Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardioprotective and antiarrhythmic effects of three beta-blockers with different pharmacological properties were investigated in 33 anesthetized dogs with a 2-h coronary occlusion. Dogs were divided into 4 groups and received physiological saline or one of the following drugs using a 10-min infusion at 25 min before the occlusion: saline or control (n = 12), propranolol (0.3 mg/kg, n = 7), bisoprolol (0.05 mg/kg, n = 7), and nipradilol (0.2 mg/kg, n = 7) groups. Blood pressure did not significantly differ among the 4 experimental groups throughout the entire observation period. On the contrary, the postocclusion change (fall) in heart rate from the preocclusion value was significantly (P less than 0.05-0.01) greater in the drug-treated groups than in the control group. Each of the beta-blockers effectively prevented the development of ventricular arrhythmias associated with the 2-h coronary occlusion. In terms of assessing a cardioprotective effect, the respiratory control index and rate of oxygen consumption in State III in mitochondria, and lysosomal enzyme activities (N-acetyl-beta-glucosaminidase or beta-glucuronidase) in myocardial tissues, all prepared from both ischemic and non-ischemic areas, were measured using the respective, established methods. The 2-h coronary occlusion induced a mitochondrial dysfunction and leakage of lysosomal enzymes in the control group, whereas each beta-blocker significantly (P less than 0.05-0.01) protected mitochondria against ischemia and prevented the lysosomal enzyme leakage. The results indicate that the antiarrhythmic effects of beta-blockers on ischemic myocardium are, at least in part, due to their cardioprotective action, and these effects appear to be unrelated to the ancillary pharmacological properties of these drugs.
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PMID:Cardioprotective and antiarrhythmic effects of beta-blockers, propranolol, bisoprolol, and nipradilol in a canine model of regional ischemia. 257 96

This study was designed to clarify the cardioprotective effects of various class I antiarrhythmic drugs, i.e., aprindine, disopyramide, flecainide, lidocaine, mexiletine, pentisomide and propafenone, on the ischemic heart. Sixty-one adult mongrel dogs were classified into eight groups according to premedication: 1) control group, physiologic saline solution was administered intravenously 25 min before left anterior descending coronary artery ligation; 2) aprindine group, 3 mg/kg body weight of aprindine intravenously; 3) disopyramide group, 2 mg/kg of disopyramide intravenously; 4) flecainide group, 2 mg/kg of flecainide intravenously followed by drip infusion of 100 micrograms/kg per min; 5) lidocaine group, 2 mg/kg of lidocaine intravenously followed by drip infusion of 100 micrograms/kg per min; 6) mexiletine group, 3 mg/kg per min of mexiletine intravenously followed by drip infusion of 15 micrograms/kg per min; 7) pentisomide group, 5 mg/kg intravenously; and 8) propafenone group, 2 mg/kg intravenously. Arterial blood pressure and electrocardiogram were monitored throughout the experiment. Two hours after coronary occlusion, the heart was excised. Myocardial mitochondria were prepared and mitochondrial function (the respiratory control index and the rate of oxygen consumption in state III) was measured polarographically. Fractionation of myocardial tissues was performed and the lysosomal enzyme (N-acetyl-beta-glucosaminidase and beta-glucuronidase) activities among fractions were measured. No significant hemodynamic changes were observed compared with the control group except for those in the disopyramide and flecainide groups; that is, decrease in heart rate without changes in blood pressure compared with the control group was observed. All antiarrhythmic drugs effectively prevented the development of ventricular arrhythmias associated with ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardioprotective effects of various class I antiarrhythmic drugs in canine hearts. 273 64

The antiarrhythmic and cardioprotective effects of cibenzoline (4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole) were investigated. Nineteen adult mongrel dogs were divided into 2 groups; in the control group, physiological saline (25 ml) was administered, and 20 min after, the left anterior descending coronary artery (LAD) was occluded for 2 h; in the cibenzoline group, cibenzoline (2 mg/kg), was administered 10 min before 2 h LAD occlusion. Blood pressure and appearance of arrhythmias were monitored throughout the experiment. Two h after occlusion, mitochondria were prepared from both ischemic and non-ischemic areas in each group, and their functions were measured polarographically. Fractionation of myocardial tissue from both ischemic and non-ischemic areas was performed, and activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase and beta-glucuronidase) were measured in each fraction. Administration of cibenzoline significantly reduced the appearance of ventricular arrhythmias in association with ischemia. Cibenzoline did not change significantly blood pressure and heart rate. In the control group, mitochondrial dysfunction and leakage of lysosomal enzymes induced by 2 h occlusion were observed. Administration of cibenzoline maintained significantly mitochondrial function and prevented significantly leakage of lysosomal enzymes. These results indicated that cibenzoline has a cardioprotective as well as an antiarrhythmic effect on ischemic myocardium.
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PMID:The effect of cibenzoline on myocardial damages in dogs. 275 58

A previously validated small mammal trauma model, hind-limb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to investigate the effects of traumatic injury on hepatic glucuronidation activity. As was previously observed with hepatic oxidative drug metabolism, model trauma resulted in a significant decrease in the in vivo glucuronidation of chloramphenicol, with a 23% drop in clearance of this drug. The effect on in vivo pharmacokinetics appeared to result from a complex interaction between trauma's differential influences on conjugating enzyme(s), deconjugating enzyme(s), and hepatic UDP-glucuronic acid levels, as well as the relative physiological importance of these variables. Hepatic UDP-glucuronyltransferase activities towards both p-nitrophenol and chloramphenicol were elevated (44-54%) after model injury when measured in native hepatic microsomes. However, microsomes which had been "activated" by treatment with Triton X-100 showed no significant difference between control and traumatized animals. Serum beta-glucuronidase activities were elevated by 58%, while hepatic beta-glucuronidase rose by about 16%. Nevertheless, in vivo deconjugation showed no significant change. Model trauma also resulted in a 46% decrease in hepatic UDP-glucuronic acid content. Thus, the observed post-traumatic depression of in vivo chloramphenicol glucuronidation could be due either to a diminished availability of a necessary cofactor (UDP-glucuronic acid) or to an alteration in enzyme kinetics or function in vivo.
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PMID:Effects of model traumatic injury on hepatic drug metabolism in the rat. IV. Glucuronidation. 286

The protective effects of PGE1 on ischemia-related liver damage were evaluated in dogs. Ninety minutes warm hepatic ischemia was induced by the total clamping of hepatic inflow vasculatures with portal bypassing. The survival rate improved up to 62.5% when PGE1 was administered intravenously prior to ischemia, while no dog survived for longer than 1 week in the nontreated group. Hepatic ATP content was restored up to 80% of preischemic level 2 h after reflow in the PGE1 pretreated group, compared to 55% recovery in the nontreated group. Complete normalization of hepatic energy charge and rapid decrease of lactate were also seen in the PGE1 group. The clearance rate of intravascular lipid emulsion remained fairly normal in the PGE1 group, thereby suggesting well-preserved hepatic reticuloendothelial functions. The serum activities of beta-glucuronidase, GOT and GPT were suppressed in the PGE1-pretreated group, thereby implying a well-protected hepatic integrity. The histology revealed well-preserved hepatic architecture. The remarkable cytoprotective effect of PGE1 on hepatic ischemia shown in this study indicates that PGE1 warrants further study for protection of ischemically compromised hepatic allografts.
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PMID:Protective effect of prostaglandin E1 (PGE1) on energy metabolism and reticuloendothelial function in the ischemically damaged canine liver. 292 40

Intracellular enzyme activities can be greatly influenced by alterations of pH, and non-physiologic pH may inhibit cell metabolism. The study was undertaken to examine the influence of pH values in preservation solution on ischemic tolerance time of the liver. BDE rat livers were used. Livers were preserved for 20 min or 2 h in warm ischemia after an initial perfusion with Ringer's solution at pH 9.0, 7.4, and 6.0. The values of total adenine nucleotide (TAN) and energy reserve (ER) in the livers were determined at the end of the preservation. After 20 min of warm ischemia, TAN values at pH 9.0 and 7.4 fell to 2.727 +/- 0.255 and 2.410 +/- 0.164 mumol/g, respectively (normal values: 3.414 +/- 0.270 mumol/g) and ER values to 0.786 +/- 0.186 mumol/g at pH 9.0 and to 0.446 +/- 0.095 mumol/g at pH 7.4 (normal values: 2.962 +/- 0.214 mumol/g). A similar trend was also observed after 2 h of warm ischemia. The preservation with a solution at pH 6.0 did not present any difference as compared to that at pH 7.4. Four-hour preservation in cold ischemia with Ringer's solution at pH 9.0 rendered higher values of TAN (2.635 +/- 0.085 mumol/g) and ER (0.336 +/- 0.026 mumol/g) than those in preservation at pH 7.4. No significant difference between TAN and ER values was found when 4-h preservation at pH 7.4 and 6.0 was compared. In another group an intermittent liver perfusion at 1-h interval was performed with chilled Ringer's solution; afterwards GOT, GPT, beta-glucuronidase, and acid phosphatase values in the effluents were evaluated. All of these enzymes showed higher concentration in the effluent with solution at pH 7.4 than that at 9.0. These results suggested that better intracellular energy reserve and organ viability can be maintained by preservation with alkaline solution. Furthermore, ER values seemed to be an excellent indicator of the organ viability during preservation. These were also confirmed by orthotopic hepatic transplantation in pigs. Livers were successfully preserved with alkaline Ringer's solution for up to 12 h. However, without change of pH, livers could not be preserved for more than 4.5 h.
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PMID:[Prolongation of ischemic tolerance time of donor livers by alkaline preservation solutions]. 647 1

This study investigated lysosomal disruption during hypothermic perfusion preservation of kidneys and its possible relationship to viability. The percentage of free and bound enzyme activity was analyzed for three lysosomal enzymes in homogenates made from perfused canine kidney cortex tissue, including beta-glucuronidase, cathepsin-D, and aryl sulfatase. All three enzymes displayed characteristic increases in free enzyme activity (47-68%) throughout 5 days of perfusion preservation. The increased activity obtained at 5 days of preservation was found to indicate "severe" tissue damage, as shown by a similar increase obtained in renal cortex tissue exposed to warm ischemia (37 degrees C) for 4 hr or longer. Aryl sulfatase was found to be the most sensitive indicator of severe damage. Pretreatment of kidney donors with methylprednisolone, a lysosomal stabilizer, was also studied in kidneys exposed to 5 days of perfusion. Pretreatment was found to reduce the percentage of free lysosomal enzyme activity following 5 days (nonviable) of perfusion to those levels normally obtained following 3-day (viable) perfusion. This indicates that methylprednisolone may be useful in modulating the severe disruption of lysosomes induced by long-term preservation. It is concluded that extensive disruption of lysosomes occurs during hypothermic perfusion preservation and may represent one cause for loss of organ viability.
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PMID:Lysosomal enzyme release in hypothermically perfused dog kidneys. 649 98

Cytoprotective effect of 16,16-dimethyl prostaglandin E2 (PGE2) was studied on splanchnic ischemia in rats. The superior mesenteric artery or the vascular pedicle to the isolated right hepatic lobe was occluded for 30 min, respectively, 1 or 2 h. Groups of rats were pretreated with PGE2 in a dose of 5 micrograms/kg b.w. 30 min before induction of ischemia. Ischemic damage was assessed by release of the lysosomal enzyme beta-glucuronidase and ALAT into circulation, the enzyme content in ischemic bowel and histology. Small bowel ischemia induced a marked enzyme release, a decrease of enzyme and protein content in the ischemic mucosa and typical histologic alterations. These findings were abolished in rats pretreated with PGE2. Occlusion of the vascular pedicle of the right hepatic lobe also caused enzyme release and histologic changes, but these were not affected by pretreatment with PGE2. PGE2 has a protective effect on small bowel ischemia and the observations support the concept that PGE2 may act by stabilization of cellular cytomembranes. No effect was observed on ischemic liver cell injury and this type of cell injury may be caused by other disturbances of cell function besides altered membrane function.
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PMID:Cytoprotective effect of 16,16-dimethyl prostaglandin (PGE2) on ischemic splanchnic injuries in the rat. 669 78

Alterations in myocardial acid hydrolases in acute ischemia were studied in relation to the evolution of cardiac cellular necrosis by the determination of cathepsin D, acid phosphatase (AcPase), and beta-glucuronidase activities of the myocardial fractions and by electron microscopic cytochemical studies on AcPase in the canine heart. In the normal myocardium, the same level of activity of acid hydrolases was found in sarcoplasmic reticulum (SR) as in the lysosome fraction. In electron microscopy, AcPase reaction products were observed markedly in SR and moderately in lysosomes, in residual bodies, and in Golgi apparatus. In the ischemic myocardium, at 20 to 30 min after coronary ligation, activation of these enzymes was observed in both SR and lysosomes, and at 60 to 90 min they were decreased in the particles and, in turn, increased in the cytoplasm accompanying the ischemic fine structural changes. At 2 to 3 hr those acid hydrolase activities in the cytosol were decreased, indicating the loss of enzymes from necrotic myocardial cells. Acid hydrolases are the most important factor for the evolution of ischemic myocardial necrosis by being activated not only in lysosomes but also in SR and by being released to the cytoplasm to disintegrate the cellular structures.
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PMID:Acid hydrolases in the initiation of ischemic myocardial necrosis. 685 64

Activities and subcellular distributions of acid hydrolases, cathepsin D, acid phosphatase and beta-glucuronidase in myocardial subfractions were determined serially with reference to the initiation of myocardial necrosis in dog hearts with acute ischemia. The following results were obtained: 1) In the normal myocardium, respectable activities of three enzymes were obtained either in the sarcoplasmic reticulum or in the lysosome-containing fraction. 2) Thirty min after coronary ligation, an increase in the activities was observed in both lysosome and sarcoplasmic reticulum fractions of the ischemic heart muscle. After 60 to 90 min these activities were decreased rapidly in both fractions to about 70% of those of the normal myocardium with an increase in the cytosolic activity. Two to 3 hours after ligation, the reduction in the cytosolic activity was noted, indicating an escape of the enzymes from the necrotic myocardium. The subcellular distribution of these enzymes was further altered in the ischemic heart muscle for 12 to 14 hours reflecting an infiltration of the interstitial cells. These findings suggest that activation and release of acid hydrolases not only in lysosomes but also in the sarcoplasmic reticulum are one of the primary and the earliest factors for the evolution of ischemic myocardial injury which leads to necrosis.
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PMID:Studies on intracardiac acid hydrolases in the ischemic myocardial necrosis. 714 2


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