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)

Prostaglandins participate in the pathophysiology of endotoxin shock; however, their exact role has not yet been clear. In this study, we investigated the role of the proaggregatory vasoconstrictor, thromboxane A2 (TXA2), an arachidonic acid metabolite, during canine endotoxin shock. The central venous plasma levels of thromboxane B2 (TXB2), the stable metabolite of TXA2, was measured by radioimmunoassay. We also investigated the therapeutic effect of reduced glutathione (GSH), a potential cell-stabilizing sulfhydryl compound, in canine endotoxin shock. Sixty minutes after the intravenous administration of E. coli endotoxin (1 mg/kg), the plasma TXB2 levels were significantly increased from 68.8 +/- 49.0 pg/ml to 318.3 +/- 117.2 pg/ml (N = 5) in the control group and from 67.9 +/- 68,4 pg/ml to 222.6 +/- 133.2 pg/ml (N = 5) in the GSH (300 mg/kg/hr) group. The levels in the GSH group were somewhat lower than in the control group for 60 to 180 minutes after the injection of endotoxin. Thromboxane A2 value appear not to relate to early thrombocytopenia and pulmonary hypertension but to relate to the change of late coagulopathy and of pulmonary vascular resistance. The administration of GSH suppressed the lactic acidemia significantly, however there was a much more decrease in the mean arterial pressure in the GSH group than in the control group. In addition, there was a tendency to inhibit the increase of the serum beta-glucuronidase activity in the GSH group.
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PMID:Thromboxane A2 and hemodynamic-biochemical parameters in canine endotoxin shock. 658 Sep 66

Endotoxic shock is associated with increased metabolism of arachidonic acid to thromboxanes (TX) and prostaglandins (PG). This study assessed the effects of varied doses of aspirin, an inhibitor of arachidonic acid metabolism, on Salmonella enteriditis endotoxin (20 mg/kg)-induced mortality, plasma levels of arachidonate metabolites and other pathophysiological sequelae in Long-Evans rats. Aspirin, in doses of 3.75, 15 an 30 mg/kg, given 30 min before endotoxin significantly (P less than .01) improved 24-hr survival from 11% to 60 to 70%, but 100 mg/kg afforded no protection. Pretreatment with aspirin (15 or 100 mg/kg) 30 min before endotoxin significantly (P less than .001) decreased the endotoxin-induced elevations in plasma levels of immunoreactive (i) TXB2, a stable metabolite of TXA2, i6-keto PGF1 alpha, a stable metabolite of PGI2 and significantly (P less than .05) inhibited thrombin-induced in vitro platelet iTXB2 synthesis. Endotoxin-induced hypoglycemia and elevations in serum acid phosphatase and beta-glucuronidase activities, lysosomal enzymes, were all significantly (P less than .01) attenuated by pretreatment with aspirin (15 mg/kg) 30 min before endotoxin. Aspirin (15 or 100 mg/kg) given 24 h before challenge with endotoxin significantly improved 24-hr survival to 42 (P less than .01) and 44% (P less than .005), respectively. Although 24 hr pretreatment with aspirin (15 or 100 mg/kg) significantly (P less than .001) reduced endotoxin-induced elevations in iTXB2, only the 100 mg/kg dose significantly lowered plasma levels of i6-keto PGF1 alpha. These observations are consistent with the notion that the beneficial effects of aspirin seen in experimental endotoxic shock may be mediated, in part, via reduction of platelet TXA2 synthesis.
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PMID:Protective effects of aspirin in endotoxic shock. 689 70

The effects of (Z)-11-[(3-dimethylamino)propylidene]-6,11-dihydrodibenz [b.e.]oxepin-2-acetic acid monohydrochloride (KW-4679), an orally active antiallergic drug, on the production of platelet-activating factor (PAF), leukotriene (LT) and thromboxane (TX) induced by Ca2+ ionophore A23187 were examined. KW-4679 at 10 microM reduced the amount of cell-associated PAF by 52.8% in human polymorphonuclear leukocytes (PMNs). KW-4679 (1-100 microM) also inhibited the release of both LTB4 and TXB2, a stable metabolite of TXA2, by human PMNs in a concentration-dependent manner, but did not influence the release of beta-glucuronidase. The 50% inhibitory concentration (IC50) values for LTB4 and TXB2 release were 5.9 and 6.0 microM, respectively. In guinea pig eosinophils, KW-4679 inhibited the release of peptide LTs at a concentration higher than 10 microM (IC50 = 66.9 microM). KW-4679 failed to inhibit PAF acetyltransferase, 5-lipoxygenase and TX synthase, but inhibited the arachidonic acid release by human PMNs in a concentration-dependent manner in a similar concentration as that inhibiting production or release of lipid mediators (IC50 = 19.5 microM). These results indicate that KW-4679 suppresses LTs and TX release and PAF formation by reducing arachidonic acid release from phospholipids, probably through interference with phospholipase A2. The inhibitory action of KW-4679 on PAF, LT and TX production is a beneficial effect of an antiallergic drug.
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PMID:KW-4679, an antiallergic drug, inhibits the production of inflammatory lipids in human polymorphonuclear leukocytes and guinea pig eosinophils. 864 79