[Synthesis of conjugated bile acids].
Explore the source record for details and available documents.
Bile Acids and Salts↗
SEARCH · PubMed Health
Results for “Glycodeoxycholic Acid”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Concentrations of glycine- and taurine-conjugated bile acids in portal and systemic venous serum in man.
Concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid in portal and systemic venous serum and in bile were measured in eight subjects undergoing elective cholecystectomy. Mean concentrations in systemic serum ranged from 0.07 to 0.17 mumol/l, in portal serum from 0.49 to 2.09 mumol/l, and in bile from 2.72 to 17.2 mmol/l. The percentage content of trihydroxy-bile acid conjugates in bile (49%) and in portal serum (51%) was higher than in systemic serum (35%) (P less than 0.001). The estimated hepatic fractional uptake of glycocholic acid (mean, 83%) and of taurocholic acid (83%) was higher than the uptakes of the dihydroxy-bile acid conjugates (60-68%). The percentage contents of glycine-conjugated bile acids in systemic serum (mean, 66%), portal serum (62%), and bile (65%) were not significantly different.
Adult↗
Studies on steroids. CLXXXVII. Determination of serum bile acids by high-performance liquid chromatography with fluorescence labeling.
A method for the simultaneous determination of bile acids in serum by high-performance liquid chromatography (HPLC) with fluorescence labeling is described. The bile acid fraction was obtained from a serum specimen by passing it through a BondElut cartridge. Bile acids were derivatized quantitatively into the fluorescent compounds through the hydroxyl group at C-3 by treatment with 1-anthroyl nitrile in the presence of quinuclidine in acetonitrile. These derivatives were separated into the free, glycine- and taurine-conjugate fractions by ion-exchange chromatography on a lipophilic gel, piperidinohydroxypropyl Sephadex LH-20. Subsequent resolution of each fraction into cholate, ursodeoxycholate, chenodeoxycholate, deoxycholate and lithocholate was attained by HPLC on a Cosmosil 5C18 column using 0.3% potassium phosphate buffer (pH 6.0)--methanol (1:5) and 0.1% potassium phosphate buffer (pH 6.0)--methanol (1:8) as mobile phases. The anthroyl bile acids were monitored by fluorescence detection (excitation wavelength 370 nm; emission wavelength 470 nm), the limit of detection being 20 fmol. The proposed method proved to be applicable to the quantitation of bile acids in serum with satisfactory reliability and sensitivity.
Bile Acids and Salts↗
Metabolism of bile acids by strains of Acinetobacter anitratum and Acinetobacter lwoffii.
The activity of two species of bacteria: Acinetobacter anitratum and Acinetobacter lwoffii, isolated from jejunum of patients with achlorhydria and Reichel-Polya resection towards bile salts was investigated. These species were not previously tested from this view point. All strains tested hydrolyzed bile salts; conjugates of deoxycholic acid were hydrolyzed more readily than those of cholic acid. This feature may be used as a bacteriological taxonomic criterion.
Acinetobacter↗
Thin-layer chromatographic separation of conjugates of ursodeoxycholic acid from those of litho-, chenodeoxy-, deoxy-, and cholic acids.
Separation of the glycine and taurine conjugates of ursodeoxycholic acid from those of lithocholic acid, chenodeoxycholic acid, deoxycholic acid, and cholic acid by thin-layer chromatography is described. Thus, on running a silica gel G plate first in a solvent system of n-butanol-water 20:3 and then in a second solvent system of chloroform-isopropanol-acetic acid-water 30:20:4:1, all the above-mentioned conjugated bile acids are separated from one another. The application of this method to study the change in the biliary bile acid conjugation pattern in ursodeoxycholic acid-fed gallstone patients is described.
Chenodeoxycholic Acid↗
A model of experimental acute necrotizing pancreatitis.
BACKGROUND: A model of moderate acute necrotizing pancreatitis is essential for the study of the pathophysiology of the disease and novel therapies. We tried to establish a model of bile salt-induced acute necrotizing pancreatitis in rats. METHODS: Acute pancreatitis was induced by retrograde infusion of bile salt into the cannulated pancreatobiliary duct. Twenty-six rats wee divided into 3 groups. Group I (n = 8) received 0.2 ml of glycodeoxycholic acid (GDOC) 10 mmol/l; group II (n = 10) 0.2 ml of 2.5% sodium taurodeoxycholate (NaTDC); group III (n = 8) the mixture of 0.2 ml GDOC 10 mmol/l and 10 U enterokinase. Serum levels of amylase and lipase, hematocrit, mean arterial pressure and heart rate were determined at baseline and 5 hours later. Then the pancreas was removed for histopathology and grading (0-3; absent-severe) with regard to leukocyte infiltration, edema, necrosis, hemorrhage and acinar cell vacuolization. RESULTS: Serum levels of amylase and lipase increased significantly in 5 hours in all the groups. Serum amylase levels were significantly lower in group III than in group II. No significant difference of serum lipase was found among the groups. Group II had the highest scores of necrosis and acinar cell vacuolization, whereas group III had the highest scores of leukocyte infiltration and edema. The degree of necrosis was significantly more severe in group II than in group I. The hematocrit increased significantly in 5 hours in groups I and II. The mean arterial pressure in 5 hours decreased significantly in group I. There was no significant difference of the changes of heart rate in 5 hours among 3 groups. CONCLUSIONS: Intraductal infusion of NaTDC was a good method to induce moderate acute necrotizing pancreatitis in rats. GDOC caused mild pancreatitis, and pancreatic injury was aggravated when enterokinase was added. The severity of pancreatic histopathology was not correlated with the changes of serum levels of pancreatic enzymes, hematocrit or mean arterial pressure at the early stage of pancreatitis.
Acute Disease↗
Comparison of hypolipidemic effect of refined konjac meal with several common dietary fibers and their mechanisms of action.
The effects of RKM in comparison with pectin, algin and agar on lipid levels in serum and liver and on liver histopathology in rats were studied. In addition, the effects of all the tested materials on the composition and output of fecal bile acid were observed. All four kinds of dietary fiber were given at a level of 5% of diet to young male rats of Wistar strain fed on a lipid-rich diet containing 5% lard, 1% cholesterol and 0.25% cholate. All the dietary fibers tested have similar effects on serum lipid composition. In all groups, these substances prevented increases in total cholesterol in fasting serum, but the level of triglyceride was unchanged. The concentrations of total cholesterol and triglyceride in the liver were lower in the RKM group than in the control group and the other three groups. Hepatic histopathological examination also showed the most significant lipotropic effect in the RKM group. The daily output of fecal bile acids (CDCA + GDCA) was significantly increased in the four experimental groups than in the normal group and the control group. The increase of CDCA was more significant than GDCA, suggesting that the increase of fecal bile acids, especially CDCA, may be one of the mechanisms by which RKM and the other three dietary fibers exerts a hypocholesterolemic effect.
Agar↗
Prophylactic octreotide reduces the severity of histopathologic changes and hemodynamic shock in early taurodeoxycholate-induced experimental pancreatitis.
The findings related to the effects of somatostain and octreotide in experimental and clinical acute pancreatitis are so far inconclusive. In this study, we examined the early effects of prophylactic octreotide in acute experimental pancreatitis. Serum levels of amylase and lipase, pancreatic histopathology and systemic hemodynamic profiles, including mean arterial pressure, cardiac index, systemic vascular resistance and heart rate, were evaluated 5 hours after glycodeoxycholic acid (GDOC) or sodium taurodeoxycholate (TDC)-induced pancreatitis with or without prophylactic octreotide (10 micrograms/Kg) in rats, GDOC and TDC induced mild and severe pancreatitis, respectively. Octreotide significantly reduced serum levels of amylase and lipase at 5 hours in GDOC and TDC-induced pancreatitis. Octreotide significantly reduced the severity of pancreatic edema, necrosis and hemorrhage in TDC-induced pancreatitis. In addition, hemodynamic shock in TDC-induced pancreatitis was improved significantly by the administration of octreotide (mean arterial pressure 70.3 +/- 7.7 vs. 95.0 +/- 3.5 mmHg, p < 0.05; cardiac index 16.7 +/- 2.5 vs. 24.0 +/- 5.1 ml.min-1. 100 g-1, p < 0.05). However, octreotide did not show significant beneficial effect in pancreatic histopathology and hemodynamics in GDOC-induced pancreatitis. Thus we conclude that prophylactic octreotide improves pancreatic histopathology and hemodynamic shock in TDC-induced pancreatitis.
Acute Disease↗
Bile acid binding to dietary casein: a study in vitro and in vivo.
1. Studies were carried out in vitro using an ultracentrifugation method to quantify bile acid binding to the different components of a Lundh test meal, and to determine what factors influence bile acid binding to one of the components (casein). We validated the ultracentrifugation method by showing good agreement with the equilibrium dialysis method. Studies were carried out in vivo on jejunal aspirate from 10 ileal resection patients in order to determine whether bile acid binding to casein could be demonstrated, and whether this influenced aqueous-phase bile acid and fatty acid concentrations. 2. In vitro, the Lundh test meal was found to adsorb bile acid. The protein content of the meal (casein) alone accounted for this binding, which was abolished by use of casein hydrolysate. The binding to casein was a saturable process. Both binding affinity and binding capacity were significantly greater for taurocholate at pH 4.5 than at pH 6.5, and for dihydroxylated than for trihydroxylated bile acid, suggesting that hydrophobic bonding was involved. 3. In vivo, jejunal samples aspirated at pH greater than 6 from 10 ileal resection patients showed 25% binding of bile acid to protein. On substitution of amino acids for casein, mean binding was reduced to 16% (P less than 0.05), residual binding being attributed to endogenous protein. This was associated with an increase in fatty acid solubilization from 28% to 60% (P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Hep G2 cells: a model for studies on regulation of human cholesterol 7alpha-hydroxylase at the molecular level.
The present study examines the feedback control governing human cholesterol 7alpha-hydroxylase mRNA expression in the human hepatoblastoma cell line, Hep G2. Glycochenodeoxycholate (GCDC) and glycodeoxycholate, hydrophobic bile salts, decreased cholesterol 7alpha-hydroxylase mRNA levels and bile acid synthesis in a concentration-dependent (76 +/- 8%, P<0.001, and 48 +/- 3%, P<0.01, respectively) and time-dependent manner. Cholesterol 7alpha-hydroxylase mRNA levels were repressed with a half-maximal inhibitory concentration of <12.5 microM by GCDC and a half-life of 30 min by 100 microM of the bile acid. The addition of actinomycin D (10 microgram/ml) alone or in combination with GCDC (100 microM) led to similar concentration-and time-dependent suppression of cholesterol 7alpha-hydroxylase mRNA. Glycocholate (100 microM), not internalized based on lack of uptake of a fluorescent cholate analogue, had no effect on cholesterol 7alpha-hydroxylase mRNA or total bile acid synthesis. In cultures transfected with a rat cholesterol 7alpha-hydroxylase promoter construct, reporter gene activity was decreased (31%, P<0.01) by GCDC (100 microM). Hep G2 cells maintain the intracellular machinery to express and rapidly regulate human cholesterol 7alpha-hydroxylase by hydrophobic bile acids. These data suggest that Hep G2 cells will support functional studies of the human cholesterol 7alpha-hydroxylase gene.
Animals↗
Studies in bile salt solutions. Deoxycholate stimulation of human milk lipase.
Stimulation of human milk lipase by deoxycholate and its taurine and glycine conjugates was demonstrated by measuring the esterolysis reaction of 4-nitrophenylacetate. The steroidal surfactants did not bind strongly to the polar substrate but they did bind effectively to a hydrophobic site on the enzyme and these bile salt-enzyme complexes were effective catalysts. These results are compared with those for stimulation of the enzyme by cholate surfactants and it has been demonstrated that the absence of a 7 alpha-OH substituent on the steroid nucleus does not prevent stimulation of either the esterolytic or lipolytic activity of the enzyme.
Deoxycholic Acid↗
Composition of aqueous solutions containing sodium glycocholate and glycodeoxycholate.
Composition and existence range of aggregates formed by sodium glycocholate and glycodeoxycholate contemporary present in aqueous micellar and premicellar solutions were investigated. Solubility measurements of lead (II) glycocholate and glycodeoxycholate give analytical concentration of lead (II) and glycocholate and glycodeoxycholate, respectively. Electromotive force measurements provide the free concentration of hydrogen, sodium and lead (II) ions. Experimental data obtained at 25 degrees C and at three different concentrations of N(CH3)4Cl, used as a constant ionic medium, can be explained by assuming the presence of aggregates of different composition depending on the reagent and ionic medium concentrations. Next to two species containing only glycocholate or glycodeoxycholate, the presence of aggregates formed with the contemporary participation of both bile anions in different ratios was assumed. Species with the hydrogen ion participation are not present in appreciable quantity in the investigated concentration range. As expected, the size of aggregates increases by increasing reagent and ionic medium concentration. Most of the species can be explained with a "core + link" mechanism, where all the glycocholate aggregation numbers are even, while those of glycodeoxycholate are always multiple of three. Analogy and difference with aggregates formed by the two bile anions separately are discussed.
Glycocholic Acid↗
Effects of bile salts on the plasma membranes of isolated rat hepatocytes.
The conjugated trihydroxy bile salts glycocholate and taurocholate removed approx. 20--30% of the plasma-membrane enzymes 5'-nucleotidase, alkaline phosphatase and alkaline phosphodiesterase I from isolated hepatocytes before the onset of lysis, as judged by release of the cytosolic enzyme lactate dehydrogenase. The conjugated dihydroxy bile salt glycodeoxycholate similarly removed 10--20% of the 5'-nucleotidase and alkaline phosphatase activities, but not alkaline phosphodiesterase activity; this bile salt caused lysis of hepatocytes at approx. 10-fold lower concentrations (1.5--2.0mM) than either glycocholate or taurocholate (12--16mM). At low concentrations (7 mM), glycocholate released these enzymes in a predominantly particulate form, whereas at higher concentrations (15 mM) glycocholate further released these components in a predominantly 'soluble' form. Inclusion of 1% (w/v) bovine serum albumin in the incubations had a small protective effect on the release of enzymes from hepatocytes by glycodeoxycholate, but not by glycocholate. These observations are discussed in relation to the possible role of bile salts in the origin of some biliary proteins.
Animals↗
Effects of alpha 1-acid glycoprotein on acute pancreatitis and acute lung injury in rats.
alpha 1-Acid glycoprotein (AAG), a highly negatively charged glycoprotein, well known for its capillary stabilizing effect, was tested in rat models of acute edematous pancreatitis, acute hemorrhagic-necrotizing pancreatitis, and acute respiratory distress syndrome (ARDS). In cerulein-elicited edematous pancreatitis AAG improved histological alterations at 200 mg/kg i.v. and plasma amylase activity at 1800 or 4200 mg/kg i.v. All other parameters (edema, plasma lipase) were not affected in a biologically relevant manner. In glycodeoxycholic acid-induced hemorrhagic-necrotizing pancreatitis AAG was without effect on parameters measured (plasma amylase, plasma lipase activity, histological scores) at 1800 or 4200 mg/kg i.v. At the extremely high dose of 1500 mg/kg i.v. plasma amylase and lipase levels were decreased. In lipopolysaccharide-mediated ARDS, AAG was tested at 50, 200 or 600 mg/kg i.v. AAG, but also the placebo formulation decreased the myeloperoxidase content in the bronchoalveolar lavage fluid. Histological alterations were improved by AAG, however, not by the placebo formulation. Lung water content was not significantly influenced by AAG, whereas Evans blue extravasation was significantly diminished by all three doses of AAG. It is concluded that the edematous pancreatitis is the first in vivo condition with increased extravascular fluid accumulation, in which AAG is not effective. Based on data presented here and literature data, there is evidence for a beneficial effect of AAG in acute lung injury.
Acute Disease↗
Enhancement of maximal bilirubin excretion by bile salts in the anaesthetized rabbit.
The influence of glycodeoxycholate, taurocholate and dehydrocholate on the maximal hepatic excretion of bilirubin was investigated in rabbits anaesthetized with sodium pentobarbitone. Biliary secretion of dehydrocholate was much less than that of the other two bile salts, which could be explained by its metabolism in the hepatocytes. Glycodeoxycholate and dehydrocholate had a greater choleretic effect than taurocholate. Only glycodeoxycholate and taurocholate increased the secretion of biliary lipids, suggesting that dehydrocholate or its metabolites were unable to form micelles. All three bile salts, however, increased maximal bilirubin excretion to a similar extent. These results indicate that the action of bile salts on the excretion of bilirubin cannot be fully explained in terms of binding to mixed micelles.
Anesthesia, General↗
A comparison of the effect of bile salts on maximal hepatic excretion of certain organic anions in the rabbit under urethane and pentobarbitone.
The influence of two different anaesthetics, sodium pentobarbitone and ethyl urethane, on the enhancement of maximal bilirubin and bromosulphthalein (BSP) excretion induced by bile salts was investigated in rabbits. Two micelle-forming (glycodeoxycholate and taurocholate) and one non-micelle-forming (dehydrocholate) bile salts were used. Under urethane anaesthesia the bile flow was lower than with pentobarbitone, and this could be attributed to a smaller bile salt non-dependent fraction of secretion. The effect of bile salts on the maximal excretion of the two organic anions appeared more clearly related to some kind of micelle interaction in rabbits anaesthetized with urethane than in pentobarbitone-anaesthetized animals. Thus, under urethane, infusions of glycodeoxycholate substantially increased the maximal excretion of bilirubin and BSP, taurocholate exerted an intermediate and dehydrocholate only a small effect. Under pentobarbitone, however, the augmenting action of all three bile salts was similar. The influence of bile salts on the endogenous excretion of bile pigments in experiments in which the test anion was BSP showed corresponding differences dependent upon the anaesthetic used. Possible explanations for those results are discussed.
Anesthesia, General↗
Membrane fluidity and bile salt damage.
The lysis, by bile salts, of membranes of different fluidities was studied; it was shown that membranes of low fluidity were less readily lysed than membranes of higher fluidity. Membrane fluidity levels were controlled (i) by the use of erythrocytes, from different species, systematically differing in their lipid composition; (ii) by using each membrane at a range of temperatures; and (iii) by incorporating into the membranes the fluidizing agent, benzyl alcohol, at a range of concentrations. Membrane fluidity (and order) in each case was monitored by measuring the degree of polarization of fluorescence from the hydrophobic probe molecule, 1,6-diphenyl-1,3,5-hexatriene. The response of lytic behaviour to modulations of membrane fluidity also indicated a difference between the bile salts, glycodeoxycholate and glycocholate; the former initiates lysis close to (at or below) its critical micellar concentrations whereas the latter only causes lysis above, and often substantially above, its critical micellar concentration. In their respective ranges of lytic concentrations, both bile salts are far less effective with membranes of low fluidity. The results are discussed with regard to the features of a membrane which would be expected to be resistant to high concentrations of bile salts in vivo, i.e., the plasma membranes of the bile canaliculus and lumenal surface of biliary tract cells.
Animals↗
TR146 cells grown on filters as a model of human buccal epithelium: III. Permeability enhancement by different pH values, different osmolality values, and bile salts.
The aim of the present study was to evaluate the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability enhancement by different pH values, different osmolality values or bile salts. For this purpose, the increase in the apparent permeability (P(app)) of the hydrophilic marker mannitol due to exposure to solutions with pH values or osmolality values different from the physiological values was studied. As in studies with solutions of either taurocholate (TC), glycocholate (GC) or glycodeoxycholate (GDC) the results were compared to the increase in P(app) of mannitol obtained in analog studies using porcine buccal mucosa in an Ussing chamber. The effect of the exposure on the electrical resistance of the TR146 cell culture model and the porcine buccal mucosa was measured, and the degree of protein leakage due to GC exposure was investigated in the TR146 cell culture model. The porcine buccal mucosa was approximately ten times less permeable to mannitol than the TR146 cell culture model. The P(app)TC. Increased P(app) values correlated with a decrease in the electrical resistance of the TR146 cell culture model and the porcine buccal mucosa. GC was shown to induce concentration dependent protein leakage in the TR146 cell culture but only from the site of application, and the results indicate that duration of exposure further than 120 min was of minor importance. The present results indicate that the TR146 cell culture model may be a suitable in vitro model for efficacy studies and mechanistic studies of enhancers with potential use in human buccal drug delivery.
Animals↗