Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Medical records of 11 cats with lymphoma involving large granular lymphocytes were reviewed. All 9 cats tested were FeLV-negative. Ten cats had a history of anorexia, lethargy, vomiting, or diarrhea, and had lymphoma involving abdominal viscera. The most common site of tumor in these cats was the jejunum. One cat had cutaneous masses caused by dermal and epidermal infiltration with neoplastic large granular lymphocytes. The most common hematologic abnormality was leukocytosis, characterized by neutrophilia with a left shift (7 cats); 2 cats had a left shift without neutrophilia. None of the cats had lymphocytosis, but immature large granular lymphocytes were found in the blood of 4 cats. The most common serum biochemical abnormalities were hypoalbuminemia (10 cats), hypocalcemia (10 cats), hypoproteinemia (9 cats), high aspartate transaminase activity (9 cats), and hyperbilirubinemia (8 cats). Large granular lymphocytes were characterized by abundant cytoplasm containing distinct azurophilic granules that varied in size and number. The most common cytochemical staining pattern included detection of alpha-naphthyl butyrate esterase, acid phosphatase, and beta-glucuronidase activities. On examination of histologic sections, granules stained weakly eosinophilic with Giemsa and moderately with periodic acid-Schiff reaction. Ultrastructurally, the granules appeared membrane bound and contained an electron-dense matrix in 4 cats.
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PMID:Lymphoma involving large granular lymphocytes in cats: 11 cases (1982-1991). 142 72

In clinical use, irinotecan hydrochloride (CPT-11; 7-ethyl-10-[4-(piperidino)-1-piperidino]carbonyloxycamptothecin), a novel antitumor agent, causes a relatively high incidence of severe forms of diarrhea. We investigated whether baicalin, an inhibitor of beta-glucuronidase, which deconjugates the glucuronide of the active metabolite of CPT-11, SN-38 (7-ethyl-10-hydorxycamptothecin), and Japanese herbal medicines (Kampo medicines) which contain baicalin can ameliorate CPT-11-induced intestinal toxicity in rats. CPT-11 (60 mg/kg i.v. once daily for 4 consecutive days) induced intestinal toxicity characterized by diarrhea, loss of body weight, anorexia and disruption of intestinal epithelium. Treatment with baicalin (25 mg/kg p.o. twice daily) or Kampo medicines (TJ-14 and TJ-114; 1 g/kg p.o. twice daily) from the day before to 4 or 10 days after the start of CPT-11 administration resulted in significantly decreased weight loss, improved anorexia and delayed onset of diarrheal symptoms. Histological examination revealed that Kampo medicine-treated animals had less damage to the intestinal epithelium and that damage was repaired more rapidly than in control rats. These results suggest that the prophylactic use of Kampo medicines (TJ-14 and TJ-114) may be of value against CPT-11-induced intestinal toxicity.
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PMID:Protective effects of kampo medicines and baicalin against intestinal toxicity of a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats. 749 18

Irinotecan hydrochloride (CPT-11), an antitumor camptothecin derivative, causes severe forms of diarrhea clinically. We characterized CPT-11-induced diarrhea histologically and enzymologically and assessed the relationships between intestinal toxicity and the activity of the enzymes that play a key role in the major metabolic pathway of CPT-11 in rats. CPT-11 (60 mg/kg i.v. for 4 days) induced intestinal toxicity characterized by severe chronic diarrhea, loss of body weight, and anorexia. Histological damage was most severe in the cecum. The segmental difference in the degree of the damage showed good correlation with the beta-glucuronidase activity in the contents of the lumen in each case, but not with the intestinal tissue carboxylesterase activity, which converts CPT-11 to its active form (7-ethyl-10-hydroxycamptothecin). Inhibition of the beta-glucuronidase activity in the intestinal microflora by antibiotics (1 mg penicillin and 2 mg streptomycin per ml of drinking water) markedly ameliorated the diarrhea and reduced cecal damage. Analysis of CPT-11 and its metabolites in the feces indicated that antibiotics completely inhibited the deconjugation of the glucuronic conjugate of 7-ethyl-10-hydroxycamptothecin by beta-glucuronidase. It is suggested that CPT-11-induced diarrhea would be attributable to the damage to the cecum, and that the inhibition of the beta-glucuronidase activity in the intestinal microflora is a major protective effect of antibiotics.
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PMID:Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats. 870 20