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At least 1,063 records · Page 59Linked to original sources
PubMed1997

Bile acid metabolism in young-old parabiotic rats.

Serum cholesterol, triglyceride and phospholipid levels, liver cholesterol concentration, bile flow, biliary cholesterol, phospholipid and bile acid secretion rates, fecal sterol and bile acid levels and their bile acid compositions were examined in young-old parabiotic rats and compared with those in young and old control rats and young-young parabiotic rats. Bile acid composition was expressed in terms of the cholic acid group/chenodeoxycholic acid group (CA/CDCA) ratio. Body weight (BW) gain decreased after parabiosis especially in old rats, but the liver weight (g/100 g BW), diet-intake, feces dry weight, liver cholesterol concentration and fecal sterol level were almost the same in all the groups. The biliary bile acid secretion rate was higher and the fecal bile acid level was lower in old rats than those in young rats but both the levels became comparable with those in young rats after parabiosis of old rats with young rats. Young rats, however, showed no changes in these levels after parabiosis. The serum cholesterol level and the biliary and fecal CA/CDCA ratios in old rats were higher than those in young rats but decreased after parabiosis with young rats, although they were still higher than those in young rats. The serum cholesterol level in young rats increased after parabiosis with old rats, but not after parabiosis with young rats, and the fecal bile acid level and the CA/CDCA ratio were not changed in either case. It is concluded from these findings that the serum cholesterol level and the CA/CDCA ratio increased with age and that these increases were prevented after parabiosis with young rats while young rats, although their serum cholesterol level was increased, showed no increase in the CA/CDCA ratio after parabiosis with old rats.

Aging↗
PubMedDate not supplied

The mutagenicity of bile acids using a fluctuation test.

The mutagenicity of bile acids was detected by a fluctuation test using Salmonella typhimurium TA100 and TA98 as tester strains. Cholic acid, chenodeoxycholic acid, deoxycholic acid and ursodeoxycholic acid were mutagenic in this test while lithocholic acid was not. The mutagenicity of the bile acids on a molar basis was roughly one-fourth that of methyl methanesulfonate, a moderately potent mutagen. Epidemiological studies have shown a high correlation between levels of bile acids excreted and colon cancer. However, no evidence has previously been reported showing that bile acids are mutagenic. Our results suggest that bile acids may be important in the etiology of colon cancer.

Bile Acids and Salts↗
PubMed1998

Relevance of serum bile acid profile in the diagnosis of intrahepatic cholestasis of pregnancy in an high incidence area: Portugal.

OBJECTIVE(S): The present work was conducted to clarify the relevance of usual liver function tests, and define the most predictive serum bile acid profile for diagnosis of intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: This study comprised 20 healthy nonpregnant women and 77 pregnant women in the last trimester of pregnancy, from which 38 were normal pregnancies, and 39 suffered from ICP. Liver function tests were evaluated by routine laboratory techniques, conjugated bile acids were analysed by high-performance liquid chromatography, and unconjugated forms were measured by an enzymatic-fluorimetric assay. RESULTS: During the third trimester in normal pregnancy, increased concentration of conjugated species affected all primary bile acids, although only significantly for glycocholic acid. Moreover, deoxycholic acid proportion decreased when compared with healthy nonpregnant women. Important ICP-induced changes in serum profiles of amidated bile acids were observed, involving both a marked increase in cholic acid concentration and a shift towards a higher proportion of taurine-conjugated species. Among routine liver tests, alanine aminotransferase and conjugated bilirubin were the most common indicators of ICP. CONCLUSION(S): In the early diagnosis and follow-up of ICP, the most predictive and accurate markers (efficiency 100%) were: (i) TBA concentration in serum >11.0 micromol(-1): (ii) cholic/chenodeoxycholic acid ratio >1.5 and cholic acid percentage >42%: (iii) glycine/taurine bile acid ratio <1.0 or glycocholic acid concentration >2.0 micromol(-1). Accurate diagnosis based on sensitive biochemical markers followed by appropriate treatment may improve both pregnancy outcome and newborn prognosis.

Adolescent↗
PubMed1986

Ursodeoxycholic acid treatment in humans: effects on plasma and biliary lipid metabolism with special reference to very low density lipoprotein triglyceride and bile acid kinetics.

Ursodeoxycholic acid reduces biliary saturation with cholesterol and may induce dissolution of cholesterol gallstones in man. In order to characterize the effects of this potentially useful bile acid on plasma lipid metabolism, we determined lipoprotein levels and very low density lipoprotein (VLDL) triglyceride kinetics in six hypertriglyceridaemic and three normolipidaemic subjects before and after 4-6 weeks of ursodeoxycholic acid treatment at a daily dose of 15 mg kg-1 body weight. The plasma levels of low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol were not significantly affected by therapy. Nor were the plasma level and apparent formation of VLDL triglycerides changed. In five subjects, the effects of a low dose (7.5 mg kg-1 body weight day-1 for 4-6 weeks) of ursodeoxycholic acid on biliary lipid composition and kinetics of cholic acid and chenodeoxycholic acid were determined. The relative concentration of cholesterol in bile was reduced to the same level as during treatment with a high dose of ursodeoxycholic acid. The synthesis rates of bile acids were not suppressed with ursodeoxycholic acid. It is concluded that, unlike chenodeoxycholic acid, ursodeoxycholic acid does not suppress endogenous bile acid production. The efficiency at lower doses, and the lack of effects on plasma lipid metabolism, may make ursodeoxycholic acid a more attractive alternative for clinical attempts of gallstone dissolution.

Adult↗
PubMed1992

Long-term double-blind study on the influence of dietary fibres on faecal bile acid excretion in juvenile ulcerative colitis.

A double-blind cross-over long-term trial (18 months) with randomized supplementation with wheat fibre or ispaghula for two periods of six months, separated by a six-month wash-out period with placebo, was performed in ten patients with juvenile ulcerative colitis to study the effect on faecal bile acid (BA) excretion. All patients were in remission since 0.5-2 years and orally treated with sulphasalazine. The average intake of either fibres was 16 g day-1. Faecal samples were collected (72 h) before and after each fibre period. Faecal water were prepared by centrifugation of faeces at 15,000 g for 2 h. BA in faeces and faecal water were studied using capillary column gas-liquid chromatography-mass spectrometry. Faecal excretion of total BA were not significantly changed by the two fibres. Supplementation with wheat fibre, but not with ispaghula, decreased the faecal concentration of total BA by 43% (p < 0.05), unconjugated BA by 41% (p < 0.01), and taurine conjugated BA by 58% (p < 0.05). Addition of wheat fibre decreased the concentration of chenodeoxycholic acid by 66% (p < 0.05) and isomers of cholic acid by 51% (p < 0.05) in faeces. The mean faecal water concentration of taurine-conjugated BA decreased by 55% when wheat fibre was added (p < 0.05) and the concentration of isomers of deoxycholic acid increased by 39% when ispaghula was supplemented (p < 0.05). The ratio isomeric deoxycholic acid to deoxycholic acid in faecal water increased significantly when wheat fibre was added (p < 0.05). The percentage distribution of secondary and ketonic BA was not influenced by the dietary fibre supplementation. The concentration of BA in faeces and faecal water decreased only by wheat fibre, suggesting that it is superior in obtaining an affect on faecal BA concentration.

Adolescent↗
PubMed1985

Estimation of bile acid pool sizes from their spillover into systemic blood.

We have examined the possibility of assessing primary bile acid pool sizes from the spillover of the bile acids into systemic blood after intestinal exposure to the total endogenous bile acid pool; the studies were carried out in 16 healthy subjects. Bile acid spillover was calculated as the integrated area under the curve of bile acid conjugates in serum of each primary bile acid class in response to a well-defined sustained cholecystokinin-induced stimulus of the enterohepatic circulation for 55 min causing complete gallbladder emptying. Serum levels of each species of primary bile acid conjugates were measured by two specific and sensitive radioimmunoassays, one for conjugated cholate and one for conjugated chenodeoxycholate. Primary bile acid pool sizes determined with [24-14C]cholic acid and [24-14C]chenodeoxycholic acid according to Lindstedt (1957. Acta Physiol. Scand. 40:1-9) served as reference. Bile acid conjugates of both species reached a peak 70 min after the start of the cholecystokinin infusion, probably reflecting simultaneous intestinal absorption of both primary bile acids in this model. Highly significant linear correlations were found between the integrated areas under the curve and primary bile acid pool sizes, which were closer for chenodeoxycholate (n = 16, r = 0.81, P less than 0.001) than for cholate (n = 16, r = 0.74, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Enhanced secretion and low temperature stabilization of a hyperthermostable and Ca2+-independent alpha-amylase of Geobacillus thermoleovorans by surfactants.

AIMS: Selection of suitable surfactants for enhancing and stabilizing alpha-amylase of Geobacillus thermoleovorans. METHODS AND RESULTS: Geobacillus thermoleovorans was cultivated in shake flasks containing 50 ml of starch-yeast extract-tryptone (SYT) medium with/without surfactants. Titres of the enzyme in media were monitored. The enzyme was also preserved at 4 degrees C with/without surfactants and enzyme activities were determined. Among polyethylene glycol (PEGs) of different molecular weights, PEG 8000 (0.5%, w/v) caused a slight increase in the enzyme titre, while Tween-20, Tween-40 and Tween-60 (0.03%, w/v) exerted a significant stimulatory effect on enzyme secretion. In the presence of SDS, Tween-80 and cholic acid (0.03%, w/v), the enzyme production was nearly twofold higher than that in the control. The anionic (SDS, cholic acid) and non-ionic (Tweens) detergents increased the cell membrane permeability, and thus, enhanced alpha-amylase secretion. Furthermore, anionic surfactants exhibited stabilizing effect on the enzyme during preservation at 4 degrees C. CONCLUSIONS: PEG 8000 and the ionic detergents (SDS, cholic acid and Tween-80) were more effective in the solubilization of cell membrane components, and enhancing enzyme yields than the cationic detergents such as CTAB (N,Cetyl-N,N,N-trimethyl ammonium bromide). Further, these surfactants were found to stabilize the enzyme at 4 degrees C. SIGNIFICANCE AND IMPACT OF THE STUDY: The secretion of Ca2+-independent hyperthermostable alpha-amylase was enhanced in the presence of certain anionic and non-ionic detergents in the medium. Furthermore, the surfactants stabilized the enzyme during preservation at 4 degrees C. The use of this enzyme in starch hydrolysis eliminates the addition of Ca2+ in starch liquefaction and its subsequent removal by ion exchange from sugar syrups.

Bacillaceae↗
PubMed1982

Manipulation of testosterone in the neonatal rat and pheromonal emission in the adult.

The question we addressed is why the male rat fails to emit the maternal pheromone when caring for young or when injected with prolactin. Our hypothesis was that exposure to androgen neonatally decreases the prolactin sensitivity of the male liver, making that liver incapable of secreting sufficient cholic acid for pheromonal synthesis. Accordingly, we castrated male rats prior to 2 hr of age and injected female rats with testosterone propionate within 8 days of age. Only those animals that had been spared exposure to androgen neonatally showed evidence of the pheromone when injected with prolactin as adults. Moreover, these same animals exhibited a higher output of cholic acid per g liver than their control counterparts (sham-operated males and vehicle-injected females). We conclude that the sex-related capacity for pheromonal emission is differentiated perinatally and involves the sensitivity of the liver to prolactin and its consequent secretion of cholic acid.

Animals↗
PubMed2003

Method for the quantitative assay of fatty acid-bile acid conjugates by tandem mass spectrometry.

Fatty acid-bile acid conjugates and especially arachidyl amido cholic acid are synthetic molecules that were shown to prevent cholesterol gallstone formation in mice and hamsters as well as to dissolve pre-existing gallstones in mice. To measure these novel compounds we developed a liquid chromatography electrospray tandem mass spectrometry method based on the analysis of 100 microL of plasma with stearyl amido cholic acid (stamchol, 1.5 microM/L) added as internal standard. Repeatable calibrations between 0 and 50 microM/L exhibited consistent linearity and reproducibility. Inter- and intraassay C.V.s were 5.3-11.4% and 2.6-6.4%, respectively, at targeted concentrations of 0.1, 2.3 and 50 microM/L.

Animals↗
PubMed1998

Aminated polysaccharides as bile acid sorbents: in vitro study.

Dextran, pullulan, and microcrystalline cellulose were cross-linked with 1-chloro-2,3-epoxypropane and reacted with N-(1-chloroethyl)-N,N-diethylamine or N-glycidyl-N,N,N-trialkylammonium chloride in order to obtain sorbents containing tertiary amino and/or quaternary ammonium groups. In vitro equilibrium sorption of cholic acid on these sorbents was studied in comparison with Cholestyramine, and in vitro dissociation of ionic complexes of cholic acid-sorbents was determined under dynamic conditions. The sorption capacity and the affinity of these sorbents for cholic acid were investigated in relation to the nature of the polymeric support, the swelling porosity of sorbent, the basicity of amino groups, and the nature of the substituents at the nitrogen atom. The maximum sorption capacity increases with the increase in amino group content, their basicity, and the length of alkyl substituents at the nitrogen atom. The affinity for cholic acid of all polysaccharide-based sorbents is higher than that of Cholestyramine. Dextran-based sorbents display the highest sorption affinity. It was found that there exists an optimum swelling porosity for the polysaccharide sorbents to attain the highest affinity for cholic acid. The dissociation rate of ionic complexes depends also on the nature of the polysaccharide and the swelling porosity and its lower for sorbents with higher sorption affinity.

Absorption↗
PubMed1973

Triketocholanoic (dehydrocholic) acid. Hepatic metabolism and effect on bile flow and biliary lipid secretion in man.

[24-(14)C]Dehydrocholic acid (triketo-5-beta-cholanoic acid) was synthesized from [24-(14)C]cholic acid, mixed with 200 mg of carrier, and administered intravenously to two patients with indwelling T tubes designed to permit bile sampling without interruption of the enterohepatic circulation. More than 80% of infused radioactivity was excreted rapidly in bile as glycine- and taurine-conjugated bile acids. Radioactive products were identified, after deconjugation, as partially or completely reduced derivatives of dehydrocholic acid. By mass spectrometry, as well as chromatography, the major metabolite (about 70%) was a dihydroxy monoketo bile acid (3alpha,7alpha-dihydroxy-12-keto-5beta-cholanoic acid); a second metabolite (about 20%) was a monohydroxy diketo acid (3alpha-hydroxy-7,12-di-keto-5beta-cholanoic acid); and about 10% of radioactivity was present as cholic acid. Reduction appeared to have been sequential (3 position, then 7 position, and then 12 position) and stereospecific (only alpha epimers were recovered). Bile flow, expressed as the ratio of bile flow to bile acid excretion, was increased after dehydrocholic acid administration. It was speculated that the hydroxy keto metabolites are hydrocholeretics. The proportion of cholesterol to lecithin and bile acids did not change significantly after dehydrocholic acid administration. In vitro studies showed that the hydroxy keto metabolites dispersed lecithin poorly compared to cholate; however, mixtures of cholate and either metabolite had dispersant properties similar to those of cholate alone, provided the ratio of metabolite to cholate remained below a value characteristic for each metabolite. These experiments disclose a new metabolic pathway in man, provide further insight into the hydrocholeresis induced by keto bile acids, and indicate the striking change in pharmacologic and physical properties caused by replacement of hydroxyl by a keto substituent in the bile acid molecule.

Bile↗
PubMed1994

Changes in bile acids metabolism during rat hepatocarcinogenesis: causative or unrelated?

In the present paper, we have aimed at studying the variations in the metabolism of bile acids occurring during an hepatocarcinogenic process induced in male Wistar Rats by the biphasic protocol of Solt and Farber. Bile acids concentrations was measured in the liver. The most significant changes have been observed 5 weeks after the beginning of the treatment, it means one week after the selection treatment consisting in 2-acetylaminofluorene administration: the increase in cholic acid, and of its intestinal metabolite, deoxycholic acid, and of alpha- and beta- muricholic acids, are likely to be a consequence of an acute effect of 2-acetylaminofluorene. To test for the putative implication of liver bile acids modifications in the selection effect of 2-acetylaminofluorene, diethyl-nitrosamine-pretreated rats were fed a diet containing 1% lithocholic acid, a treatment that induces essentially the same qualitative changes in liver bile acids, as 2-acetylaminofluorene does: no selection effect of lithocholic acid could be demonstrated. These results suggest that changes in bile acid metabolism occurring early in hepatocarcinogenesis are more likely to be secondary than causative events. The same conclusion comes from the results obtained later on in the process, where there is only a high increase in liver cholic acid and deoxycholic acid concentrations.

2-Acetylaminofluorene↗
PubMedDate not supplied

Enhancing the "stickiness" of bile acids to cross-linked polymers: a bioconjugate approach to the design of bile acid sequestrants.

A series of cross-linked polymers have been synthesized by reaction of 2% cross-linked, chloromethylated polystyrene with a tertiary amine derivative (7) of cholic acid (prepared by reaction of cholic acid methyl ester with N,N-dimethyl-ethylenediamine), followed by exhaustive quaternization with trimethylamine. Increased loadings of 7 result in enhanced binding of taurocholate ion and a decrease in its rate of release upon exposure to 50 mM aqueous NaCl. Examination of particle-size effects indicates that film diffusion and particle diffusion both contribute to the observed kinetics. Interruption tests that were carried out confirmed that particle diffusion is kinetically important. The relevance of this bioconjugate approach to the design of bile acid sequestrants for the treatment of hypercholesterolemia is briefly discussed.

Anion Exchange Resins↗
PubMed1997

Cholylglycine hydrolase and 7alpha-dehydroxylase optimum assay conditions in vitro and caecal enzyme activities ex vivo.

Increasing evidence implicates deoxycholic acid (DCA) in the pathogenesis of cholesterol-rich gallbladder stones. However, relatively little is known about the activities of the two intestinal bacterial enzymes (cholylglycine hydrolase and cholic acid 7alpha-dehydroxylase) responsible for the deconjugation and subsequent dehydroxylation of conjugated cholic acid (CA), to form DCA. We, therefore, established optimal reaction conditions for measuring the activities of these two enzymes in vitro, and applied these conditions to the determination of the enzymes in caecal aspirates from six subjects undergoing clinically-indicated colonoscopy. With respect to cholylglycine hydrolase activity: zero order kinetics were found over 20 min at 37 degrees C (pH optimum 4.0), with Km and Vmax values of 1.66 mmol/l and 0.90 mmol CA min(-1) mg prot(-1), respectively. For cholic acid 7alpha-dehydroxylation: zero order kinetics were found over 7.5 min at 37 degrees C, under anaerobic conditions (pH optimum 8.0), with Km and Vmax values of 5.23 x 10(-8) mol/l and 1.88 x 10(-7) mol DCA min(-1) mg prot(-1), respectively. Applying these reaction conditions to the caecal aspirates, endogenous cholylglycine hydrolase activities ranged from 0.49 to 2.43 units (mg protein[-1] min[-1]) and CA 7alpha-dehydroxylase activities from 1.75 to 5.82 x 10(-7) units (mg protein[-1] min[-1]). This study is unique in assaying quantitatively both the deconjugation and dehydroxylation enzyme activities in human caecal samples--an essential first step to further studies of intestinal bacterial enzymes in the pathogenesis of cholesterol gallstone disease.

Amidohydrolases↗
PubMed1995

Serum conjugated bile acid profile during intrahepatic cholestasis of pregnancy.

BACKGROUND/AIMS: Intrahepatic cholestasis of pregnancy is a specific liver disease of pregnancy of unknown cause. The serum bile acid profile has not been clearly described in this disease and the aim of this study was to investigate the serum conjugated bile acid profile. METHODS: Thirteen patients with intrahepatic cholestasis of pregnancy were studied. Ten patients had been treated with natural progestatin before the onset of pruritus. The glyco- and tauroconjugated bile acids were quantified by high-performance liquid chromatography and direct spectrometric detection at 199 nm. RESULTS: There was no difference between total bile acid concentrations measured by high-performance liquid chromatography (43.5 +/- 22.6 microM, mean +/- S.D.) or by an enzymatic procedure (43.4 +/- 24.6 microM), indicating a low concentration of free bile acids. Primary bile acids represented 88% of total bile acids, i.e. 72.7% for cholic acid and 15.3% for chenodeoxycholic acid. For both cholic and chenodeoxycholic acids glyco- and tauroconjugates were equivalent. Secondary bile acids represented 11.3% of total bile acids. Ursodeoxycholic acid was identified at very low concentrations in only three samples. CONCLUSIONS: We conclude that in intrahepatic cholestasis of pregnancy primary bile acids are very predominant.

Adult↗
PubMed2002

Participation of two members of the very long-chain acyl-CoA synthetase family in bile acid synthesis and recycling.

Bile acids are synthesized de novo in the liver from cholesterol and conjugated to glycine or taurine via a complex series of reactions involving multiple organelles. Bile acids secreted into the small intestine are efficiently reabsorbed and reutilized. Activation by thioesterification to CoA is required at two points in bile acid metabolism. First, 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid, the 27-carbon precursor of cholic acid, must be activated to its CoA derivative before side chain cleavage via peroxisomal beta-oxidation. Second, reutilization of cholate and other C24 bile acids requires reactivation prior to re-conjugation. We reported previously that homolog 2 of very long-chain acyl-CoA synthetase (VLCS) can activate cholate (Steinberg, S. J., Mihalik, S. J., Kim, D. G., Cuebas, D. A., and Watkins, P. A. (2000) J. Biol. Chem. 275, 15605-15608). We now show that this enzyme also activates chenodeoxycholate, the secondary bile acids deoxycholate and lithocholate, and 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid. In contrast, VLCS activated 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoate, but did not utilize any of the C24 bile acids as substrates. We hypothesize that the primary function of homolog 2 is in the reactivation and recycling of C24 bile acids, whereas VLCS participates in the de novo synthesis pathway. Results of in situ hybridization, topographic orientation, and inhibition studies are consistent with the proposed roles of these enzymes in bile acid metabolism.

Bile Acids and Salts↗
PubMed1996

Analysis of bile acids in urine specimens from healthy humans: determination of several bile acids with beta-hydroxyl and carbonyl groups.

Urinary bile acids of 39 healthy male undergraduates were analyzed by capillary gas chromatography and capillary gas chromatography-mass spectrometry. 3 alpha-Hydroxy-12-oxo-5 beta-cholanoic acid, 3 alpha, 12 beta-dihydroxy-5 beta-cholanoic acid, 3 beta, 7 alpha-dihydroxy-5 beta-cholanoic acid, and 3 alpha, 7 alpha, 12 beta-trihydroxy-5 beta-cholanoic acid, in addition to known bile acids, were identified and then quantified. The major part of the urinary bile acids was occupied by secondary bile acids. Every 7 beta-hydroxylated bile acid species was found in more than 80% of the subjects. The bile acid detected in the largest amount was 3 alpha-hydroxy-12-oxo-5 beta-cholanoic acid. The metabolites of cholic acid were quantitatively more predominant than those of chenodeoxycholic acid. These results indicate that bile acids with beta-hydroxyl and carbonyl groups at the C-3,7 and/or 12 positions are usual bile acids usually found in the urine of healthy humans. It is concluded that the occurrence of these bile acids is an effect of the intestinal bacterial flora and living conditions.

Adult↗