Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to evaluate the protective effect of palmatine, one of active ingredients of Coptidis rhizoma, against myocardial ischemia-reperfusion (I/R) injury is due to its antioxidant and anti-inflammatory action. Adult male rats were subjected to 30 min of ischemia and 6 or 24h of reperfusion. Rats were randomized to receive vehicle or palmatine 1h before reperfusion. Infarct size, myocardial function, and the antioxidant enzyme activity, such as malonaldehyde (MDA), lactate dehydrogenase (LDH), creatine phosphokinase (CK), superoxide dismutase (SOD) and catalase (CAT) were measured. Palmatine significantly improved I/R-induced myocardial dysfunction by increasing the values of the first derivative (+/-dp/dt) of left ventricular pressure and decreased infarct size by 50% (P<0.01 versus vehicle). As expected, palmatine markedly inhibited the increase of LDH, CK, and MDA contents in I/R rat serum, and it also significantly inhibited the decline of the activity of SOD and CAT in I/R cardiac tissues. In addition, COX-2 and iNOS expression in I/R myocardium was significantly reduced. Interestingly, palmatine increased heme oxygenase (HO)-1 induction in human aortic endothelial cells. We concluded that palmatine protects hearts from I/R injury in rats possibly by reducing oxidative stress and modulating inflammatory mediators.
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PMID:Palmatine from Coptidis rhizoma reduces ischemia-reperfusion-mediated acute myocardial injury in the rat. 1949 45

Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are neuroprotective in numerous models. Impairment of cerebrovascular reactivity (CR) contributes to ischemia/reperfusion (I/R)-induced neuronal damage. We tested whether PACAP and/or VIP preserve CR to I/R-sensitive dilator responses dependent on endothelial and/or neuronal function. Accordingly, changes in pial arteriolar diameters in response to hypercapnia (5-10% CO(2) ventilation) or topical N-methyl-d-aspartate (NMDA, 10(-4) M) were determined before and after I/R via intravital microscopy in anesthetized/ventilated piglets. Local pretreatment with non-vasoactive doses of PACAP (10(-8) M) and VIP (10(-9) M) prevented the attenuation of postischemic CR to hypercapnia; to 10% CO(2), the CR values were 27+/-8% vs 92+/-5% vs 88+/-13% (vehicle vs PACAP38 vs VIP, CR expressed as a percentage of the response before I/R, mean+/-SEM, n=8-8, p<0.05). PACAP, but not VIP, preserved CR to NMDA after I/R, with CR values of 31+/-10% vs 87+/-8% vs 35+/-12% (vehicle vs PACAP38 vs VIP, n=6-6). Unlike PACAP, VIP-induced vasodilation has not yet been investigated in the piglet. We tested whether VIP-induced arteriolar dilation was sensitive to inhibitors of cyclooxygenase (COX)-1 (SC-560, 1 mg/kg), COX-2 (NS-398, 1 mg/kg), indomethacin (5 mg/kg), and nitric oxide synthase (L-NAME, 15 mg/kg). VIP (10(-8)-10(-7)-10(-6) M, n=8) induced reproducible, dose-dependent vasodilation of 16+/-3%, 33+/-6%, and 70+/-8%. The response was unaffected by all drugs, except that the vasodilation to 10(-8) M VIP was abolished by SC-560 and indomethacin. In conclusion, PACAP and VIP differentially preserve postischemic CR; independent of their vasodilatory effect.
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PMID:PACAP and VIP differentially preserve neurovascular reactivity after global cerebral ischemia in newborn pigs. 1953 45

The aim of the present study was to compare the effects of genetic mPGES-1 loss and COX-2 inhibition on myocardial damage after coronary occlusion. mPGES-1(-/-) mice and their wild-type littermates were injected with vehicle or COX-2 inhibitor (celecoxib), and 30min later the left coronary artery was surgically occluded. At 24h, myocardial infarct (MI) volume was measured histologically. Post-MI survival was reduced in WT mice receiving celecoxib (12/20) compared with vehicle-treated controls (12/12) or the loss of mPGES-1 (13/13) together with increased phosphokinase (CPK) and cardiac troponin-I release. Endogenous mPGES-1 expression was unchanged by ischemia in WT mice and absent in mPGES-1(-/-) hearts. COX-2 expression was markedly increased at 24h after MI in WT hearts; this upregulation was largely attenuated in mPGES-1(-/-) mice. We conclude that loss of mPGES-1 prevents the upregulation of COX-2 after myocardial infarct, and in contrast to inhibition of COX-2, does not increase ischemic myocardial damage.
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PMID:Comparison of microsomal prostaglandin E synthase-1 deletion and COX-2 inhibition in acute cardiac ischemia in mice. 1955 11

Zileuton has been demonstrated to act as an anti-inflammatory agent by virtue of its well-known ability to inhibit 5-lipoxygenase (5-LO). However, the effects of zileuton on cardiovascular disease and cardiomyocyte apoptosis are unclear. Here, we investigated the effects of zileuton on apoptosis of cardiac myogenic H9c2 cells and neonatal rat cardiomyocytes (NRCMs), and examined the possible role of PKC delta-mediated induction of COX-2 in these effects. Treatment of H9c2 cells with zileuton efficiently induced COX-2 expression and PGE(2) biosynthesis in a time- and dose-dependent manner. Zileuton also exerted a profound protective effect against H(2)O(2)-induced oxidative stress, a mimic of reperfusion damage in vitro, and this protective effect was abolished by COX-2-selective inhibitor. When we investigated the signalling pathways involved in zileuton-induced COX-2 expression, we found that zileuton acts as a PKC delta activator, causing it to translocate from the cytosol to nucleus. Inhibition of PKC delta activation with rottlerlin, a PKC delta-specific inhibitor, abolished the zileuton-induced protection against H(2)O(2)-induced cell death and inhibited zileuton-induced COX-2 expression and PGE(2) production. The protective effect of zileuton was dramatically diminished by treatment with LY294002 or PD98059. Furthermore, zileuton-stimulated ERK1/2 and Akt phosphorylation was attenuated by rottlerin, indicating that PKC delta might act upstream of ERK1/2 and Akt. Moreover, inhibition of either ERK1/2 or Akt activation abolished zileuton-induced COX-2 expression. Knockdown of PKC delta with siRNA also reversed the protective effect of zileuton and blocked the induction of COX-2. These results suggest that zileuton-induced COX-2 expression is sequentially mediated through PKC delta-dependent activation of ERK1/2 and Akt. Based on these findings, we propose that zileuton might provide a new therapeutic strategy for ischemia/reperfusion injury of the heart.
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PMID:The cardioprotective effects of zileuton, a 5-lipoxygenase inhibitor, are mediated by COX-2 via activation of PKC delta. 1978 29

Oxidative and nitrosative stress are targets for intervention after ischemia/reperfusion. The aim of this study was to explore the effect of CR-6, a vitamin-E analogue that is antioxidant and scavenger of nitrogen-reactive species. Sprague-Dawley rats had the middle cerebral artery (MCA) occluded either for 90 mins or permanently. Cortical perfusion was continuously monitored by laser-Doppler flowmetry. CR-6 (100 mg/kg) was administered orally either at 2 and 8 h after MCA occlusion, or at 2 h only. Infarct volume, neurological deficit, and signs of reperfusion injury were evaluated. CR-6 was detected in plasma and brain by HPLC. CR-6 reduced glutathione consumption in the ischemic brain and superoxide generation in the isolated MCA. CR-6 decreased infarct volume and attenuated the neurological deficit at 1 and 7 days after ischemia/reperfusion, but not after permanent ischemia. Immediately after reperfusion, cortical blood flow values returned to their baseline (+/-20%) in several animals, whereas others showed hyper-perfusion (>20% of baseline). Reactive hyperemia was associated with adverse events such as increased cortical BBB leakage, edema, protein nitrotyrosination, COX-2 expression, and neutrophil accumulation; and with a poorer outcome, and CR-6 attenuated these effects. In conclusion, oral CR-6 administration after transient ischemia protects the brain from reperfusion injury.
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PMID:Antioxidant CR-6 protects against reperfusion injury after a transient episode of focal brain ischemia in rats. 1990 89

NADPH oxidase is an enzyme that converts molecular oxygen into reactive oxygen species, which cause severe damage in several organs. Cyclooxygenase (COX)-2 is an inducible enzyme that is important in gastric mucosal defense and repair processes. It is unclear whether NADPH oxidase is related to COX expression in the gastric mucosa, so we investigated the correlation. Under urethane anesthesia, a male Sprague Dawley rat stomach was mounted in an ex-vivo chamber, and ischemia/reperfusion (I/R) was performed through a cannula in the femoral vein. I/R significantly increased NADPH oxidase activity, H(2)O(2) production, and myeloperoxidase (MPO) activity. In contrast, ischemia alone clearly enhanced both NADPH oxidase activity and H(2)O(2) production but not MPO activity. Pretreatment with the NADPH oxidase inhibitor diphenylene iodonium (DPI) suppressed I/R-induced mucosal damage. On the other hand, the selective COX-2 inhibitor rofecoxib exhibited a tendency to enhance the severity of gastric damage induced by I/R, although the selective COX-1 inhibitor SC-560 and the nonselective COX inhibitor indomethacin had no effect. I/R also increased the expression of COX-2, and this increase was suppressed by pretreatment with DPI. These findings suggest that the increase in NADPH oxidase activity is involved in the occurrence of gastric mucosal damage induced by I/R and that this enzyme activity may be causally related to the upregulation of COX-2 during I/R.
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PMID:Roles of NADPH oxidase in occurrence of gastric damage and expression of cyclooxygenase-2 during ischemia/reperfusion in rat stomachs. 1994 2

OBJECTIVE-To identify expression and localization of cyclooxygenase (COX)-1 and COX-2 in healthy and ischemic-injured left dorsal colon of horses. SAMPLE POPULATION-Left dorsal colon tissue samples from 40 horses. PROCEDURES-Tissue samples that were used in several related studies on ischemia and reperfusion were evaluated. Samples were collected during anesthesia, before induction of ischemia, and following 1 hour of ischemia, 1 hour of ischemia and 30 minutes of reperfusion, 2 hours of ischemia, 2 hours of ischemia and 30 minutes of reperfusion, and 2 hours of ischemia and 18 hours of reperfusion. Histomorphometric analyses were performed to characterize morphological injury. Immunohistochemical analyses were performed to characterize expression and localization of COX-1 and COX-2. RESULTS-COX-1 and COX-2 were expressed in control tissues before ischemia was induced, predominantly in cells in the lamina propria. Ischemic injury significantly increased expression of COX-2 in epithelial cells on the colonic surface and in crypts. A similar significant increase of COX-1 expression was seen in the epithelial cells. CONCLUSIONS AND CLINICAL RELEVANCE-On the basis of information on the role of COX-2, upregulation of COX-2 in surface epithelium and crypt cells following ischemic injury in equine colon may represent an early step in the repair process.
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PMID:Expression of cyclooxygenase-1 and -2 in the left dorsal colon after different durations of ischemia and reperfusion in horses. 1995 Nov 26

A brief ischemic insult induces significant protection against subsequent massive ischemic events. The molecular mechanisms known as preconditioning (PC)-induced ischemic tolerance are not completely understood. We investigated whether kinetic changes of cyclooxygenase (COX)-2 during reperfusion time-periods after PC were related to ischemic tolerance. Rats were given PC by occlusion of middle cerebral artery (MCAO) for 10 min and sacrificed after the indicated time-periods of reperfusion (1, 2, 4, 8, 12, 18 or 24 h). In PC-treated rats, focal ischemia was induced by occlusion of MCA for 24 h and brain infarct volume was then studied to determine whether different reperfusion time influenced the damage. We report that the most significant protection against focal ischemia was obtained in rats with 8 h reperfusion after PC. Administration of indomethacin (10 mg/kg, oral) or rofecoxib (5 mg/kg, oral) 48 h prior to PC counteracted the effect of PC. Immunohistochemical analysis showed that COX-2 and HO-1 protein were induced in PC-treated rat brain, which was significantly inhibited by rofecoxib. Taken together, we concluded that the kinetic changes of COX-2 expression during the reperfusion period after PC might be partly responsible for ischemic tolerance.
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PMID:Kinetic Changes of COX-2 Expression during Reperfusion Period after Ischemic Preconditioning Play a Role in Protection Against Ischemic Damage in Rat Brain. 1996 67

HT008-1 is one of the prescriptions used in Traditional Korean Medicine for the treatment of mental and physical weakness. It is composed of Panax ginseng, Acanthopanax senticosus, Angelica sinensis and Scutellaria baicalensis, which have been reported to have various pharmacological effects on the central nervous system. The study investigated whether HT008-1 has neuroprotective effects in a focal cerebral ischemia rat model. Stroke was induced in rats by 2 h of middle cerebral artery occlusion (MCAo) followed by 22 h of reperfusion. HT008-1 (30, 100 and 300 mg/kg) and the component herbs (300 mg/kg) were administered orally twice at 0 and 2 h after ischemia. Oral administration of 300 mg/kg HT008-1 reduced brain infarction by 45.7%, prolonged the latency time by 24.8% in the rotarod test, and enhanced the score by 17.0% in the balance beam test. Only P. ginseng and S. baicalensis showed protective effects, and HT008-1 showed a greater effect than its component herbs. HT008-1 down-regulated the COX-2 and OX-42 expression in the penumbra region. In conclusion, the results show that HT008-1 may be effective in a rat stroke model by an antiinflammatory mechanism and may improve sensory-motor function by reducing damage in the cortex and caudoputamen.
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PMID:Neuroprotective effect of HT008-1, a prescription of traditional Korean medicine, on transient focal cerebral ischemia model in rats. 2014 7

Oleamide (cis-9-octadecenamide) is an endogenous sleep-inducing fatty acid amide that accumulates in the cerebrospinal fluid of the sleep-deprived animals. Microglia are the major immune cells involved in neuroinflammation causing brain damage during infection, ischemia, and neurodegenerative disease. In this study, we examined the effects of oleamide on LPS-induced production of proinflammatory mediators and the mechanisms involved in BV2 microglia. Oleamide inhibited LPS-induced production of NO and prostaglandin E2 as well as expression of iNOS and COX-2. We showed that oleamide blocked LPS-induced NF-kappaB activation and phosphorylation of inhibitor kappaB kinase (IKK). We also showed that oleamide inhibited LPS-induced phosphorylation of Akt, p38 MAPK, and ERK, activation of PI 3-kinase, and accumulation of reactive oxygen species (ROS). Finally, we showed that a specific antagonist of the CB2 receptor, AM630, blocked the inhibitory effects of oleamide on LPS-induced production of proinflammatory mediators and activation of NF-kappaB. Taken together, our results suggest that oleamide shows an anti-inflammatory effect through inhibition of NF-kappaB activation in LPS-stimulated BV2 microglia.
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PMID:Oleamide suppresses lipopolysaccharide-induced expression of iNOS and COX-2 through inhibition of NF-kappaB activation in BV2 murine microglial cells. 2029 53


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