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)

After intravenous administration of (-)-epicatechin gallate to Wistar male rats, its biliary metabolites were examined. Deconjugated forms of (-)-epicatechin gallate metabolites were prepared by beta-glucuronidase/sulfatase treatment and purified by HPLC. Five compounds were subjected to FAB-MS and NMR analyses. These metabolites were shown to be (-)-epicatechin gallate, 3'-O-methyl-(-)-epicatechin gallate, 4'-O-methyl-(-)-epicatechin gallate, 4' '-O-methyl-(-)-epicatechin gallate, and 3',4' '-di-O-methyl-(-)-epicatechin gallate. After oral administration, five major metabolites excreted in rat urine were purified in their deconjugated forms and their chemical structures identified. They were degradation products from (-)-epicatechin gallate, pyrogallol, 5-(3,4-dihydroxyphenyl)-gamma-valerolactone, 4-hydroxy-5-(3,4-dihydroxyphenyl)valeric acid, 3-(3-hydroxyphenyl)propionic acid, and m-coumaric acid. Time course analysis of the identified (-)-epicatechin gallate metabolites showed that (-)-epicatechin gallate and its conjugate appeared in the plasma with their highest levels 0.5 h after oral administration; their levels rapidly decreased, and then they disappeared by 6 h. The degradation products, mainly in their conjugated forms, emerged at 6 h, peaked at 24 h, and disappeared by 48 h. In urine samples, (-)-epicatechin gallate and its methylated metabolites were hardly detected and the degradation products began to be excreted in the 6-24 h period, peaked in the 24-48 h period, and then began to disappear. The most abundant metabolite in both the plasma and the urine was found to be the conjugated form of pyrogallol. On the basis of these results, a possible metabolic route of (-)-epicatechin gallate orally administered to the rat is proposed.
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PMID:Identification of metabolites of (-)-epicatechin gallate and their metabolic fate in the rat. 1292 15

A model experiment was performed on rats to evaluate the effect of partial or total substitution of saccharose (S) and cellulose (C) by preparations of lactulose and inulin on the development and metabolism of the caecum. In the experimental diets given to rats for 4 weeks, the examined preparations were administered either with an equivalent amount of cellulose (each at 4% of the diet) or as sole source of dietary fibre at 8% of the diet. Compared to the saccharose group cellulose had no effect, and low doses of lactulose and inulin in the diet increased to a medium extent the weight of the caecum wall and caecal digesta. The addition of lactulose and inulin at 8% increased significantly the content of caecal digesta (4.62 and 4.11 g/100g BW, respectively) and the weight of the caecal wall (1.10 and 0.86 g/100g BW, respectively), compared to the groups with saccharose and cellulose (0.73, 0.90 and 0.24, 0.28 g/100g BW, respectively). Cellulose and cellulose partially-substituted with lactulose and inulin caused an increase in the dry matter content of caecal digesta (26.5-27.5%), compared to other groups (21.8-22.8%). The administration of lactulose and inulin preparations was accompanied by a significant drop in pH (5.47-5.81), compared to the groups with cellulose or saccharose (6.83-6.91), and a decrease in the ammonia concentration in the caecal digesta, compared to the cellulose control (0.27-0.40 and 0.62 mg/g, respectively). The group with 8% lactulose was characterized by the highest activities of microbiological alpha- and beta-galactosidase and beta-glucosidase in the caecal digesta. Cellulose and both preparations significantly decreased the activity of beta-glucuronidase, compared to the saccharose group (0.39-0.89 and 1.52 U/g, respectively). The highest concentration of VFA in the caecal digesta was observed in the saccharose group (89.2 micromol/g), and the lowest concentration in the group where cellulose was totally substituted by lactulose and inulin (55.1 and 57.5 micromol/g, respectively). The total production of VFA in the caecum was fourfold higher with 8 % lactulose and inulin (254.7 and 236.4 micromol/100g BW, respectively) than in both controls groups (65.1 and 67.8 micromol/100g BW, respectively). The high dose of inulin and lactulose increased the share of propionic acid in the VFA profile (C2:C3:C4) compared to both control groups. When 4% inulin was added to the diet a significant increase of butyrate concentration in the caecum was observed.
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PMID:Physiological effects of lactulose and inulin in the caecum of rats. 1508 67

A major challenge in treating lysosomal storage diseases with enzyme therapy is correcting symptoms in the central nervous system (CNS). This study used a murine model of mucopolysaccharidosis type VII (MPS VII) to test whether pathological and functional CNS defects could be corrected by expressing beta-glucuronidase via bilateral intrastriatal injection of adeno-associated virus type 5 (AAV5betagluc) vectors. After injecting AAV5betagluc, different brain regions expressed active beta-glucuronidase, which corrected lysosomal storage defects. Compared to age-matched littermates, adult MPS VII mice were impaired in spatial learning and memory, as measured by the repeated acquisition and performance chamber (RAPC) assay. AAV5betagluc-treated MPS VII mice improved significantly in the RAPC assay, relative to saline-injected littermates. Moreover, our studies reveal that cognitive changes in MPS VII mice correlate with decreased N-methyl-d-aspartate and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor expression. Importantly, AAV5betagluc delivery restored glutamate receptor levels. Together, these data demonstrate that AAV5 vectors deliver a therapeutically effective beta-glucuronidase gene to the CNS and further suggest a possible mechanism underlying spatial learning defects in MPS VII mice.
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PMID:Adeno-associated virus type 5 reduces learning deficits and restores glutamate receptor subunit levels in MPS VII mice CNS. 1723


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