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)

Reactive oxygen species are reactive, partly reduced derivatives of molecular oxygen. Important reactive oxygen species in biological systems include superoxide radical anion, hydrogen peroxide, and hydroxyl radical. Peroxynitrite, is another important species in biological systems. A variety of enzymatic and non-enzymatic processes can generate reactive oxygen species in mammalian cells. An extensive body of experimental evidence from studies using animal models supports the view that reactive oxygen species are important in the pathogenesis of ischemia-reperfusion syndromes, sepsis, acute respiratory distress syndrome, and multiple organ dysfunction syndrome. This view is further supported by data from clinical studies that correlate biochemical evidence of reactive oxygen species-mediated stress with the development of acute respiratory distress syndrome or sepsis in patients. Ethyl pyruvate, a simple derivative of pyruvic acid, has been shown to be efficacious in several animal models of critical illness, and warrants further evaluation in this regard.
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PMID:Reactive oxygen species as mediators of organ dysfunction caused by sepsis, acute respiratory distress syndrome, or hemorrhagic shock: potential benefits of resuscitation with Ringer's ethyl pyruvate solution. 1184 84

The glycolytic intermediate, pyruvate, is capable of scavenging reactive oxygen species (ROS). However, this compound is relatively unstable and hence is not useful as a therapeutic agent. Ethyl pyruvate, a simple derivative of pyruvate, appears to be more stable, and when formulated in a calcium-containing Ringer's-type balanced salt solution (REPS), has been shown to be salutary in rat models of two pathophysiological conditions--mesenteric ischemia/reperfusion and hemorrhagic shock/resuscitation--that are thought to be mediated, at least in part, by ROS. Because ROS also have been implicated in the pathogenesis of lipopolysaccharide (LPS)-induced shock, we carried out a series of experiments to determine if REPS is beneficial in this condition. Anesthetized rats were challenged with intravenous LPS (20 mg/kg). When mean arterial pressure (MAP) decreased to 60 mmHg, 3- to 5-mL boluses of either REPS (n = 10) or Ringer's lactate solution (RLS; n = 10) were infused as needed to prevent MAP from decreasing further. By design, the maximal volume of fluid infused was 7 mL/kg. Resuscitation with REPS as compared with RLS prolonged survival time (498 +/- 48 min vs. 362 +/- 30 min; P = 0.0014). Resuscitation with REPS as compared with RLS also was associated with significantly lower circulating concentrations of nitrite/nitrate and interleukin (IL)-6 and higher plasma levels of IL-10. These data support the view that delayed treatment with REPS modulates the inflammatory response to LPS, and prolongs survival time in a lethal model of endotoxic shock.
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PMID:Resuscitation with Ringer's ethyl pyruvate solution prolongs survival and modulates plasma cytokine and nitrite/nitrate concentrations in a rat model of lipopolysaccharide-induced shock. 1246 57

Reactive species of oxygen have been implicated as being important mediators in a variety of pathologic conditions, including burns, various forms of ischemia/reperfusion injury, and hemorrhagic shock. Pyruvate, an intermediate in the metabolism of glucose, is a potent reactive species of oxygen scavenger. Pyruvate, however, is unstable in aqueous solutions, and has not been developed as a therapeutic agent. Ethyl pyruvate, a simple derivative of the parent compound, is thought to be more stable in solution. Ringer's ethyl pyruvate solution (REPS) has been evaluated in a number of preclinical studies using animal models of mesenteric ischemia/reperfusion injury, hemorrhagic shock, and acute endotoxemia. Treatment with REPS, when compared with treatment with Ringer's lactate solution, has been shown to be able to improve survival and decrease expression of proinflammatory mediators. REPS warrants further evaluation for the resuscitation of patients with hemorrhagic shock.
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PMID:Ringer's ethyl pyruvate solution: a novel resuscitation fluid for the treatment of hemorrhagic shock and sepsis. 1276 16

Ethyl pyruvate (EP), a simple aliphatic ester of pyruvic acid, has been shown to improve survival and ameliorate organ damage in animal models of sepsis, ischemia/reperfusion injury and hemorrhagic shock. Incubating IL3-dependent mouse hematopoietic progenitor cell 32Dcl3 cells before or after irradiation with 10 mM EP increased resistance to radiation as assessed by clonogenic radiation survival curves, decreased release of mitochondrial cytochrome C into the cytoplasm, and decreased apoptosis. EP inhibited radiation-induced caspase 3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in 32Dcl3 cells in a concentration-dependent fashion. EP was given i.p. to C57BL/6NHsd mice irradiated with 9.75 Gy total-body irradiation (TBI). This treatment significantly improved survival. The survival benefit was apparent irrespective of whether treatment with EP was started 1 h before TBI and continued for 5 consecutive days after TBI or the compound was injected only 1 h before or only for 5 days after TBI. In all of the in vitro and in vivo experiments, ethyl lactate, an inactive analogue of EP, had no detectable radioprotective or mitigating effects. EP may be an effective radioprotector and mitigator of the hematopoietic syndrome induced by TBI.
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PMID:Ethyl pyruvate, a potentially effective mitigator of damage after total-body irradiation. 1797 49

Although, numerous studies have attempted to reduce the oxygen radical injury induced by the antioxidants in paraquat intoxication, these antioxidant therapies have showed few survival benefits. Ethyl pyruvate (EP) may function as an effective scavenger of oxygen radicals, an anti-inflammatory agent and an energy source in many ischemia reperfusion models. The aim of this study was to evaluate the antioxidant and anti-inflammatory effects of EP on the lung and the liver tissues in paraquat-intoxicated rats. Rats were randomly given either a low (2 mg/kg i.p.) or high (40 mg/kg i.p.) EP dose, 30 min before or 1 h after paraquat (50 mg/kg i.p.) administration, and subsequently killed at 6 and 24 h. Glutathione (GSH) and malondialdehyde (MDA) levels of the lungs and the livers, and plasma nitric oxide (NO) concentrations were measured. Pretreatment of EP significantly decreased the MDA level in the lung and the liver tissues. EP also significantly decreased plasma NO concentrations at 6 h. EP pretreatment, however, failed to show significant change in GSH concentration. In post-treatment of EP, MDA levels in the lung tissue and plasma NO levels were significantly decreased. In conclusion, EP decreased the lipid peroxidation and seemed to exert an anti-inflammatory action in the paraquat intoxication rat model.
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PMID:Protective effects of ethyl pyruvate treatment on paraquat-intoxicated rats. 1848 Jan 49

In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemia/reperfusion (I/R) in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff model. Twenty-four rats were randomly divided into 3 groups (n=8 in each group): control group was perfused for 120 min. In the I/R group, after 30 min stabilization the injury was induced by 30 min global ischemia followed by 60 min reperfusion. Ethyl pyruvate (EP) group was set up with the same protocol as I/R group except that it was supplied with 2 mmol/L EP 15 min before ischemia and throughout reperfusion. Myocardial malonaldehyde (MDA) content was measured. Myocardial apoptotic index (AI) was tested by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry. As compared with control group, the content of MDA, myocardial AI and the expression of Bcl-2, Bax proteins were increased significantly in I/R group, but the content of MDA, myocardial AI and the expression of Bax protein were decreased obviously and the expression of Bcl-2 protein was up-regulated in EP group (P<0.05). These results demonstrate that EP could inhibit apoptosis of cardiac myocytes possibly via alleviating oxidative stress, up-regulating Bcl-2 and down-regulating Bax proteins.
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PMID:Effects of ethyl pyruvate on myocardial apoptosis and expression of Bcl-2 and Bax proteins after ischemia-reperfusion in rats. 1856 23

Ethyl pyruvate is a simple derivative in Ca(+2)- and K(+)-containing balanced salt solution of pyruvate to avoid the problems associated with the instability of pyruvate in solution. It has been shown to ameliorate the effects of ischemia-reperfusion (I/R) injury in many organs. It has also been shown that I/R injury delays the healing of colonic anastomosis. In this study, the effect of ethyl pyruvate on the healing of colon anastomosis and anastomotic strength after I/R injury was investigated. Anastomosis of the colon was performed in 32 adult male Wistar albino rats divided into 4 groups of 8 individuals: (1) sham-operated control group (group 1); (2) 30 minutes of intestinal I/R by superior mesenteric artery occlusion (group 2); (3) I/R+ ethyl pyruvate (group 3), ethyl pyruvate was administered as a 50-mg/kg/d single dose; and (4) I/R+ ethyl pyruvate (group 4), ethyl pyruvate administration was repeatedly (every 6 hours) at the same dose (50 mg/kg). On the fifth postoperative day, animals were killed. Perianastomotic tissue hydroxyproline contents and anastomotic bursting pressures were measured in all groups. When the anastomotic bursting pressures and tissue hydroxyproline contents were compared, it was found that they were decreased in group 2 when compared with groups 1, 3, and 4 (P < .05). Both anastomotic bursting pressure (P = .005) and hydroxyproline content (P < .001) levels were found to be significantly increased with ethyl pyruvate administration when compared with group 2. When ethyl pyruvate administration doses were compared, a significant difference was not observed (P > .05). Ethyl pyruvate significantly prevents the delaying effect of I/R injury on anastomotic strength and healing independent from doses of administration.
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PMID:Ethyl pyruvate protects colonic anastomosis from ischemia-reperfusion injury. 1906 91

Ethyl pyruvate (EP), a simple aliphatic ester of pyruvic acid, has been shown to act as an anti-inflammatory molecule in various pathological conditions, which include sepsis or hemorrhagic shock. Recently, we showed that ethyl pyruvate has a neuroprotective effect in the postischemic brain and also in KA-induced pathogenesis in the brain. In this study, we examined whether aspirin augments neuroprotective effect of ethyl pyruvate in transient focal ischemia model by complementing the neuroprotective effects of ethyl pyruvate. Although, most of neuroprotective effect of aspirin has been attributed to the anti-platelet action, aspirin also has direct neuroprotective effects, including NF-kappaB inhibition. Ethyl pyruvate dose-dependently suppressed infarct formation in the postischemic brain, wherein intravenous administration of 5 mg/kg ethyl pyruvate 30 min after the occlusion reduced infarct volume to 34.5 +/- 15.5% (n = 6, P < 0.01) of that of the untreated control. In combination with aspirin (5 mg/kg, i.v.), the neuroprotective effect was enhanced, resulting in 16.0 +/- 5.9% (n = 6, P < 0.01) infarct volume. The time window for synergistic neuroprotection by ethyl pyruvate and aspirin extended to 9 h post-MCAO. The synergistic reduction in infarct volume was accompanied by suppression of the clinical manifestations associated with cerebral ischemia including motor impairment and neurological deficits. Inflammatory processes including microglial activation and proinflammatory cytokine expression were notably suppressed by the combination treatment in the postischemic brain and in primary microglia cultures, wherein ethyl pyruvate and aspirin modulate NF-kappaB signaling differentially. Aspirin interferes with IkappaB phosphorylation and degradation in the cytoplasm, possibly by specifically inhibiting IkappaB kinase-beta, whereas, the effect of ethyl pyruvate seems to occur in the nucleus, where it may interfere with the binding of NF-kappaB to responsive promoter elements in the target genes. Similar enhancement in neuroprotective effect was also observed in primary cortical cultures after NMDA or Zn(2+) treatment or oxygen-glucose deprivation. Together, these results indicate that combination treatment of ethyl pyruvate and aspirin affords synergistic neuroprotection in the postischemic brain with a wide therapeutic window, in part via differential modulation of the NF-kappaB signaling pathway.
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PMID:Combination treatment with ethyl pyruvate and aspirin enhances neuroprotection in the postischemic brain. 1963 61

High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia and reperfusion (I/R) injury. Ethyl pyruvate (EP), a potent reactive oxygen species scavenger, has been reported to inhibit myocardial apoptosis and reduce myocardial I/R injury. The aim of this study was to investigate the mechanism by which EP reduces myocardial I/R injury in rats. Anesthetized male rats were once treated with EP (50 mg/kg, i.p.) before ischemia, and then subjected to ischemia for 30 min followed by reperfusion for 4 h. Lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) activity and infarct size were measured. HMGB1 expression was assessed by immunoblotting. The results showed that pretreatment of EP (50 mg/kg) could significantly reduce the infarct size and the levels of LDH and CK after 4 h reperfusion (all P<0.05). EP could also significantly inhibit the increase of the MDA level, the decrease of the SOD level (both P<0.05). Meanwhile, EP could significantly inhibit the expression of HMGB1 induced by I/R. The present study suggested that ethyl pyruvate could attenuate myocardial I/R injury by inhibiting HMGB1 expression.
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PMID:Ethyl pyruvate reduces myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein in rats. 2155 72

Ethyl pyruvate (EP) has been reported to be neuroprotective in several models of brain injury, yet its influence on periventricular leukomalacia still remains elusive. Here we investigated whether repeated administration of EP could protect against white matter injury after hypoxia-ischemia (HI) (right common carotid artery ligation and 6 % O2 for 60 min) in post-natal 3 day rat pups. EP was injected (50 mg/kg, intraperitoneally) 10 min, 1 and 24 h after HI insult. Treatment with EP significantly reduced HI-induced ventricular enlargement, loss of developing oligodendrocytes, and hypomyelination. We further demonstrated a marked inhibitory effect of EP on inflammatory responses, as indicated by the decreased number of activated microglia and astrocytes and the reduced release of proinflammatory cytokines. Moreover, EP down-regulated the expression of cleaved caspase-3 and Bax, and up-regulated Bcl-2 expression after HI exposure. In conclusion, our results demonstrated that EP was able to provide potent protection on white matter injury through blocking the cerebral inflammatory responses and modulating the apoptotic death program of oligodendrocytes, indicating a potential neuroprotective agent in neonatal brain injury.
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PMID:Improvement of hypoxia-ischemia-induced white matter injury in immature rat brain by ethyl pyruvate. 2347 94


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