebral ischemia was induced in Mongolian gerbils by transient occlusion of the common carotid arteries. Histochemical analysis indicated extensive neuronal death together with increased reactive astrocytes and microglial cells in the hippocampal CA1 area at 4 days after I/R. These ischemic changes were preceded by a rapid increase in lipid peroxidation and followed by decrease in mitochondrial membrane potential, increased cytochrome c release, and subsequently caspase-3 activation and apoptosis. Administration of curcumin by i.p. injections (30 mg/kg body wt) or by supplementation to the AIN76 diet (2.0 g/kg diet) for 2 months significantly attenuated ischemia-induced neuronal death as well as glial activation. Curcumin administration also decreased lipid peroxidation, mitochondrial dysfunction, and the apoptotic indices. The biochemical changes resulting from curcumin also correlated well with its ability to ameliorate the changes in locomotor activity induced by I/R. Bioavailability study indicated a rapid increase in curcumin in plasma and brain within 1 hr after treatment. Together, these findings attribute the neuroprotective effect of curcumin against I/R-induced neuronal damage to its antioxidant capacity in reducing oxidative stress and the signaling cascade leading to apoptotic cell death.
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PMID:Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits. 1607 66

Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model.
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PMID:Anti-ischemic effect of curcumin in rat brain. 1820 70

The antioxidant activity of C.oil in cerebral stroke has been reported earlier. We have attempted here to clarify the mechanisms underlying the neuroprotection against experimental cerebral ischemia by Curcuma oil (C.oil), isolated from the rhizomes of Curcuma longa. C.oil (250 mg/kg i.p.) was given 30 min before focal ischemia in rats caused by occlusion of the middle cerebral artery (1h of occlusion, 24h of reflow). Ischemia, leads to elevation in [Ca(2+)] this sets into motion a cascades of ischemic injury which was attenuated by C.oil. C.oil reduced post-ischemic brain neutrophil infiltration in the ischemic area, controlled tissue NOx levels and the neuronal levels of nitric oxide, peroxynitrite and reactive oxygen species when measured after 24h of reflow. Double immunofluorescence staining analysis and Western immunoblot analysis with C.oil treatment showed that the expression of nitric oxide synthase (NOS) isoforms were decreased significantly compared to the untreated ischemia group. Ischemia is associated with increased in TUNEL (TdT-mediated dUTP nick-end labeling) positive cells in brain sections indicating DNA fragmentation. The C.oil treated group showed a significant decrease in numbers of apoptotic cells compared to the untreated ischemia group, as seen in the flowcytometric analysis of the neurons. Results of immunohistochemistry and Western immunoblot indicate that C.oil suppressed the elevated protein level of Bax, and aided mitochondrial translocation and activation of Bcl-2 by altered mitochondrial membrane potential. It also inhibits the cytosolic release of apoptogenic molecules like cytochrome c, inhibits the activation of caspase-3 and the expression of p53 ultimately inhibiting apoptosis. Our observations suggest that high levels of NO generated by NOS isoforms are partially responsible for exacerbating the neuronal damage induced by MCAo by intraluminal filament.
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PMID:Curcuma oil modulates the nitric oxide system response to cerebral ischemia/reperfusion injury. 1848 79

Curcumin (diferuloylmethane), an active ingredient of turmeric, obtained from the powdered rhizomes of Curcuma longa Linn., has been traditionally recognized for treatment of several diseases. To evaluate the potential clinical use of curcumin, we determined the dose dependence of its effects in the therapeutic window and of the neuroprotective efficacy in a cerebral thromboembolic model of the rat. Rats were subjected to occlusion of the middle cerebral artery (MCAo) by a thrombus and treated with different doses of curcumin or the vehicle at 4h after ischemia. The animals were assessed after 24h for motor performance and neurological deficit. The rats were sacrificed immediately afterwards for evaluation of infarct, edema volume, estimation of nitrate and nitrite levels, neutrophil infiltration and levels of GSH and glutathione peroxidase (GSH-Px) in brain tissue. Curcumin reduced in a dose-dependent manner the ischemia-induced cerebral infarct and edema volume and attenuated neurological deficits observed after 24h. Curcumin reduced post-ischemic brain neutrophil infiltration, nitrate and nitrite levels and ameliorated the loss of GSH-Px and tends to increase the GSH levels but not significantly in the brain tissue. Neuronal levels of reactive oxygen species, peroxynitrite, and nitric oxide were lowered and in brain cryosections inducible nitric oxide synthase expression were significantly inhibited after treatment with curcumin. The present study is the first evidence of effectiveness of curcumin when given 4h post-ischemia in the rat thromboembolic stroke models, as it reduces infarct volume, ameliorates the sensory motor function and significantly attenuated the nitrosative stress.
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PMID:Dose dependence and therapeutic window for the neuroprotective effects of curcumin in thromboembolic model of rat. 1861 16

In this study we explored the effects of curcumin in cardiac cells subjected to a protocol simulating ischemia-reperfusion (IR). Curcumin (10 microM) was administered before ischemia (pretreatment) or at the moment of reperfusion (posttreatment) and its effects were compared to those produced by a reference antioxidant (Trolox) with an equal antioxidant capacity. IR cardiac cells showed clear signs of oxidative stress, impaired mitochondrial activity, and a marked development of both necrotic and apoptotic processes; at the same time, increases in NF-kappaB nuclear translocation and JNK phosphorylation were observed. Curcumin pretreatment was revealed to be the most effective in attenuating all these modifications and, in particular, in reducing the death of IR cells. This confirms that the protective effect of curcumin is not related simply to its antioxidant properties but involves other mechanisms, notably interactions in the NF-kappaB and JNK pathways. These findings suggest that curcumin administration, in particular before the hypoxic challenge, represents a promising approach to protecting cardiac cells against IR injury. In this scenario our results point out the importance of the chronology for the outcome of the treatment and provide a differential valuation of the degree of protection that curcumin can exert by its antioxidant activity or by other mechanisms.
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PMID:Curcumin protects cardiac cells against ischemia-reperfusion injury: effects on oxidative stress, NF-kappaB, and JNK pathways. 1863 45

Curcumin (diferuoylmethane) is the active ingredient of turmeric (curcuma longa). There has been a surge of research in its anti-inflammatory and antioxidative properties, and its cardiovascular effects. A host of studies in in vitro and in vivo models of cardiac injury show that curcumin treatment reduces reactive oxygen species generation, monocyte adhesion to activated endothelial cells, and phosphorylation of c-Jun N-terminal kinase, p38 mitogen activated protein kinase and signal transducer and activator of transcription-3, and subsequent downstream signals. These alterations lead to preservation of myocardial function following ischemic or biochemical insult to the heart. Recent studies in models of pressure overload show that curcumin can reduce cardiac remodeling by altering reninangiotensin-system-transforming growth factor beta1 and collagen axis. Studies need to be done in humans to define the potential of curcumin in limitation of cardiac injury and preservation of cardiac function following ischemia.
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PMID:Currying the heart: curcumin and cardioprotection. 1915 99


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