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Results for “Glycodeoxycholic Acid”

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PubMed1987

Effect of epidermal growth factor on growth and postnatal development of the rabbit liver.

The effect of epidermal growth factor (EGF) on the postnatal development of the liver was examined. New Zealand White rabbits received 40 micrograms.kg-1.day-1 EGF from days 3 to 17 of age either intraperitoneally or orogastrically, whereas controls received saline. At days 18-20, animals underwent cannulation of the common duct using halothane anesthetic. Biliary output was measured directly for three 1-h periods: under basal conditions and in response to intravenous infusion of exogenous glycodeoxycholic acid at 0.75 and 1.5 mumol.min-1.kg-1, respectively. The bile salt pool size was measured by isotope dilution. Final mean body weight of intraperitoneal and orogastric groups did not differ from controls. Liver we weight, DNA, and protein content were significantly increased in intraperitoneally treated animals without morphological or biochemical evidence of fat deposition. Both intraperitoneal and orogastric EGF significantly increased bile salt secretion in the basal period and as a response to exogenous bile acid infusion. Bile flow was significantly increased in response to 1.5 mumol.min-1.kg-1 infusion of glycodeoxycholic acid. The bile salt pool was increased by both intraperitoneal and orogastric EGF. Administration of EGF resulted in a precocious development of glucokinase (EC 2.7.1.2) activity in the liver. EGF had no effect on serum cortisol, corticosterone, triiodothyronine, thyroxine, or free thyroxine levels. These findings suggest that in the neonatal period EGF can promote hepatic growth and maturation.

Animals↗

PubMed2003

Feedback regulation of bile acid synthesis in primary human hepatocytes: evidence that CDCA is the strongest inhibitor.

Primary human hepatocytes were used to elucidate the effect of individual bile acids on bile acid formation in human liver. Hepatocytes were treated with free as well as glycine-conjugated bile acids. Bile acid formation and messenger RNA (mRNA) levels of key enzymes and the nuclear receptor short heterodimer partner (SHP) were measured after 24 hours. Glycochenodeoxycholic acid (GCDCA; 100 micromol/L) significantly decreased formation of cholic acid (CA) to 44% +/- 4% of controls and glycodeoxycholic acid (GDCA) decreased formation of CA to 67% +/- 11% of controls. Glycoursodeoxycholic acid (GUDCA; 100 micromol/L) had no effect. GDCA or glycocholic acid (GCA) had no significant effect on chenodeoxycholic acid (CDCA) synthesis. Free bile acids had a similar effect as glycine-conjugated bile acids. Addition of GCDCA, GDCA, and GCA (100 micromol/L) markedly decreased cholesterol 7alpha-hydroxylase (CYP7A1) mRNA levels to 2% +/- 1%, 2% +/- 1%, and 29% +/- 11% of controls, respectively, whereas GUDCA had no effect. Addition of GDCA and GCDCA (100 micromol/L) significantly decreased sterol 12alpha-hydroxylase (CYP8B1) mRNA levels to 48% +/- 5% and 61% +/- 4% of controls, respectively, whereas GCA and GUDCA had no effect. Addition of GCDCA and GDCA (100 micromol/L) significantly decreased sterol 27-hydroxylase (CYP27A1) mRNA levels to 59% +/- 3% and 60% +/- 7% of controls, respectively, whereas GUDCA and GCA had no significant effect. Addition of both GCDCA and GDCA markedly increased the mRNA levels of SHP to 298% +/- 43% and 273% +/- 30% of controls, respectively. In conclusion, glycine-conjugated and free bile acids suppress bile acid synthesis and mRNA levels of CYP7A1 in the order CDCA > DCA > CA > UDCA. mRNA levels of CYP8B1 and CYP27A1 are suppressed to a much lower degree than CYP7A1.

Adult↗

PubMed1999

Effects of octreotide on acute pancreatitis of varying severity in rats.

OBJECTIVE: To find out the effects of the octreotide on the course of acute pancreatitis in rats. DESIGN: Prospective laboratory study. SETTING: Medical school, Turkey ANIMALS: 184 Sprague-Dawley rats, 120 of which were randomly allocated into 8 groups of 15 each for the survival study, and the remainder of which were randomly allocated into 8 groups of 8 rats each for assessment of biochemical variables and histological score. INTERVENTIONS: The same 8 groups were used for the two parts of the study: saline alone (control), octreotide alone (control), oedematous pancreatitis induced by cerulein with and without octreotide, moderate pancreatitis induced by low-dose glycodeoxycholic acid and cerulein with and without octreotide, and severe pancreatitis induced by high-dose glycodeoxycholic acid and cerulein with and without octreotide. MAIN OUTCOME MEASURES: Mortality, results of biochemical tests, and histological score. RESULTS: No rats in the control groups died. Of those with oedematous pancreatitis 1 died that had not been given octreotide (7%) and 2 that had (13%). In the moderate pancreatitis groups 4 that had not been given octreotide died (27%) compared with one that had (7%). In the severe pancreatitis group 7 that had not had octreotide died (46%) compared with 6 that had (40%). Octreotide caused a reduction in serum amylase and lactate dehydrogenase activity in all groups, but reduced aspartate aminotransferase only in those rats with moderate pancreatitis. It prevented hypocalcaemia in rats with severe pancreatitis, but had no effect on serum electrolyte concentrations, alkaline phosphatase activity, or blood gas analyses. Rats with moderate pancreatitis that had been given octreotide had less tissue oedema, acinar necrosis, and inflammatory cell infiltration. In those with severe pancreatitis there was less tissue oedema but more acinar necrosis. CONCLUSION: If octreotide is given early in the course of the disease it may result in improved outcome, but it seems to be ineffective in severe pancreatitis in which acinar necrosis is already established.

Acute Disease↗

PubMed2001

Combined use of Lactobacillus reuteri and soygerm powder as food supplement.

AIMS: The survival of Lactobacillus reuteri when challenged with glycodeoxycholic acid (GDCA), deoxycholic acid (DCA) and soygerm powder was investigated. Moreover, the impact of Lact. reuteri on the bioavailability of isoflavones present in soygerm powder was examined. METHODS AND RESULTS: The strain experienced a die-off when adding 2 or 3 mmol l-1 bile salts, with more pronounced effects in the case of DCA. By means of a haemolysis test it was shown that toxicity could be due to membrane damage. When 4 g l-1 soygerm powder was added, the Lactobacillus strain survived the bile salt burden better (P < or = 0.05) and the membrane damage in the haemolysis test decreased (P < or = 0.05). The Lact. strain cleaved beta-glycosidic isoflavones during fermentation of milk supplemented with soygerm powder. CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: The interactions between the Lactobacillus strain and soygerm powder suggest that combining both in fermented milk can exhibit advantageous probiotic effects. The relevance of the combination of the strain and the soygerm powder should be studied under more relevant physiological conditions.

Animals↗

PubMed1998

Evaluation and optimisation of separation buffers for the determination of corticosteroids with micellar electrokinetic capillary chromatography (MECC).

Separation buffers for the determination of the corticosteroids cortisone, hydrocortisone, prednisone and prednisolone with micellar electrokinetic chromatography were developed with respect to separation efficacy and the migration times, depending on the type and the concentration of the organic modifier acetonitrile as well as on the addition of gamma-cyclodextrin. The buffer containing 50 mM SDS and 16% (v/v) acetonitrile enables the rapid profiling of prednisolone together with cortisone and prednisone. Addition of gamma-cyclodextrin alters the elution sequence, but does not further enhance resolution of the corticosteroids. Baseline separation at long migration times for cortisone, hydrocortisone, prednisone and prednisolone is achieved with a buffer containing 50 mM each of SDS, dehydrocholic acid sodium salt and glycodeoxycholic acid sodium salt.

Acetonitriles↗

PubMed1992

Pulmonary injury in acute experimental pancreatitis correlates with elevated levels of free fatty acids in rats.

Since some authors have stated a certain role for so-called "free fatty acids" (FFA) in the pathogenesis of AP and the subsequent systemic complications we tried to find possible correlations between FFA, pancreatitis and lung injury using a rat model. AP was induced by intraductal infusion of two different concentrations of glycodeoxycholic acid (GDOC 17 mmol and 34 mmol). An equal number of animals had only cannulation of the pancreatic duct without infusion and served as controls (GDOC-control). In another experimental model iv.-infusion of oleic acid (OA) was used to create severe lung injury comparable to human ARDS. In this model control animals received iv.-infusion of saline solution only (SAL). At 2, 6, 12, 24 and 48 hours the animals were sacrificed and blood was collected for determination of FFA, amylase and pO2. The pancreas and lungs were removed for histologic examination and the lungs were weighed. GDOC-34 animals developed severe pancreatitis with hemorrhage and necrosis. Histology of the lungs showed edema, inflammatory infiltrates, hemorrhage and thickening of the alveolar membrane in GDOC-34 rats as well as in OA-animals. In contrast, there was only pancreatic edema until 24 hours in the GDOC 17 group and less severe histological changes in the lungs. Amylase, FFA, pO2 and lung weight were directly influenced by the different kinds of treatment. Furthermore, FFA correlated positively with the levels of amylase and lung weight and negatively with pO2. Infusion of OA alone also caused an increase in levels of amylase with pancreatic edema and focal necroses in some animals. These results show that it was possible to create different degrees of severity of AP which was in concordance with different degrees of morphologic changes and dysfunction in the lungs. FFA values correlated significantly with the clinical course as well as with increasing amylase, lung weight and decreasing pO2.

Acute Disease↗

PubMed1990

Hypocalcemia in experimental pancreatitis occurs independently of changes in serum nonesterified fatty acid levels.

Hypocalcemia and lipid abnormalities commonly occur in acute pancreatitis. Experimentally, increased plasma concentrations of free fatty acids (NEFA) can lower the serum calcium (Ca). We hypothesized that changes in blood-ionized calcium might parallel changes in NEFA concentration in pancreatitis. This hypothesis was tested in a model of severe necrotizing pancreatitis and a model of mild edematous pancreatitis. Adult male Sprague-Dawley rats (300-400 g) were randomized to receive: 100 microL sodium glycodeoxycholic acid (GDOC 34 mmol/L) infused into the pancreatic duct to produce severe necrotizing pancreatitis (Group 1); 100 microL 0.9% NaCl (NS) infused into the pancreatic duct (Group 2); Sham laparotomy (Group 3); A 6 h IV infusion of cerulein (5 mucg/kg/h) to produce mild edematous pancreatitis (Group 4); and a 6 h IV infusion of NS (Group 5). A significant time dependent decrease in blood-ionized Ca concentration, compared to normal rats, was observed in both GDOC-pancreatitis (0.836 +/- .057 vs 1.069 +/- .038 mmol/L p less than 0.001) and cerulein pancreatitis (0.988 +/- .028 vs 1.069 +/- .038 p less than 0.05), which was maximal 24 h after induction of pancreatitis. The degree of hypocalcemia correlated with the severity of pancreatitis (GDOC 0.836 +/- .057 vs cerulein 0.988 +/- .028 p less than .001). Hypocalcemia was not observed in any of the control groups. All experimental and control groups had significantly increased baseline NEFA concentrations compared with normal rats (p less than 0.001); however, no further increase in NEFA concentration occurred in conjunction with the observed time-dependent decline in ionized calcium concentrations. Although the NEFA concentrations observed in these experiments were comparable to those measured in human acute pancreatitis (exclusive of hyperlipemic pancreatitis), the time course of the changes suggests that increases in serum NEFA concentrations in experimental pancreatitis are not the primary factor mediating hypocalcemia.

Acute Disease↗

PubMed1992

A better model of acute pancreatitis for evaluating therapy.

Existing models of acute pancreatitis have limitations to studying novel therapy. Whereas some produce mild self-limited pancreatitis, others result in sudden necrotizing injury. The authors developed an improved model providing homogeneous moderately severe injury by superimposing secretory hyperstimulation on minimal intraductal bile acid exposure. Sprague-Dawley rats (n = 231) received low-pressure intraductal glycodeoxycholic acid (GDOC) at very low (5 or 10 mmol/L) concentrations followed by intravenous cerulein. Cerulein or GDOC alone caused only very mild inflammation. However, GDOC combined with cerulein was uniformly associated with more edema (p less than 0.0005), acinar necrosis (p less than 0.01), inflammation (p less than 0.006), and hemorrhage (p less than 0.01). Pancreatic injury was further increased and death was potentiated by increasing volume and duration of intraductal low-dose GDOC infusion. There was significant morphologic progression between 6 and 24 hours. The authors conclude that (1) combining minimal intraductal bile acid exposure with intravenous hyperstimulation produces homogeneous pancreatitis of intermediate severity that can be modulated at will; (2) the injury is progressive over at least 24 hours with finite mortality rate; (3) the model provides superior opportunity to study innovative therapy.

Acute Disease↗

PubMed2000

Isolation and characterization of a Lactobacillus amylovorus mutant depleted in conjugated bile salt hydrolase activity: relation between activity and bile salt resistance.

Growth experiments were conducted on Lactobacillus amylovorus DN-112 053 in batch culture, with or without pH regulation. Conjugated bile salt hydrolase (CBSH) activity was examined as a function of culture growth. The CBSH activity increased during growth but its course depended on bile salts type and culture conditions. A Lact. amylovorus mutant was isolated from the wild-type strain of Lact. amylovorus DN-112 053 after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. An agar plate assay was used to detect mutants without CBSH activity. In resting cell experiments, the strain showed reduced activity. Differences between growth parameters determined for wild-type and mutant strains were not detected. Comparative native gel electrophoresis followed by CBSH activity staining demonstrated the loss of proteins harbouring this activity in the mutant. Four protein bands corresponding to CBSH were observed in the wild-type strain but only one was detected in the mutant. The specific growth rate of the mutant strain was affected more by bile salts than the wild-type strain. Nevertheless, bile was more toxic for the wild-type strain. In viability studies in the presence of nutrients, it was demonstrated that glycodeoxycholic acid exerted a higher toxicity than taurodeoxycholic acid in a pH-dependent manner. No difference was apparent between the two strains. In the absence of nutrients, the wild-type strain died after 2 h whereas no effect was observed for the mutant. The de-energization experiments performed using the ionophores nigericin and valinomycin suggested that the chemical potential of protons (ZDeltapH) was involved in Lactobacillus bile salt resistance.

Amidohydrolases↗

PubMed2000

Effects of fructooligosaccharides and their monomeric components on bile salt resistance in three species of bifidobacteria.

The influence of fructooligosaccharides (FOS) and their monomeric components on bile salt resistance of Bifidobacterium breve ATCC 15700, Bif. longum ATCC 15707 and Bif. animalis ATCC 25527 was examined. The neosugars induced fructofuranosidase activities for the degradation of these saccharides. For the three strains tested the growth was identical and bile salts had the same inhibitory effect on growth whatever the carbohydrate used. The survival of Bif. breve and Bif. longum, in the presence of glycodeoxycholic acid depended, however, on carbohydrates: the toxic effects of the bile salt could be partly alleviated by the addition of a metabolizable C-source. For Bif. animalis, the presence of any carbohydrate in the incubation medium did not enhance the viability of the strain. But in the three deconjugating strains of bifidobacteria studied, the presence of neosugar during the growth led to improved resistance to the bactericidal effect of the bile salt compared with the monomeric components of these neosugars (glucose and fructose).

Animals↗

PubMed1981

Effect of bile acid derivatives on taurine biosynthesis and extracellular slime production in encapsulated Staphylococcus aureus S-7.

Various bile acids were added to cultures of encapsulated strains of Staphylococcus aureus growing in serum-soft agar medium of brain heart infusion broth. We examined effects of these compounds on cellular characteristics such as growth type, cell volume index, clumping factor reaction, slime yield, taurine content, and L-(--)-cysteic acid decarboxylase activity. Upon addition to the medium of either taurochenodeoxycholic acid, taurocholic acid (25 to 50 microgram/ml), or cholic acid (10 to 25 microgram/ml), the colonial morphology of taurine-positive cells (strain S-7) was altered from the diffuse to the compact type in serum-soft agar. Also, the titer of the clumping factor reaction increased, while the cell volume index and slime yield were markedly decreased. Tauro-bile acids, including taurocholic acid, taurochenodeoxycholic acid, taurodehydrocholic acid, and taurodeoxycholic acid (50 microgram/ml) inhibited the synthesis of taurine and resulted in decreased L-(--)-cysteic acid decarboxylase activity. Among all of the derivatives cholic acid itself was found to inhibit slime production and L-(--)-cysteic acid decarboxylase activity to the greatest extent. Glyco-bile acid derivatives and taurolicholic acid (50 to 100 microgram/ml) had no effect on L-(--)-cysteic acid decarboxylase activity. Compounds such as glycodeoxycholic acid (50 to 100 microgram/ml) had no effect upon any of the cellular characteristics tested. No effect was observed upon addition of any of these compounds to cultures of the taurine-negative strain (T-26-B). We did find a correlation between the inhibition of taurine biosynthesis and decreased slime production. Electron micrographs indicated that this encapsulated strain was converted to an unencapsulated state in the presence of bile acids.

Bile Acids and Salts↗

PubMed1985

Pancreatic duct and microvascular permeability to macromolecules. The relation to acute pancreatitis.

In a model of acute pancreatitis which requires that pancreatic enzymes leak from a permeable duct, we studied the role of intravenous enterokinase (195,000 daltons) in pancreatic enzyme activation. Anesthetized cats were given intravenous 16,16-dimethyl prostaglandin E2 to increase pancreatic blood flow and microvascular permeability. In some animals the permeability of the pancreatic duct was increased by perfusion of the duct with glycodeoxycholic acid (7.5 mM). Endogenous enzyme secretion was stimulated by IV CCK and secretin. Some cats also received enterokinase intravenously. Those animals that received PGE2, glycodeoxycholate, and enterokinase all developed pancreatitis. When any of these agents were not given the pancreases appeared normal. These findings were consistent with the hypothesis that intravenous enterokinase leaked from small pancreatic blood vessels into the pancreatic parenchyma and/or ducts where activation of pancreatic enzymes occurred. The development of pancreatitis appeared to require an increase in both microvascular and ductal permeability.

16,16-Dimethylprostaglandin E2↗

PubMed2000

Bile salt toxicity to some bifidobacteria strains: role of conjugated bile salt hydrolase and pH.

The purpose of this work was to study some aspects of bile salt toxicity towards bifidobacteria. A strain (Bifidobacterium coryneforme ATCC 25911) was selected for its lack of conjugated bile salt hydrolase activity (CBSH-), and was used with three deconjugating strains (CBSH+), for study of their growth and viability in the presence of two dihydroxylated conjugated bile salts (tauro- and glyco-deoxycholic acids). The presence of the glycoconjugate induced a more significant growth inhibition for the four strains than the tauroconjugate. The viability of the strains was measured at several pH levels. Glycodeoxycholic acid, but not taurodeoxycholic acid, exerted a lethal effect, which increased at low pH. This phenomenon was more pronounced for the CBSH- strain. We explain some of these results using an hypothesis based on the consequence of dissociation of conjugated and deconjugated bile salts, and the value of their pKa.

Amidohydrolases↗

PubMed1985

Effect of bile acids on the binding of drugs and dyes to human albumin.

Chenodeoxycholic, cholic, deoxycholic and taurodeoxycholic acids were found to inhibit the binding of 2-(4'-hydroxybenzeneazo)benzoic acid, methyl orange, sulphadimethoxine and warfarin to human albumin. In addition, glycodeoxycholic acid inhibited the binding of sulphadimethoxine and warfarin. In contrast, these bile acids did not inhibit the binding of phenylbutazone. The extent of displacement was in the rank order of: dihydroxy acids (chenodeoxycholic and deoxycholic) greater than trihydroxy acid (cholic) greater than conjugates (glycodeoxycholic and taurodeoxycholic). Thus the introduction of polar groups into the steroid nucleus of bile acids reduces their effectiveness as binding inhibitors. Displacement was usually accompanied by a decrease in the apparent association constant which suggests that the mechanism of displacement may be competitive.

Bile Acids and Salts↗

PubMed1999

The effects of calcium channel blocker and thyrotropin releasing hormone on acute necrotizing pancreatitis in rats.

The main purpose of this study was to investigate the influence of nimodipine, a calcium channel blocker (CCB) and thyroid-releasing hormone (TRH) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. CCB decreased blood pressure in rats in the control and pancreatitis groups. TRH corrected this decrease. CCB alone had no effect on PO2 serum amylase activity, calcium concentration, liver transaminases, lactate dehydrogenase or the degree of pancreatic damage, except for the serum concentration of creatinine. CCB+TRH reduced the concentrations of serum urea and creatinine, the degree of pancreatic damage, and increased PO2 and serum calcium concentration. CCB and CCB+TRH had no effect on pancreatic myeloperoxidase activity. CCB alone had no effect on the course of ANP, but CCB+TRH had beneficial effects on the course of the ANP and various systems.

Animals↗

PubMed2002

Glutathione depletion with L-buthionine-(S,R)-sulfoximine demonstrates deleterious effects in acute pancreatitis of the rat.

A common pathway in the pathogenesis of acute pancreatitis is the generation of free oxygen radicals. The most important defense mechanisms are free radical scavengers, especially glutathione. This study evaluates the influence of the inhibition of glutathione synthesis with L-buthionine-(S,R)-sulfoximine (BSO) on the course of experimentally induced acute pancreatitis in rats and the effects on isolated pancreatic acini and their secretion pattern. Thus acute necrotizing pancreatitis was induced with intraductal infusion of low-dose glycodeoxycholic acid and subsequent hyperstimulation with cerulein with and without pretreatment with BSO. In vitro pancreatic acini were isolated and stimulated with different concentrations of cerulein with and without BSO. The BSO-treated group showed a significantly reduced survival, more necrosis, and a decreased secretion of amylase in vivo. No effect on secretion pattern in either groups was seen in vitro and BSO did not exert toxic effects. Based on the data presented, this study demonstrates deleterious effects of scavenger depletion on the course of experimental pancreatitis. This is due to the systemic effects of free oxygen radicals rather than to local effects.

Acute Disease↗

PubMedDate not supplied

Effects of combined nutritional therapy on acute necrotizing pancreatitis in rats in the early phase of the disease.

The aim of this study was to investigate the influence of a small amount of enteral nutrition along with parenteral nutrition on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats in the early phase of disease. The induction of ANP resulted in a significant increase in mortality rate, intestinal permeability, bacterial infection in the pancreas and extrapancreatic organs, pancreatic necrosis and serum activity of urea and amylase, and a significant decrease in concentrations of calcium, protein and albumin. But no difference was observed between the pancreatitis groups. Significant hyperglycemia and increased liver transaminase activity were observed in rats treated with combined nutritional therapy (CNT). CNT did not improve the course of acute pancreatitis, intestinal permeability, bacterial translocation, or reduce the extent of acinar cell injury in ANP and is therefore unlikely to be of benefit in patients with pancreatitis in the early period.

Animals↗

PubMed1989

Pancreatic duct pressure, duct permeability and acute pancreatitis.

The relationship between pancreatic duct pressure, duct permeability to macromolecules and the development of acute pancreatitis was studied in a cat model. Perfusion of the pancreatic duct with 15 mM glycodeoxycholic acid, ethanol administration, or secretagogue-stimulated pancreatic secretion against greater than 50 per cent duct obstruction resulted in an increase in peak pancreatic duct pressure in all animals. Duct permeability to 20,000 molecular weight dextran molecules was increased in 22 of 29 experimental animals compared with two of 22 control animals (P less than 0.01). Perfusion of the pancreatic duct with activated pancreatic enzymes resulted in acute pancreatitis in 24 of 29 experimental animals compared with three of 22 control animals (P less than 0.01). These results suggest that pancreatic ductal hypertension, resulting in increased ductal permeability to large molecules, may be a common early event in gallstone and alcoholic pancreatitis.

Acute Disease↗