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)

A previously validated small mammal trauma model, hindlimb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to investigate the effects of traumatic injury on two of the major hepatic enzymes of detoxification, glutathione S-transferase and epoxide hydrolase. Hepatic cytosolic glutathione S-transferase activity toward a variety of substrates showed a 26-34% decrease at 24 hr after model injury. Hepatic microsomal epoxide hydrolase activity toward 1,2-epoxy-3-(p-nitrophenoxy)propane was diminished by 53% after model trauma. Both enzymatic activities toward styrene oxide were similarly depressed. The toxicological sequelae of these derangements were illustrated by administering a dose of styrene oxide (300 mg/kg, ip) which was below the threshold dose (350 mg/kg, ip) necessary to produce hepatotoxicity in control animals. Model trauma dramatically enhanced the hepatotoxic effects of the subthreshold dose, as well as the covalent binding of labeled styrene oxide to liver proteins. These findings indicate that traumatic injury renders the animal more susceptible to agents which are detoxified by glutathione S-transferase and epoxide hydrolase. Conversely, model trauma provided almost complete protection from the hepatotoxic effects of a standard dose (200 mg/kg, ip) of bromobenzene. This protection appeared to derive from a post-traumatic alteration of cytochrome P-450 subpopulations that decreased the formation of the potentially toxic 3,4-epoxide metabolite, despite an increase in the cytochrome P-448-mediated generation of the nontoxic 2,3-epoxide. For bromobenzene, the change in cytochrome P-450-mediated activation appeared quantitatively more significant in overall toxicity than the post-traumatic depression of detoxification pathways described above, leading to decreased toxicity in vivo. For other compounds, the combination of post-traumatic influences on cytochrome P-450/P-448 activity and epoxide hydrolase/glutathione S-transferase activities could lead to markedly enhanced toxicity.
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PMID:Effects of model traumatic injury on hepatic drug metabolism in the rat. VI. Major detoxification/toxification pathways. 289 98

This study examined whether brief repeated myocardial ischemia altered free radical generating and scavenging activity in a dog model. In dogs preconditioned with four 5-min left anterior descending coronary artery (LAD) occlusions and reperfusions, we examined transcardiac changes in both the function of neutrophils, cells which are major free radical generators, and in myocardial antioxidant enzyme activity, as an indication of free radical scavenging. Neutrophil function was assessed by determining luminol-enhanced whole blood chemiluminescence (CL) induced by zymosan. Blood was taken simultaneously from the carotid artery and the cardiac vein running along the occluded LAD. Preconditioning with sublethal ischemia significantly reduced whole blood CL in the cardiac vein compared with the carotid artery after the first and fourth 5-min reperfusions, while there was no difference in neutrophil count between these sampling sites. Immediately after brief repeated ischemia and reperfusion, manganese-superoxide dismutase (SOD) activity was significantly enhanced, and glutathione reductase activity was markedly reduced in the ischemic, compared with the non-ischemic, myocardium. There were no differences in the myocardial activities of copper, zinc-SOD, glutathione peroxidase, and glutathione S-transferase between the ischemic and non-ischemic regions. Also, no difference was observed between the reduced myocardial glutathione levels in these regions, although the oxidized glutathione level was significantly higher in the ischemic regions of the subepicardial and subendocardial areas. We demonstrated that brief repeated ischemia affects free radical generating and scavenging systems in the ischemic myocardium.
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PMID:Brief myocardial ischemia affects free radical generating and scavenging systems in dogs. 840 20

The biochemical adaptations of cellular antioxidant defenses that permit anoxia-tolerant animals to deal effectively with rapid and large changes in oxygen availability, and hence oxidative stress, during transitions from anoxia to normoxia provide insights into the strategies of antioxidant defense that could help to minimize reperfusion injuries to mammalian organs after anoxia/ischemia stress. The present study analyzes the effects of 30 h anoxia exposure followed by reoxygenation on the antioxidant defenses (activities of five enzymes, glutathione status) and lipid peroxidation damage to organs of the leopard frog Rana pipiens (5 degrees C-adapted autumn frogs). Exposure to 30 h anoxia resulted in significant increases in the activities of skeletal muscle and heart catalase (by 53 and 47%), heart and brain glutathione peroxidase (by 75 and 30%), and brain glutathione S-transferase (by 66%). In most cases, enzyme activities had returned to the control values after 40 h aerobic recovery. Activities of superoxide dismutase and glutathione reductase were unaltered in all of the organs, and anoxia/recovery had no effect on any of the enzymes in liver. Glutathione equivalents (GSH-eq) were maintained in four organs during anoxia but decreased by 32% in brain during anoxia. Brain GSH-eq had recovered after 90 min reoxygenation, and, in addition, hepatic GSH-eq rose by 71% after 90 min reoxygenation. The ratio of oxidized glutathione to GSH-eq was also affected by anoxia in an organ-specific way. Lipid peroxidation, assessed as the content of thiobarbituric acid-reactive substances (TBARS), was unaltered in skeletal muscle and liver after 30 h anoxia exposure or short (25 and 90 min)- or long-term (40 h) periods of reoxygenation, indicating that cycles of natural and survivable anoxia/reoxygenation occur without significant increase in TBARS in selected organs. Overall, the data demonstrate that elements of the antioxidant system of R. pipiens are induced during anoxia exposures as a possible preparation for dealing with potentially harmful oxygen reperfusion stress.
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PMID:Relationship between anoxia exposure and antioxidant status in the frog Rana pipiens. 889 82

Donor pretreatment is a new concept in organ preservation. Pentoxifylline (PTX) has been reported to suppress the activation of Kupffer cells and to decrease injury to the hepatic graft after rat liver transplantation. We evaluated the efficiency of PTX pretreatment on the donor against hepatic injury following cold ischemia (CI) or warm ischemia (WI) using the rat liver transplantation model. Dose dependency: every rat was injected intraperitoneally with PTX (30, 50, or 80 mg/kg) or saline. One hour later, the portal vein (PV) and the hepatic artery (HA) were clamped for 30 min. Transplantation: the donor rat was injected intraperitoneally with 50 mg/kg PTX or saline, 1 hr before laparotomy. Animals were divided into two groups. In the CI group, grafts were preserved for 12 hr in University of Wisconsin solution at 4 degrees C and transplanted. In the WI group, the PV and the HA in the donor were clamped for 30 min before donor surgery, and the grafts were transplanted. Serum levels of tumor necrosis factor-alpha (TNF-alpha), glutathione S-transferase-alpha (GST-alpha), and aspartate transaminase (AST) were measured at 30 min, 3 hr, and 24 hr after reperfusion of the PV. Compared with those of a control group, the serum levels of TNF-alpha, GST-alpha, and AST in the PTX-pretreated groups were significantly lower after both CI and WI at 30 min and further suppressed in the WI group at 24 hr. These results indicate that PTX pretreatment on the donor is effective for suppression of hepatic injury after both CI and WI.
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PMID:Efficiency of pentoxifylline in donor pretreatment in rat liver transplantation. 935 39

Transient sublethal hyperthermia and the recovery from this exposure to heat (heat shock preconditioning) provides a cytoprotective effect on oxidative insults through an intracellular protective response, heat shock response. The impact of heat shock preconditioning on hepatic microvascular failure, which is a causative determinant of ischemia/reperfusion-induced injury of the liver, was investigated by using intravital fluorescence microscopy. In Sprague-Dawley rats, normothermic ischemia was induced by totally clamping the hepatoduodenal ligament for 20 min, followed by 120 min of reperfusion. Heat shock preconditioning was performed by whole-body hyperthermia (42 degrees C for 15 min) and subsequent 48 h recovery. In accordance with the prominent induction of heat shock protein 70 in the liver tissue, the postischemic decrease in sinusoidal perfusion rate and sinusoidal diameter, and the postischemic increase in the number of stagnant leukocytes in sinusoids and adherent leukocytes in postsinusoidal venules were significantly attenuated in the heat shock-treated animals. Furthermore, liver enzyme release (glutamate pyruvate transaminase and alpha-glutathione S-transferase) was significantly reduced and postischemic deterioration of bile production was attenuated. The 7-day survival rate after 20-minute ischemia was significantly improved from 50% to 80% (heat shock-nontreated group vs. heat shock-treated group, P < 0.05). These results indicate that heat shock preconditioning attenuates ischemia/reperfusion-induced hepatic injury by preventing postischemic microvascular disturbances, and that its protective effect is circumstantially associated with the concomitant induction of heat shock protein 70.
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PMID:Reduction of hepatic microcirculatory failure caused by normothermic ischemia/reperfusion-induced injury by means of heat shock preconditioning. 1056 6

This study was designed to elaborate a molecular profile of expressed genes during ischemic injury to the mouse heart after surgical constriction of the left coronary artery without reperfusion. A mouse cDNA array containing 588 known genes was used to compare gene expression in heart RNA after 24-h ischemia with control tissue. Alterations in gene expression on the array were supported by relative reverse transcription-polymerase chain reaction analysis after timed periods of ischemia. Decreased levels of the cell cycle regulator p18ink4 and the oxidative responsive gene glutathione S-transferase were accompanied by an upregulation of the genes associated with cardiac muscle development, alpha-myosin heavy chain and fetal myosin alkali light chain. Other stress responses elicited by cardiac injury included an induction of Egr-1 and Egr-3 transcription factors, as well as the apoptotic regulator Bax. Altogether, these findings indicate that expression of genes associated with a fetal transcription program may be involved with the post ischemic remodeling process in heart ventricles.
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PMID:Gene expression profile in mouse myocardium after ischemia. 1101 87

Liver steatosis is frequently encountered at organ harvest and, although functionally inapparent in the donor, may seriously affect the functional recovery of the graft after ischemic preservation. The present study was aimed to investigate the diagnostic value of alpha-glutathione S-transferase (GST) in non-ischemic and ischemic livers with or without compensated steatosis. A histologically documented mild to moderate steatosis was induced in livers of male Wistar rats by fasting for 2 days and subsequent feeding of a fat-free diet enriched in carbohydrates. Fatty livers (FL) were retrieved and perfused in vitro for 45 min either immediately or after ischemic preservation at 4 degrees C in HTK solution. Effluate was collected during isolated perfusion and later analysed for liver specific enzymes, including GST. Normal livers (NL) were excised from healthy rats and underwent the same protocol. Non-ischemic livers showed similar enzyme release (FL versus NL) for ALT or GLDH but significant differences in GST. After ischemic preservation of NL, enzyme release increased mildly with respect to the non-ischemic reference values for ALT, remained unchanged for GLDH and rose substantially for GST. In FL, there was a more than 10-fold increase in all parameters, being most pronounced for GLDH as a marker of mitochondrial damage. It is concluded that GST may discriminate between healthy and suboptimal steatotic livers prior to ischemia and that the release of GST upon postischemic reperfusion of normal livers proves to be the most sensitive indicator for hepatocellular injury. However, GST turned out to be less useful for the detection of postischemic reperfusion injury in steatotic grafts.
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PMID:Value of alpha glutathione S-transferase for in vitro evaluation of preservation injury in normal and steatotic livers. 1111 71

Injury during the transplant process affects the alloantigen-dependent factors and the alloantigen-independent processes of "chronic" rejection. Consequently, the determination of reliable parameters for the assessment of ischemic damage is essential for the prediction of renal changes after ischemia/reperfusion injury. The aim of this study was to assess the ability of (1)H NMR spectroscopy to predict the early graft dysfunction in an ischemia/reperfusion model after preservation in two standard preservation solutions, Euro-Collins (EC) and University of Wisconsin (UW). The second aim was to specify the role of the UW solution in preventing renal medullary injury. Urine and plasma samples from three experimental groups were examined during 2 weeks: control group (n = 5), EC group (cold flushed and 48-h cold storage of kidney in EC and autotransplantation, n = 12), and UW group (cold flushed and 48-h cold storage of kidney in UW and autotransplantation; n = 12). We also examined these kidneys 30-40 min after implantation and on the sacrifice day. Creatinine clearance was significantly reduced in the EC group during the second week. Fractional excretion of sodium and urine N-acetyl-beta-d-glucosaminidase activity were improved but not significantly different in the preserved groups. Urinary concentrations of the alpha-class glutathione S-transferase were significantly greater in the EC group during the first week after transplantation. The most relevant resonances for evaluating renal function after transplantation determined by (1)H NMR spectroscopy were those arising from citrate, dimethylamine (DMA), lactate, and acetate in urine and trimethylamine-N-oxide (TMAO) in urine and plasma. These findings suggest that graft dysfunction is associated with damage to the renal medulla determined by TMAO release in urine and plasma associated with DMA and acetate excretion. Citrate is also a urinary marker that can discriminate kidneys with a favorable evolution. Our results suggest that (1)H NMR spectroscopy is an efficient technique for detecting ischemic damage when accurate and precise data on graft injury is required. In addition, this study outlines the specific impact of the UW solution against injury to the renal medulla.
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PMID:Noninvasive monitoring of citrate, acetate, lactate, and renal medullary osmolyte excretion in urine as biomarkers of exposure to ischemic reperfusion injury. 1122 25

The liver injury was induced by intestinal ischemia-reperfusion and the protective effect of erigeron injection (EI) was studied in mice. The results showed that serum alanine transaminase (ALT) and glutathione S-transferase (GST) activity increased while the root of superior mesenteric artery was blocked with non-injury artery clap for 20 minute and reperfusion for 1 hour. EI could protect the above changes induced by intestinal ischemia-reperfusion. EI could reduce the activities of serum ALT and GST, decrease the content of hepatic MDA and significantly increase the activity of SOD. The pathological changes of hepatocytes induced by intestinal ischemia-reperfusion were less in EI groups. These results suggested that EI could protect the liver of mice from injury induced by intestinal ischemia-reperfusion. One of the mechanisms of hepatoprotective action was related to the antioxidative function of erigeron.
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PMID:[Protective effect of erigeron injections on hepatotoxicity induced by intestinal ischemia-reperfusion in mice]. 1132 58

This study examined the effects of 1 degrees C hypo- or hyperthermia on in vivo liver ischemia and reperfusion (I/R) injury in 15 fasted male Wistar rats. Rats were ventilated, and rectal temperature was maintained at 36, 37 (normothermic), or 38 degrees C. In all rats, 70% liver ischemia was induced by clamping the afferent vessels to the median and left lateral lobes for 60 min, and reperfusion was allowed for 90 min. Changes in plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alpha-glutathione S-transferase (alpha-GST) levels were measured, hemodynamics and bile secretion were monitored, and arterial blood-gas analysis was performed. All ventilated rats showed a normal pH, arterial PCO(2), and arterial PO(2). AST, ALT, and alpha-GST levels were significantly higher in the 38 degrees C group when compared with the 36 and 37 degrees C groups after ischemia. No differences in bile secretion were found between all groups. Histopathological alterations were in agreement with AST, ALT, and alpha-GST levels in plasma. We conclude that a decrease of only 1 degrees C in body temperature significantly attenuates liver I/R injury, whereas an increase of 1 degrees C significantly increases liver I/R injury.
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PMID:Pronounced effect of minor changes in body temperature on ischemia and reperfusion injury in rat liver. 1140 39


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