Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-three canine hearts were isolated after initial cardioplegia and preserved for 6 hours in 4 degrees C saline solution with intermittent infusion of cardioprotective solution every hour. Reperfusion was observed for 2 hours under normothermic cross-circulation. Hearts were divided into five groups depending on the agent(s) added to the K(+)-Mg2+ cardioplegic solution (K(+)-Mg(2+)-CP) infused. Control hearts (n = 6) received K(+)-Mg(2+)-CP solution alone; group I (n = 7) received lidocaine, 200 mg/L, added to the K(+)-Mg(2+)-CP solution; group II (n = 7) received betamethasone (250 mg/L) added to the formula for group I; group III (n = 6) received diltiazem (200 micrograms/L) added to the formula for group II; group IV (n = 7) received aprotinin (150 KIU/L) added to the formula of group III. Coronary sinus MB fraction of creatine kinase level was significantly decreased at 60 and 120 minutes of reperfusion in group II, as was mitochondrial aspartate aminotransferase level at 2 hours of reperfusion. Lysosomal enzyme release decreased in group IV. Myocardial adenosine triphosphate levels and total adenine nucleotides showed no significant difference among the groups at the end of reperfusion; however, myocardial adenosine diphosphate and adenosine monophosphate levels during reperfusion increased significantly in group I, and myocardial adenosine diphosphate and adenosine monophosphate levels at the end of reperfusion in groups I and IV were significantly higher than those of the control. Calcium overload, which was lowest in group II, was not completely prevented during reperfusion in any group. Left ventricular end-systolic pressure volume relationship in group II showed the "best" functional recovery. In addition, the ultrastructure of the left ventricular myocardium was well preserved in all groups. These results suggest that membrane stabilization with lidocaine and betamethasone affords beneficial effects on myocardial biochemical and functional viability. Diltiazem appears to be less effective in preventing calcium overload during ischemia-reperfusion, and protease inhibition with aprotinin (150 KIU/ml) seems to be highly effective in suppressing lysosomal enzyme activation-release and maintaining myocardial adenosine diphosphate and adenosine monophosphate levels.
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PMID:Heart preservation: analysis of cardioprotective infusate characteristics. Membrane stabilization, calcium antagonism, and protease inhibition on myocardial viability: a biochemical, ultrastructural, functional study. 137 28

The cardiotoxic potential of the phenothiazine neuroleptic thioridazine and five of its metabolites, including two stereoisomeric forms of thioridazine 5-sulfoxide (ring sulfoxide), was characterized in the isolated perfused rat heart. Hearts from male Sprague-Dawley rats were perfused using a modified Langendorff technique. After a 30-min control period, hearts were perfused for 30 min with 15 or 30 microM thioridazine, racemic and isomeric forms of thioridazine 5-sulfoxide, or thioridazine 2-sulfoxide. Thioridazine disulfoxide, thioridazine 2-sulfone, and desmethylthioridazine 2-sulfoxide were perfused at 15 microM. Thioridazine (15 microM) severely reduced contractile tension and the rate of tension development (dT/dt), transiently increased coronary flow rate but prolonged conductance through the AV node. No arrhythmias were seen. At 30 microM, ventricular premature contractions and irregular rhythms occurred, progressing to asystole. Thioridazine 5-sulfoxide was arrhythmogenic at 15 and 30 microM. Atrial premature contractions and paroxysmal atrial tachycardia progressed to second degree AV block. Contractile tension and dT/dt declined although not as quickly when compared to thioridazine. Each isomeric form of thioridazine 5-sulfoxide was also cardiotoxic at 15 and 30 microM. There were minor differences in the onset and degree of toxicity but the overall results did not suggest a stereoselective effect. Lactic dehydrogenase and aspartate aminotransferase concentrations were unchanged after thioridazine 5-sulfoxide perfusion indicating no direct tissue damage. Thioridazine 5-sulfoxide induced arrhythmias could not be prevented or reversed by treatment with adrenergic agonists. They were reversible upon washout, however. The other metabolites were not arrhythmogenic at 15 microM. Racemic thioridazine 5-sulfoxide appears to be qualitatively and quantitatively more arrhythmogenic than thioridazine, an action that does not appear to be stereoselective.
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PMID:Cardiotoxicity of thioridazine and two stereoisomeric forms of thioridazine 5-sulfoxide in the isolated perfused rat heart. 376 35

The effects of aspartate (Asp) and 2-oxoglutarate (2-OG) on metabolism and function of isolated rat heart during hypoxia and reoxygenation were studied. Hearts were subjected to oxygenated perfusion with Krebs-Henseleit buffer supplied with 11 mM glucose (20 min) and anoxic perfusion with the buffer saturated with N2 (20 min), followed by reoxygenation (30 min). The substrate concentrations in the perfusate were 3.5 mM each. The additives had no effect on the energy metabolism and function of the oxygenated heart despite a two-fold rise in myocardial Asp and 2-OG. Substrate supplementation during anoxic perfusion resulted in reduced lactate dehydrogenase release and less depression of cardiac function. Prevention of Asp, glutamate, and 2-OG degradation in hypoxic myocardium was accompanied by relief of glycolytic flux and better preservation of ATP, phosphocreatine (PCr), and total creatine (Cr). Reoxygenation without the additives after supplemented anoxic perfusion failed to improve recovery of high-energy phosphates and cardiac function compared to control. However, during reoxygenation with the additives the treated hearts showed less cell membrane damage and enhanced recovery of contractile and pump function. These effects were associated with higher myocardial contents of ATP, PCr, and adenine nucleotides and a smaller Cr loss during reoxygenation. A more effective restoration of oxidative metabolism was related to promoted glucose oxidation due to replenishment of the malate-aspartate shuttle reactants. The results substantiate the use of substrates of cytosolic aspartate aminotransferase for myocardial protection against hypoxia/reoxygenation stress.
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PMID:Substrate accessibility to cytosolic aspartate aminotransferase improves posthypoxic recovery of isolated rat heart. 758 71

Oleuropein (oleu) is a natural phenolic antioxidant, which is present in elevated concentration in olives, olive oil and olive tree leaves. Doxorubicin (DXR) induced cardiotoxicity is mainly induced by oxidative stress but the precise mechanism remains obscure. However, there is evidence that high concentration of nitric oxide (NO) occurring as a result of iNOS induction and peroxynitrite formation may be involved in DXR cardiotoxicity. The aim of the present study was to evaluate a possible protective role of oleu in DXR induced cardiotoxicity in vivo. Fifty rats were divided into 6 groups and treated as follows: control group with a single injection of 2 ml normal saline intraperitoneally (i.p.), DXR group with a single dose of 20 mg/kg i.p, and DXR plus oleu groups with 20 mg/kg DXR i.p. and 100 or 200 mg/kg/BW of oleu i.p. for 5 or 3 consecutive days starting either 2 days before or on the day of DXR administration. Seventy-two hours after DXR treatment blood samples were collected for creatine phosphokinase (CPK), creatine phosphokinase-MB (CPK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) assessments and the rats were then sacrificed. Hearts were used for general histology, iNOS immunohistochemical and Western blot analysis, and for determination of tissue concentrations of lipid peroxidation products, protein carbonyls (PCs), and nitrotyrosine (NT). DXR treated animals demonstrated very extensive cytoplasmic vacuolisation whereas much less vacuolisation was found in oleu treated groups. They also revealed a significant elevation of cardiac enzymes release into systemic circulation (P<0.05 vs saline). Both doses of Oleu tested and both treatment protocols reduced DXR elevated serum levels of CPK, CPK-MB, LDH, AST and ALT (P<0.05). Furthermore, it reduced DXR induced lipid peroxidation, PCs content, NT concentration and iNOS induction in myocardial tissue (P<0.05). Oleu exerts a protective effect by eliminating DXR induced cardiotoxicity expressed by the alteration of intracellular and peripheral markers. Combined oleu and DXR treatment improves the therapeutic outcome by preventing undesirable toxicity.
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PMID:Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical oleuropein through suppression of oxidative and nitrosative stress. 1722 28

ABSTRACT Sustained high levels of circulating catecholamines may induce cardiotoxicity through oxidative mechanisms. Isoproterenol is a synthetic catecholamine with increasing attention owing to this application in cardiology. The aim of the present study was to investigate the cardioprotective effects of ursolic acid against isoproterenol-induced myocardial ischemia. Normal Wistar strain rats were pretreated with UA (20, 40, and 60 mg/kg, s.c.) for 7 days and then intoxicated with isoproterenol (ISO, 85 mg/kg, s.c. for 2 consecutive days). Hearts were excised from the experimental animals and assessed for the activities of cardiac markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK)], the levels of lipid peroxide products [thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HPs), and conjugated dienes (CDs)], myeloperoxidase (MPO), lipid profiles [total cholesterol (TC), free cholesterol, ester cholesterol, triglycerides (TG), free fatty acids (FFAs), and phospholipids (PLs)], and membrane-bound enzymes (total ATPase, Na(+)K(+)ATPase, Ca(2+)ATPase, and Mg(2+)ATPase). In ISO-treated group, shrinkage of cardiac markers and elevated lipid peroxidation with compromised lipid profiles in the heart where accompanied by the decreased activities of membrane-bound enzymes. The prior administration of UA significantly (p < 0.05) prevented the isoproterenol-induced alterations and restored the enzymes to near normal. These findings indicate the cardioprotective activities of UA during isoproterenol-induced myocardial ischemia.
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PMID:Protective effect of ursolic Acid against myocardial ischemia induced by isoproterenol in rats. 2002 Sep 88

The involvement of catecholamines in stress-induced heart injury is well documented. However, the contribution of adrenergic receptor types is less understood. Both the profile of plasma marker enzyme activities (lactate dehydrogenase-1 and aspartate transaminase) and the distribution and morphology of the lesions observed in tissue sections of adrenaline-injected mice resembled those of stressed (restraint and cold exposed) mice. Next, we compared the effect of isoproterenol (beta-adrenergic agonist) and phenylephrine (alpha1-adrenergic agonist) on both heart function and tissue injury. In Langendorff-perfused rat hearts, alpha1-adrenergic receptors made a minor contribution to the tonic effect of adrenaline, as indicated by the lack of effect on the heart rate and the delayed negative inotropic effect of phenylephrine. However, in whole mice, phenylephrine but not isoproterenol, induced an increase of both lactate dehydrogenase-1 and aspartate transaminase activities. Hearts of phenylephrine-injected mice showed necrotic lesions in subendocardial areas of the left ventricle. In addition a scattered focal leukocyte infiltration around single apoptotic-like myocytes was observed in the ventricle wall. Hearts of isoproterenol-injected mice showed a similar number of apoptotic-like myocytes, but a much lower number of necrotic areas, than phenylephrine-injected animals. Our results suggest that the cardiotonic effect of catecholamines involves mainly the beta-adrenergic receptors. However, the acute catecholamine-induced heart injury involves mainly alpha1-adrenergic receptors.
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PMID:Catecholamine-induced heart injury in mice: differential effects of isoproterenol and phenylephrine. 2023 97

The aim of the present study was to investigate whether soybean oligosaccharides (SO) protects heart function against myocardium ischemia reperfusion (MIR) injury. Hearts were 20min global ischemia and 50min reperfusion. Rats were fed for 30days with saline (sham and MIR groups) or the SO (200 or 400mg/kg body weight, daily). At the end of 30days, the left main coronary artery was occluded for 30min, followed by 24h reperfusion, in anesthetized rats. Sham operated animals were subjected to the same surgical procedures, except that the suture under the left anterior descending coronary artery was not tied. Results showed that SO decreased malondialdehyde (MDA) level and increased antioxidant enzymes activities in the SO-treatment group. Pre-treated with SO it showed a significant recovery in cardiac contractile function, reduction in infarct size, and decrease in creatine kinase (CK), aspartate transaminase (AST) and lactate dehydrogenase (LDH) activities. Moreover, SO also significantly increased the expression of p-JAK2 and p-STAT3 proteins in rat heart. However, no significant change in JAK2 and STAT3 levels was observed. Activation of JAK2/STAT3 pathway showed a significant protective role in the SO-treatment group. Perhaps, the altered activation of the JAK2/STAT3 pathway in ischemic myocardium is one mechanism by which SO is cardioprotective.
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PMID:Evaluation of cardio-protective effect of soybean oligosaccharides. 2544 24