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)

Niclosamide, a widely used anthelmintic drug in underdeveloped countries, is known to be mutagenic in the Salmonella typhimurium microsomal test system. The urine obtained from mice treated with niclosamide is mutagenic in the TA98 and TA1538 strains. Its effects on mouse-sperm morphology were evaluated in CD1 and (BALB/cJ x DBA/2J) F1 mice after 5 daily oral niclosamide doses of either 60, 80, 100 or 120 mg/kg. A statistically significant increase in abnormal sperm morphology was detected in both CD1 and (BALB/cJ x DBA/2J) F1 mice. No drug-related effects on testis weight nor on sperm count were observed in either genotype. Urine samples obtained from niclosamide-treated F1 mice were assayed with the Salmonella typhimurium strain TA1538 both in the absence and presence of beta-glucuronidase. In the absence of glucuronidase, urine mutagenicity increased with increasing dose and the highest doses were toxic. In the presence of glucuronidase, urine mutagenicity and toxicity also increased. Only at the highest dose (120 mg/kg), however, was there a positive correlation between the urine mutagenic activity and an increase in the number of abnormal sperm. The results of this study suggest that the increase in abnormal sperm depends on the systemic presence of non-conjugated niclosamide metabolites.
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PMID:Sperm shape abnormality and urine mutagenicity in mice treated with niclosamide. 327 17

Activation of digestive zymogens by lysosomal enzymes has been suggested as a triggering event in acute pancreatitis (AP). chloroquine (CQ), a weak base that accumulates in the lysosomes and increases their pH, can inhibit the activity of lysosomal enzymes. In the present study, we examined the effect of CQ on choline-deficient, ethionine-supplemented (CDE) diet-induced AP. CQ-diphosphate (15-50 mg.kg-1) or vehicle was given intraperitoneally at 0, 24, and 48 h to female CD1 mice that were fed with either normal diet or CDE diet. For mortality studies, animals were observed for 168 h. Serum and pancreas samples were collected from animals sacrificed 56 h after the start of the CDE diet. Treatment with CQ at 50 mg.kg-1 significantly (p < 0.05) improved the survival of mice with CDE diet-induced AP. In the normal pancreas, CQ decreased the specific activity of lysosomal enzymes cathepsin B1, beta-hexosaminidase, beta-glucuronidase, and acid phosphatase. In the pancreas with AP, CQ did not modify the activity of cathepsin B1, whereas it increased the latency of all enzymes. In conclusion, our results confirm the beneficial effect of CQ on survival of mice with CDE diet-induced AP and suggest that this effect of CQ may be due to its stabilizing action on lysosomes.
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PMID:Chloroquine stabilizes pancreatic lysosomes and improves survival of mice with diet-induced acute pancreatitis. 978 50