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)

Endotoxin plays an important role in the pathogenesis of septicaemia by activation of cellular and plasmatic systems. This study was performed to investigate the effects of infusion of endotoxin in rabbits by measuring the activation of cellular and plasma systems. Endotoxin was infused at a rate of 1 mg/kg body wt for 10 min, which caused death of all rabbits within 72 h. Endotoxin induced early leukopenia and thrombopenia, increased plasma levels of beta-glucuronidase and leukotriene B4 (LTB4), and decreased complement total hemolytic activity (CH50) and tissue plasminogen activator (t-PA) activity. These observations correlate with the cellular and plasma changes that have been documented in severely ill endotoxemic patients. Therefore, we conclude that this endotoxin model in rabbits is a valuable tool for investigation of pathophysiology and treatment of endotoxic shock.
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PMID:Activation of plasma systems and blood cells by endotoxin in rabbits. 164 34

Endotoxemia in patients can lead to sepsis and shock by activation of cellular and plasmatic systems. Corticosteroids are described to have a beneficial effect on these phenomena. In this study of controlled endotoxic shock, we investigated the protective effects of prophylactic corticosteroid treatment against activation of cellular and plasmatic systems. In this respect, a low-dose methylprednisolone (1 mg/kg body wt) treatment was compared with that of a high-dose methylprednisolone (40 mg/kg body wt) treatment. Endotoxin infusion induced death of all rabbits, which was associated with leukopenia, thrombopenia, increased levels of beta-glucuronidase, and leukotriene B4 (LTB4) and decreased levels of complement total hemolytic activity (CH50) and tissue plasminogen activator (t-PA) activity. Both methylprednisolone regimens prevented death of the rabbits after endotoxin infusion, which correlated with a significant decrease of the granulocyte release product beta-glucuronidase (P less than 0.01). The early leukopenia and thrombopenia were not prevented; however, both cell numbers returned more rapidly to baseline values than in the placebo group (P less than 0.01, P less than 0.05). The LTB4 and CH50 concentration and t-PA activity did not differ significantly between the treated and placebo groups. These results indicate that although methylprednisolone has no inhibitory effect on the activation of the complement, arachidonic acid, and fibrinolytic systems, it protected the animals from the deleterious effects of endotoxin shock by inhibition of leukocyte activation. In this regard a low dosage of methylprednisolone is equally effective as the most often recommended high dose.
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PMID:Methylprednisolone prophylaxis protects against endotoxin-induced death in rabbits. 164 35

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

Dietary glutamine has been suggested to preserve structural and functional integrity of the gut and high dose bolus glutamine has been hypothesized to protect against potentially fatal endotoxic shock, hyperthermic stress, and side effects of chemotherapy. In this study, we aimed to relate the ability of high dose oral bolus glutamine to mitigate the severe diarrhea induced by 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) chemotherapy to specific cytoprotective mechanisms [heat shock response, glutathione (GSH)] in gut and tumor tissues. Female rats bearing Ward colon tumor received CPT-11 (125 mg x kg(-1) x d(-1)x 3 d) with or without an oral glutamine bolus (0.75 g/kg) administered 30 min prior to each CPT-11 dose. Glutamine reduced incidence and severity of late-onset diarrhea following CPT-11 treatment (P < 0.05) and was associated with potentially beneficial and protective responses in the colon: 1) a 3.1- to 7.2-fold increase of heat shock protein (Hsp)25,-70, and -90alpha (P < 0.05); 2) increased reduced GSH (rGSH):oxidized GSH ratio (P < 0.05); 3) prevention of upregulated activity of a key bacterial enzyme (beta-glucuronidase) in the cecal content that mediates CPT-11 intestinal toxicity (P < 0.05); and 4) increased proportions of CD3+CD8+ lymphocytes and memory CD8+ subset in mesenteric lymph nodes following CPT-11 therapy. By contrast, glutamine treatment did not alter CPT-11's antitumor activity, the amino acid concentrations, Hsp expression, or the ratio of rGSH:oxidized GSH in the tumor. Our data demonstrate a striking dichotomy in the response of tumor and host to oral glutamine administration, concurring with the concept that this nutrient may favorably alter the balance between the host and tumor.
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PMID:Bolus oral glutamine protects rats against CPT-11-induced diarrhea and differentially activates cytoprotective mechanisms in host intestine but not tumor. 1835 29