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)

Human urine is known to contain substances that strongly inhibit bacterial mutagenicity of aromatic and heterocyclic amines in vitro. The biological relevance of these anti-mutagens was examined by comparing levels of tobacco-related DNA adducts in exfoliated urothelial cells from smokers with the anti-mutagenic activity in corresponding 24-h urine samples. An inverse relationship was found between the inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-mutagenicity by urine extracts in vitro and two DNA adduct measurements: the level of the putatively identified N-(deoxyguanosine-8-yl)-4-aminobiphenyl adduct and the total level of all tobacco-smoke-related carcinogen adducts including those probably derived from PhIP. Urinary anti-mutagenicity in vitro appears thus to be a good indicator of the anti-genotoxicity exerted by substances excreted in urine, that protect the bladder mucosal cells (and possibly other cells) against DNA damage. These substances appear to be dietary phenolics and/or their metabolites because (i) the anti-mutagenic activity of urine extracts (n = 18) was linearly related to their content in phenolics; (ii) the concentration ranges of these substances in urine extracts were similar to those of various plant phenols (quercetin, isorhamnetin and naringenin) for which an inhibitory effect on the liver S9-mediated mutagenicity of PhIP was obtained; (iii) treatment of urines with beta-glucuronidase and arylsulfatase enhanced both anti-mutagenicity and the levels of phenolics in urinary extracts; (iv) urinary extracts inhibited noncompetitively the liver S9-mediated mutagenicity of PhIP as did quercetin, used as a model phenolics. Several structural features of the flavonoids were identified as necessary for the inhibition of PhIP and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxiline mutagenicity. Fractionation by reverse-phase HPLC and subsequent analysis of two urinary extracts, showed the presence of several anti-mutagenic substances and phenolics; more lipophilic phenolics displayed the highest specific inhibitory activity. This suggests that enzymatic conversion of dietary flavonoids into their more lipophilic and anti-mutagenic O-methylcatechol derivatives, as noted for quercetin, may occur in vivo in man. Onion, lettuce, apples and red wine are important sources of dietary flavonoids which are probably responsible for the anti-mutagenicity associated with foods and beverages. After HPLC fractionation of urinary extracts, the distribution profile of anti-mutagenic activity corresponded roughly to that of onion and wine extract combined. Our study strongly suggests that smokers ingesting dietary phenolics, probably flavonoids, are partially protected against the harmful effects by tobacco carcinogens within their bladder mucosal cells. This protective effect of dietary phenolics against the cancer of the bladder (and possibly other sites) should be verified and explored as a part of a chemoprevention strategy.
Carcinogenesis 1996 Oct
PMID:Dietary phenolics as anti-mutagens and inhibitors of tobacco-related DNA adduction in the urothelium of smokers. 889 88

We report here that rats possess a hitherto unrecognized xenobiotic-inducible hepatic 7,8-dihydro-7,8-diol-benzo[a]pyrene (BPD) UDP-glucuronosyltransferase (UGT) activity. BPD UGT activity is induced in female F344 rat liver by treatment with the selective Phase 2 conjugation enzyme inducer oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione at 75-450 mg/kg per day for 3 days] and also by a polycyclic aromatic hydrocarbon-type inducer, beta-naphthoflavone (80 mg/kg per day for 3 days). Incubations of oltipraz-treated rat liver microsomes with racemic trans BPD (100 microM) resulted in formation of two fluorescent glucuronides that were resolved by silica thin layer chromatography (Rf 0.5 and 0.6). Incubations with either the (-) or (+) trans BPD isomers resulted in selective formation of the Rf 0.5 [designated -DS, for (-) diol specific] or Rf 0.6 [designated +DS, for (+) diol specific] glucuronide, respectively. The -DS and +DS BPD glucuronides were fluorescent under long wave ultraviolet irradiation, dependent on the presence of UDP-glucuronic acid in the incubation, and were beta-glucuronidase-sensitive. The inducing effect of oltipraz on BPD UGT activity was dose-dependent. The mean BPD UGT activity of the vehicle-treated control group was 0.05 +/- 0.02 nmol/mg per min compared with 0.53 +/- 0.07 nmol/mg per min in the group treated with oltipraz (450 mg/kg per day for 3 days) (P < 0.001). The apparent Km of the induced BPD UGT for BPD was 20 microM, suggesting that the enzyme has the capacity to bind and turnover BPD under physiological conditions. Pretreatment with beta-naphthoflavone, but not phenobarbital, induced BPD UGT activity to approximately the same extent as oltipraz. Neither oltipraz nor beta-naphthoflavone exhibited induction of BPD UGT in livers of homozygous Gunn rats, which lack functional UGT1-encoded isozymes. We conclude that the oltipraz- and polycyclic hydrocarbonresponsive BPD UGT is a member of the UGT1 family. The role of this isoform as a modifier of susceptibility to carcinogenesis elicited by B[a]P remains to be determined.
Carcinogenesis 1997 Jan
PMID:Induction of a rat liver benzo[a]pyrene-trans-7,8-dihydrodiol glucuronidating activity by oltipraz and beta-naphthoflavone. 905 96

Pectin is a partially methoxylated polymer of galacturonic acid obtained from fruits. Among pectin, apple pectin exerts stronger bacteriostatical action on Staphylococcus aureus, Streptococcus faecalis, Pseudomonas aeruginosa and Escherichia coli in comparison with citrus pectin. In this study, we used water-soluble methoxylated pectin from apple. The diet, supplemented by 20% apple pectin, significantly decreased the number of tumors and the incidence of colon tumor. PGE2 level in distal colonic mucosa in 20% apple pectin fed rats were lower than those in basal diet fed rats. Fecal beta-glucuronidase activities in the apple pectin fed group, which has been considered a key enzyme for the final activation of Dimethylhydrazine metabolism to carcinogens in the colonic lumen, were signifieantly lower than those in control group at initiation stage of carcinogenesis. In the case the concentrations of beta-glueosidase and azoreductase were also decreased. The effect of apple pectin on the colon carcinogenesis may partially depend on PGE, concentration decrease in colonic mucosa and on the type of pectin, also related to fecal enzyme activities.
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PMID:Anticarcinogenic action of apple pectin on fecal enzyme activities and mucosal or portal prostaglandin E2 levels in experimental rat colon carcinogenesis. 914 58

The 80%-ethanol extract of lemon grass (Cymbopogon citratus Stapf), a medicinal plant in Thailand, has been reported to be antimutagenic against various known mutagens in the Salmonella mutation assay. To investigate chemoprevention in an animal carcinogenesis model, we examined inhibitory effects of the lemon grass extract on the formation of azoxymethane (AOM)-induced DNA adducts and aberrant crypt foci (ACF) in the rat colon. One week after the start of the treatment with lemon grass extract at doses of 0.5 or 5 g/kg body wt by gavage, F344 rats received two s.c. injections of 15 mg of AOM per kg body weight at 1 week apart. For DNA adduct analysis of the colon and liver, the rats were killed 12 h after the second AOM injection. The DNA from the liver and colon were used for O6-methylguanine and N7-methylguanine analysis. For ACF analysis in the initiation stage, AOM-injected rats were continuously treated with lemon grass extract and were killed 3 weeks after the second AOM injection. For analysis in the promotion stage the treatment with the lemon grass extract (0.5 g/kg) started 2 weeks after the second AOM injection and continued for 12 weeks until the animals were killed. Lemon grass treatment significantly inhibited DNA adduct formation in both the colonic mucosa and the muscular layer but not in the liver. In addition, lemon grass extract treatment significantly inhibited ACF formation in both the initiation stage and the promotion stage. Especially in the promotion stage, lemon grass treatment inhibited the formation of larger ACF (with four or more crypts per focus), which was predictive of tumor incidence. Furthermore, lemon grass extract inhibited fecal beta-glucuronidase competitively and had antioxidant activity. These results suggest that the lemon grass extract inhibits the release of activated aglycon, methylazoxymethanol, from a glucuronide conjugate in the colon, and decreases the DNA adducts and ACF formation in the rat colon.
Carcinogenesis 1997 May
PMID:Inhibitory effects of lemon grass (Cymbopogon citratus Stapf) on formation of azoxymethane-induced DNA adducts and aberrant crypt foci in the rat colon. 916 80

The effect of Bifidobacterium longum (4 x 10(8) viable cells/g diet) and a derivative of inulin ('Raftiline HP'; 5% w/w in diet) on colonic aberrant crypt foci (ACF) induced by the colon carcinogen azoxymethane (AOM) has been studied. The concentration of ammonia, a putative tumour promoter produced by bacterial degradation of protein and urea, and the activities of certain bacterial enzymes thought to play a role in colon carcinogenesis, beta-glucuronidase and beta-glucosidase were also assayed. Consumption of either B. longum or inulin was associated with a decrease (26 and 41%, respectively) in AOM-induced small ACF (i.e. those comprising 1-3 aberrant crypts per focus). Combined administration of the bifidobacterium and inulin resulted in more potent inhibition of ACF than administration of the two separately, achieving 80% inhibition of small ACF. Furthermore, the combined administration significantly decreased the incidence (by 59%) of large ACF (>4 aberrant crypts per focus), which are considered to be predictive of eventual tumour incidence. Since the dietary treatments were started 1 week after the carcinogen dose, the results suggest that B. longum and inulin may be affecting the early promotion phase of the carcinogenic process. Consumption of diets containing B. longum, inulin or both were also associated with decreases in beta-glucuronidase activity and ammonia concentration in the caecal contents. Both these factors have been associated with carcinogenesis of the colon in experimental animal models. In rats given inulin-containing diets (with or without B. longum) an increase in caecal wt and beta-glucosidase activity and a decrease in caecal pH were observed. The results suggest that consumption of B. longum or inulin was associated with potentially beneficial changes in caecal physiology and bacterial metabolic activity in relation to tumour risk and in the incidence of putative preneoplastic lesions in the colon. The results also indicated that combined treatment with the two agents was more effective in reducing colonic lesions.
Carcinogenesis 1998 Feb
PMID:Effect of Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced aberrant crypt foci in rats. 949 77

Experiments involving the use of 1,2-dimethylhydrazine-induced colonic tumors in rats showed long-term treatment with a newly synthesized drug EDE-10g to inhibit an enzyme of enteric beta-glucuronidase, to suppress carcinogenesis and to prolong lifespan of animals.
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PMID:[New means for the prophylaxis of colon cancer with the use of beta-glucuronidase inhibitors]. 957 35

The ingestion of viable bacteria is thought to be required to modify intestinal microflora. In the present study, the effects on fecal flora of consumption of cell-free concentrated whey from milk that had been fermented with Bifidobacterium breve C50 was tested using 10 healthy human volunteers. Results were compared with effects of a commercial milk formula that had been fermented with Streptococcus thermophilus and B. breve C50 and given to 10 control subjects. Nitroreductase and beta-glucuronidase activities were assessed as risk indexes for colon carcinogenesis, and beta-galactosidase was measured as an indicator of the fermentation capacity of the colonic flora. Fecal excretion of Bacteroides fragilis, Clostridium perfringens, and clostridial spores decreased after 7 d of consumption of either preparation; however, counts of bifidobacteria only increased after intake of B. breve whey. Fecal pH was reduced from 7.1 +/- 0.2 to 6.6 +/- 0.3 after intake of whey that had been fermented with Bif. breve. Fecal nitroreductase and beta-glucuronidase significantly decreased, and beta-galactosidase activity increased, after consumption of either preparation. The results indicate that ingestion of viable bifidobacteria was not required to modify intestinal flora of humans. Repression of B. fragilis and clostridia seems to be independent of colonic bifidobacterial overgrowth in humans.
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PMID:Cell-free whey from milk fermented with Bifidobacterium breve C50 used to modify the colonic microflora of healthy subjects. 962 Dec 24

The influence of bovine lactoferrin (bLf) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). In experiment I, 2% and 0.2% bLf, and Bifidobacterium longum (B. longum) as a positive control at 3% were given in the diet for 4 weeks, along with two s.c. 15 mg/kg injections of AOM on days 1 and 8. The numbers of aberrant crypt foci (ACF) were decreased by both treatments. Similar results were obtained in experiment II of 13 weeks duration. In experiment III, animals were given three weekly injections of AOM and then received 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bovine lactoferricin (bLfcin) for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with almost all the treatments. Thus, the incidences of colon adenocarcinomas in the groups receiving 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bLfcin were 15%, 25%, 26.3% and only 10%, respectively, in contrast to the 57.5% control value (p < 0.01). ACF values also exhibited reduced development. Investigation of beta-glucuronidase revealed decrease in the cecal contents of animals receiving bLf. In addition, demonstration of enhancement of NK activity by bLf indicated that its inhibitory effects could have been related to elevated immune cytotoxicity.
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PMID:Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci development by bovine lactoferrin administration in F344 rats. 978 70

The present experiments were aimed at developing novel dietary fibers to aid in reduction of colon cancer risk. We assessed the effects of coffee (non-fiber fraction), coffee fiber (arabino-galactose polymer) and inulin (oligo-fructose) in male F344 rats using formation of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in the colon as the measure of preventive efficacy (or lack of such). At 5 weeks of age, groups of rats were fed the AIN-76A (control) and experimental diets that contained 1% coffee, 10% coffee fiber, 10% inulin, 10% pectin (positive control for fiber) or 200 p.p.m. piroxicam (a known ACF inhibitor). At 7 weeks of age, all animals were s.c injected with AOM (15 mg/kg body wt) once weekly for 2 weeks. All rats were killed 8 weeks after the last AOM injection and ACF were counted. The contents of the cecum were analyzed for bacterial beta-glucuronidase activity and short-chain fatty acids (SCFAs). Dietary administration of coffee fiber significantly suppressed AOM-induction of colonic ACF, in terms of total number, as well as crypt multiplicity and number of ACF/cm2 colon (P < 0.01-0.001). Inulin diet had no significant effect on total ACF, but had reduced the number of ACF/cm2 (P < 0.05). Whereas coffee had no effect on ACF formation, 10% pectin diet and 200 p.p.m. piroxicam significantly suppressed colonic ACF (P < 0.001) as had been expected. A significant reduction of cecal beta-glucuronidase activity was observed in the rats fed coffee, coffee fiber and pectin diets. Further, coffee fiber, inulin and pectin increased cecal SCFA levels 3- to 5-fold. These results suggest that coffee fiber can prevent colon cancer risk. Further studies are warranted to determine the full potential of this fiber in pre-clinical efficacy studies.
Carcinogenesis 1998 Oct
PMID:Prevention of colonic aberrant crypt foci and modulation of large bowel microbial activity by dietary coffee fiber, inulin and pectin. 980 64

The modifying effects of auraptene isolated from the peel of citrus fruit (Citrus natsudaidai Hayata) on macrophage and lymphocyte functions were investigated in mice. Female BALB/c mice were gavaged with auraptene at a dose of 100, 200 or 400 mg/kg once a day for 10 consecutive days. Glucose consumption of peritoneal macrophages was significantly higher than that in the control group (P < 0.05-0.001) in auraptene-treated mice at all doses at 24, 48 and 72 h incubation except for mice given 200 mg/kg auraptene at 24 h incubation. Activity of acid phosphatase in peritoneal macrophages was significantly increased in mice treated with auraptene at a dose level of 100 mg/kg (P < 0.001). Activity of beta-glucuronidase in peritoneal macrophages in the auraptene-treated mice at all doses was significantly higher than that in the control group (P < 0.001), but there was no significant difference in lactate dehydrogenase activity of peritoneal macrophages at any dose. Interleukin (IL)-1beta production of peritoneal macrophages in the auraptene-treated mice at all doses was significantly higher than that in the control group (P < 0.05-0.001). Tumor necrosis factor alpha production of peritoneal macrophages in mice gavaged with auraptene at a dose of 200 mg/kg was significantly higher than that in the control group (P < 0.05). Auraptene did not affect proliferation of spontaneous splenic lymphocytes in mice at any dose. Stimulation indices in mice given auraptene at a dose of 200 mg/kg were significantly higher than that in the control group (P < 0.05). When spleenic lymphocytes were cultured without concanavalin A (Con A), IL-2 and interferon (IFN) gamma productions were not detectable in the supernatant. However, IL-2 and IFN production stimulated by Con A were significantly increased in mice gavaged with auraptene at dose levels of 100 and 200 mg/kg (P 0.05-0.001). Auraptene did not enhance spontaneous IL-4 production by splenocytes. There was no significant difference in IL-4 production of splenic lymphocytes stimulated by Con A in all groups. These findings might suggest that oral administration of citrus auraptene effectively enhanced macrophage and lymphocyte functions in mice.
Carcinogenesis 1999 Aug
PMID:Immunomodulatory action of citrus auraptene on macrophage functions and cytokine production of lymphocytes in female BALB/c mice. 1042 94


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