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Results for “Glycodeoxycholic Acid”

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PubMed1995

Nuclear serine protease activity contributes to bile acid-induced apoptosis in hepatocytes.

Glycodeoxycholate (GDC) induces apoptosis in hepatocytes by a mechanism associated with DNA cleavage by endonucleases. In many models of apoptosis, proteolysis is required prior to DNA cleavage. Our aims were to determine if enhanced proteolysis is a mechanism causing GDC-mediated apoptosis. In cultured rat hepatocytes exposed to 50 microM GDC for 4 h, nonlysosomal proteolysis increased by 65% compared with controls. The serine protease inhibitor N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK; 100 microM) reduced cell death from apoptosis by 75% after 4 h of treatment with GDC. TLCK also inhibited DNA fragmentation. There was a twofold increase in nuclear serinelike protease activity during GDC-induced apoptosis accompanied by a 2.5-fold reduction in nonnuclear serine protease activity, suggesting translocation of the protease from the cytosol to the nucleus. Zn2+, an inhibitor of apoptosis, also inhibited nonlysosomal proteolysis and nuclear serinelike protease activity. These novel data suggest that nonlysosomal serinelike protease activity contributes to hepatocyte apoptosis. These data may be important in understanding apoptosis in other cell types and in providing insight into the mechanisms of liver injury during cholestasis.

Animals↗

PubMed1984

Mitotic aneuploidy as a possible mechanism for tumour promoting activity in bile acids.

A range of conjugated and free bile acids were assayed for their ability to induce a variety of genetic endpoints in growing cells of yeast. None of the bile acids showed any activity in assays for the induction of mitotic crossing-over and mutation whereas the free bile acids lithocholic, chenodeoxycholic, deoxycholic and cholic acid were potent inducers of mitotic chromosome aneuploidy. In contrast, both conjugated bile acids, taurodeoxycholic and glycodeoxycholic lacked the ability to induce mitotic aneuploidy. When the potency of the free bile acids were compared, lithocholic and chenodeoxycholic acids showed higher levels of induction of mitotic aneuploidy per lethal event compared with cholic and deoxycholic acids. In view of the previously observed correlation between the ability of a chemical to induce chromosome aneuploidy and tumour promotional activity, the results indicate that the levels of free bile acids in the colon may be significant factors in the etiology of colonic cancer.

Aneuploidy↗

PubMed1989

The nature of choleresis induced by deoxycholate and its conjugates in the rabbit.

A hypothesis for the mechanism of bile salt-induced choleresis with increased bile bicarbonate concentration (cholehepatic recycling; CHR), requires a relatively high pK'a value of a bile salt to be easily protonated in bile canaliculi. If the choleresis induced by taurodeoxycholate and glycodeoxycholate (which increase bile bicarbonate concentration in rabbits) is to be explained by this thesis, these bile salts must be extensively deconjugated in the liver, enabling a bile salt having a higher pK'a value, free deoxycholate, to undergo CHR. With a stepwise increase in the infusion rate, the increments of bicarbonate concentration, as well as the bile flow rate induced by taurodeoxycholate and glycodeoxycholate, were as efficient as those caused by an equimolar infusion of deoxycholate. With infusion of conjugated deoxycholates, the major bile salts excreted in the bile were those which had been infused. In studies with conjugated deoxycholates, unconjugated deoxycholate was not detectable in the bile. Furthermore, deoxycholate concentration in the liver significantly increased after a 2-h infusion of deoxycholate but did not increase after infusion of either glycodeoxycholate or taurodeoxycholate. The present results suggest that the choleresis induced by conjugated deoxycholates in rabbits requires an explanation other than CHR of deoxycholate.

Animals↗

PubMed1981

Effect of glucose on jejunal water and solute absorption in the presence of glycodeoxycholate and oleate in man.

Jejunal perfusion studies were performed in 12 healthy volunteers to study the effects of 14 and 56 mM glucose on fluid secretion induced by 5 mM glycodeoxycholate on 7 mM oleate. Glucose enhanced water absorption under control conditions and reduced water secretion induced by glycodeoxycholate or oleate (P less than 0.01). As has been observed previously, glycodeoxycholate and oleate inhibited glucose absorption (P less than 0.001) and significant linear relationships existed between net water movement and glucose absorption. Glycodeoxycholate also reduced the absorption of 14 mM arabinose (P less than 0.05) and oleate reduced the absorption of 56 mM mannitol (P less than 0.05). Reduced solute absorption in the presence of glycodeoxycholate and oleate, therefore, cannot be attributed to an effect on active transport alone. The relationships between sodium transport and water absorption varied with the glucose concentration in the perfusion solutions. Similarly, the relationships between glucose absorption and sodium absorption varied with glucose concentration. The data suggest that a significant amount of glucose can be absorbed without concomitant absorption of sodium. The data indicate that glucose absorption can stimulate water absorption directly without the mediation of sodium and that water movement follows glucose at a rate which maintains isotonicity.

Arabinose↗

PubMed1986

Effects of bile salts on bile formation in rabbits.

The effects of different species of bile salts: deoxycholate, taurochenodeoxycholate, ursodeoxycholate, glycodeoxycholate, tauroursodeoxycholate, chenodeoxycholate and cholate (DCA, TCDC, UDCA, GDCA, TUDC, CDCA, CA) on bile secretion were examined in anesthetized rabbits using two different infusion routes. When bile salts were infused intravenously, all bile salts (except for TCDC) significantly increased the volume of bile and bile salt excretion, but their respective efficiency for bile formation was different. The concentration of bicarbonate ion in the bile significantly increased during the choleretic periods induced by DCA, UDCA, GDCA and CDCA but remained unchanged with the other bile salts (CA, TCDC, TUDC). In rabbits, where a bile salt solution was infused in the duodenum and then drained from the intestine through an incision in the distal part of duodenum, none of these bile salts affected bile secretion. The effects of intravenously administered bile salts on rabbit bile secretion are different in terms of their choleretic potency and bicarbonate excretion depending on the species of bile salts used. Furthermore, it was concluded that the intraduodenal infusion of UDCA, which was found to stimulate the pancreatic exocrine function, did not affect bile secretion.

Animals↗

PubMed1978

Light-scattering studies on bile acid salts II: pattern of self-association of sodium deoxycholate, sodium taurodeoxycholate, and sodium glycodeoxycholate in aqueous electrolyte solutions.

The pattern of self-association of the bile salts sodium deoxycholate, sodium glycodeoxycholate, and sodium taurodeoxycholate was investigated in aqueous electrolyte solutions by the light-scattering technique. The turbidity of the bile salt solutions was obtained over the concentration range of 0-20 mg/ml at 25 degrees. These data were analyzed according to a monomer-micellar equilibrium model and a stepwise association model. Comparison of the light-scattering data with these models suggests that the monomer-micellar model may be inappropriate. Analysis of the data according to the stepwise association model suggests that the dihydroxy bile salts associate to form dimers, trimers, and tetramers in addition to a larger aggregate which varies in size depending on the degree of conjugation of the bile salt.

Chemical Phenomena↗

PubMed2000

Permeation of sumatriptan through human vaginal and buccal mucosa.

Continued interest in the various routes by which sumatriptan may be administered prompted us to investigate its passage through buccal mucosa. Because human buccal mucosa is scarce, we proposed using the relatively abundant vaginal mucosa, which has been shown to have comparable diffusion rates for a number of widely varying molecules, as a model of buccal mucosa. In addition, by comparing these two tissues with respect to their permeability to sumatriptan, the human vaginal/buccal mucosa model could be further evaluated. Clinically healthy human vaginal and buccal mucosa specimens were used in the permeability studies. Permeability to sumatriptan was determined using a continuous flow-through diffusion system in the presence and absence of permeation enhancers. No statistically significant differences in permeability could be demonstrated for both mucosae toward sumatriptan. Flux values obtained in the absence and presence of glycodeoxycholate and lauric acid (1:1 molar ratio) to sumatriptan of buccal and vaginal mucosa, respectively, were not significantly different. The results obtained further support the hypothesis of the vaginal/buccal mucosal in vitro permeability model and suggest that this model may be used in conjunction with various absorption enhancers. Further studies on the buccal route of absorption of sumatriptan are thus warranted.

Administration, Buccal↗

PubMed1995

Purification and Characterization of Conjugated Bile Salt Hydrolase from Bifidobacterium longum BB536.

Bifidobacterium species deconjugate taurocholic, taurodeoxycholic, taurochenodeoxycholic, glycocholic, glycodeoxycholic, and glycochenodeoxycholic acids. The enzyme level increases in the growth phase. No increase in activity is observed for the cytoplasmic enzyme after addition of conjugated bile acids to a stationary-phase culture. Conjugated bile salt hydrolase (BSH) was purified from Bifidobacterium longum BB536. Its apparent molecular mass in denaturing polyacrylamide gel electrophoresis was ca. 40,000 Da. The intact enzyme had a relative molecular weight of ca. 250,000 as determined by gel filtration chromatography, suggesting that the native BSH of B. longum is probably a hexamer. The purified enzyme is active towards both glycine and taurine conjugates of cholate, deoxycholate, and chenodeoxycholate. The pH optimum is in the range of 5.5 to 6.5. A loss of BSH activity is observed after incubation at temperatures higher than 42(deg)C; at 60(deg)C, 50% of the BSH activity is lost. The importance of free sulfhydryl groups at the enzyme active center is suggested. For B. longum BB536, no significant difference in the initial rate of deconjugation and enzymatic efficiency appears between bile salts. The enzymatic efficiency is higher for B. longum BB536 than for other genera. In this paper, a new method which permits a display of BSH activity directly on polyacrylamide gels is described; this method confirms the molecular weight obtained for B. longum BB536 BSH.

Journal Article↗

PubMedDate not supplied

[Bile acids in the bile in diabetes mellitus].

Hepatic and gall bladder bile of healthy persons (8) and of patients with severe form of diabetes mellitus (17) was studied. Paer chromatography was applied for determination of cholic, chenodeoxycholic, deoxycholic bile acids and their conjugates with glycin and taurine. An absolute content and percentage of glycodeoxycholic and glycochenodeoxycholic bile acids were increased, and glycochenodeoxycholic acid content and taurates proportion were decreased in the gall bladder and hepatic bile of diabetic patients. The data obtained pointed to disturbed hepatic function in severe diabetes mellitus; it was expressed in suppression of bile acids synthesis and conjugation, and also in depression of transformation of deoxycholic into cholic acid.

Adult↗

PubMed2004

Noninvasive methods to determine the critical micelle concentration of some bile acid salts.

In this work the critical micelle concentrations (cmc) of four bile salts, sodium cholate, sodium glycocholate, sodium deoxycholate, and sodium glycodeoxycholate, are determined and presented. Three independent noninvasive methodologies (potentiometry, derivative spectrophotometry, and light scattering) were used for cmc determination, at 25 degrees C with ionic strength adjusted to 0.10 M with NaCl. Spectrophotometric and potentiometric studies of some bile salts were also executed at various ionic strength values, thus allowing the influence of the ionic strength on the cmc value of the bile salt to be assessed. A critical comparison of the cmc values obtained with data collected from the literature is presented. Furthermore, this work makes an evaluation of the conceptual bases of different methodologies commonly used for cmc determination, since variations in the results obtained can be related mainly to different intrinsic features of the methods used (such as sensitivity or the need to include tracers or probes) or to the operational cmc definition applied. The undoubted definition of the experimental bile salt concentration that corresponds to cmc (operational cmc) is essential since in the case of these amphiphiles the formation of micelles is not as abrupt as in the case of ordinary association colloids. The biphasic nature of their aggregation leads to a "round-shaped" variation of the experimental parameters under analysis, which makes difficult the evaluation of the cmc values and can be responsible for the different results obtained.

Bile Acids and Salts↗

PubMed1979

Glycodeoxycholate transport in brush border membrane vesicles isolated from rat jejunum and ileum.

The transport of the bile salt, glycodeoxycholate, was studied in vesicles derived from rat jejunal and ileal brush border membranes using a rapid filtration technique. The uptake was osmotically sensitive, linearly related to membrane protein and resembled D-glucose transport. In ileal, but not jejunal, vesicles glycodeoxycholate uptake showed a transient vesicle/medium ratio greater than 1 in the presence of an initial sodium gradient. The differences between glycodeoxycholate uptake in the presence and absence of a Na+ gradient yielded a saturable transport component. Kinetic analysis revealed a Km value similar to that described previously in everted whole intestinal segments and epithelial cells isolated from the ileum. These findings support the existence of a transport system in the brush border membrane that: (1) reflects kinetics and characteristics of bile salt transport in intact intestinal preparations, and (2) catalyzes the co-transport of Na+ and bile salt across the ileal membrane in a manner analogous to D-glucose transport.

Animals↗

PubMed2002

Effects of bile acids on dog pancreatic duct epithelial cell secretion and monolayer resistance.

Pancreatic duct epithelial cells (PDEC) mediate the secretion of fluid and electrolytes and are exposed to refluxed bile. In nontransformed cultured dog PDEC, which express many ion transport pathways of PDEC, 1 mM taurodeoxycholic acid (TDCA) stimulated an (125)I(-) efflux inhibited by DIDS and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and a (86)Rb(+) efflux inhibited by charybdotoxin. Inhibition by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM suggests mediation via increased intracellular Ca(2+) concentration, whereas the absence of lactate dehydrogenase release excludes cellular toxicity. At 1 mM, TDCA stimulated a larger (125)I(-) efflux than glycodeoxycholate; two dihydroxy bile acids, taurochenodeoxycholate and TDCA, were similarly effective, whereas a trihydroxy bile acid, taurocholate, was ineffective. In Ussing chambers, 1 mM serosal or 2 mM luminal TDCA stimulated an I(sc) increase from confluent PDEC monolayers. TDCA also stimulated 1) a short-circuit current (I(sc)) increase from basolaterally permeabilized PDEC subject to a serosal-to-luminal Cl(-) gradient that was inhibited by BAPTA-AM, DIDS, and NPPB and 2) an I(sc) increase from apically permeabilized PDEC subject to a luminal-to-serosal K(+) gradient inhibited by BAPTA-AM and charybdotoxin. Along with the efflux studies, these findings suggest that TDCA interacts directly with PDEC to stimulate Ca(2+)-activated apical Cl(-) channels and basolateral K(+) channels. Monolayer transepithelial resistance was only minimally affected by 1 mM serosal and 2 mM luminal TDCA but decreased after exposure to higher TDCA concentrations (2 mM serosal and 4 mM luminal). A secretory role for bile acids should be considered in pancreatic diseases associated with bile reflux.

Animals↗

PubMedDate not supplied

Application of structural descriptors for the evaluation of some physicochemical properties of selected bile acids.

Selected bile acids such as: cholic (C), glycocholic (GC), glycodeoxycholic (GDC), chenodeoxycholic (CDC), deoxycholic (DC), lithocholic (LC) and glycolithocholic acids (GLC) were separated by TLC technique. Selected topological indices, based on adjacency and distance matrices, and electrotopological states were calculated for the studied bile acids. Different possibilities of application of structural descriptors to calculate specified physicochemical data of the examined bile acids were found (QSPR). Usability of structural descriptors for the estimation of chromatographic separations of the examined bile acids was shown only for optimal separation conditions. Of all topological indices, only the index C allows to describe the order of adsorption of the examined bile acids (QSRR). Whereas, Gutman's index Mv was proved to be most useful for the estimation of lipophilicity of the examined bile acids (QSAR). The studies indicate that the range of applicability of given structural descriptors is limited for certain analytical and physicochemical problems.

Bile Acids and Salts↗

PubMed1984

Effects of bile salts on permeability and morphology of main pancreatic duct in cats.

We studied the changes in permeability and morphology in the main pancreatic duct of cats after exposure of the duct to specific bile salts. Cats were anesthetized and the main pancreatic duct was cannulated in the tail and head of the pancreas. The duct was perfused with sodium cholate (1, 1.5, 2, 15 mM) or sodium glycodeoxycholate (1, 2, 15 mM) for 60 min at pressures which never exceeded 20 cm water. Then the duct was perfused with fluorescein-tagged dextran molecules of specific size (3000, 20,000, or 40,000 daltons). Recovery of the dextran from portal venous blood indicated that the duct was permeable to that particular dextran. Normally the ducts were impermeable to even the 3000-dalton dextran, and perfusion with either 1 mM cholate or glycodeoxycholate did not change this. However, perfusion with either bile salt at concentrations above 1 mM progressively increased duct permeability. At this highest bile salt concentrations used, the ducts became permeable to molecules as large as 20,000 daltons. Morphologic changes paralleled the changes in permeability. Control animals had pancreatic ducts whose ultrastructure was indistinguishable from normal. Perfusion of the ducts with low concentrations of bile salt for up to 60 min resulted only in a loss of microvilli from the cell surface and an increase in cytoplasmic phagolysosomes. Perfusion with higher concentrations of bile salt for 5-60 min induced progressively severe alterations. These included disruption of the tight junctions and the swelling of intercellular spaces between the duct cells, flattening of the duct epithelium, and eventual cell loss which left a break in the epithelial lining of the duct. These studies indicate that the pancreatic duct in cats, exposed to specific bile salts at physiological concentrations and pressures, undergoes marked structural alterations. The duct becomes permeable to molecules at least as large as 20,000 daltons, whereas it is normally impermeable to molecules as small as 3000 daltons.

Animals↗

PubMed1986

Bile salt dependent bile flow in the rabbit: evidence for the importance of an amiloride inhibitable pathway.

Bile salt dependent flow and electrolyte secretion in response to two bile salts were studied in awake rabbits. It was found that sodium glycodeoxycholate had a much greater choleretic and cholioneretic efficiency than sodium taurocholate. The effect of the bile salts on flow and electrolyte secretion was not linear across the range of bile salt secretion rates studied. When amiloride was administered significant decreases in choleretic and cholioneretic efficiencies occurred, but furosemide had no effect. It is concluded that bile salts stimulate electrolyte transport via amiloride inhibitable cellular processes, and that this electrolyte transport is in part responsible for bile salt dependent bile flow.

Amiloride↗

PubMed1985

Heterogeneity of rabbit hepatocytes for bile secretion after acinar zone 3 damage induced by bromobenzene. Effect of bilirubin and bile salt infusions.

Anaesthetized rabbits were used to study the effect of bromobenzene-induced hepatic damage to the acinar zone 3 on bile flow, bile salt, sodium secretion as well as bilirubin transport in basal conditions or with infusion of sodium glycodeoxycholate. The bromobenzene-pretreated animals exhibited in basal conditions a lower bile flow (44%) than that of the controls, with a smaller decrease in bile salt output (27%) and sodium output (29%), whereas no modification in endogenous bilirubin excretion was observed. The bile salt independent fraction of secretion (BSIF) was reduced significantly after the toxic lesion both in terms of absolute and relative values. The hepatocytes of the periportal zone were capable of excreting the totality of bilirubin presented to the liver, regardless of the extent of bile flow or the input of bile salts. The infusion of bilirubin at 1.0 mumole/kg/min led to a fall in bile flow which was attributed to the interference of the pigment with the BSIF. The maximal bilirubin excretion was significantly smaller in bromobenzene-pretreated animals than in the controls, which could be due to the incapacity of the intoxicated rabbits to recruit quiescent hepatocytes. When glycodeoxycholate was administered under conditions of maximal bilirubin transport, bile flow increased as did bile salt secretion in both controls and animals with damaged livers. However, clear differences persisted between the two, which could be attributed not only to the volume fraction of necrosis but also to an interference by bilirubin with the hepatic handling of bile salts. Maximal bilirubin excretion increased in a similar way in both groups after glycodeoxycholate administration. It is proposed that glycodeoxycholate infusion facilitates the hepatic depletion of bilirubin, probably by stimulating transport processes.

Animals↗

PubMed1998

Changes of lipid metabolism in plasma, liver and bile during cholesterol gallstone formation in rabbit model.

AIM:To find out the relationship between the disturbances of lipid metabolism and the formation of cholesterol gallstones by studying the changes of lipid metabolism in plasma, liver tissue and the bile.METHODS:Male and female white Japanese rabbits were divided randomly into a control group (Con) and four experimental groups of 10 rabbits each fed with a diet containing 1.2% cholesterol for one, two, three and four weeks (1wk, 2wk, 3wk and 4wk group). The measurement of plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and its subfractions (HDL(2)-C, HDL(3)-C), very low and low density lipoprotein cholesterol (VLDL-C, LDL-C) was taken with standard enzymatic techniques. Apolipoprotein (apo) concentrations in plasma were measured by radial immunodiffusion assay for apoA1, apoB100, aopCII and apoC . Total cholesterol of liver was measured by the enzymatic procedure for each animal.Bile acids, mainly glycocholate (GCA) and glycodeoxycholate (GDCA) were detected by dual wavelength thin layer scanner.RESULTS:In all the experimental groups fed with dietary cholesterol, cholesterol crystal was found in the gallbladder in 2/10 cases of the 1wk group, 4/10 of the 2wk group,6/10 of the 3wk group and 7/10 of the 4wk group respectively. The concentration of plasma total cholesterol (TC),triglyceride (TG), phospholipid (pl), VLDL-C, LDL-C, apoB100, apoCII, apoC gradually increased (P < 0.05)with the prolonged feeding time of dietary cholesterol. High density lipoprotein cholesterol and its subfractions (HDL(2)-C, HDL(3)-C) showed a tendency to decrease, but without statistical significance (P > 0.05). ApoA1 was reduced with increased feeding time of dietary cholesterol (P < 0.05).The hepatic and biliary cholesterol increased 1-1.5 times as compared with the control group (t =5.221 and 3.445, P < 0.05).The GCA gradually decreased beginning from the control group to the 4wk group (P <0.05).CONCLUSION:Owing to the high cholesterol diet, the increased concentrations of plasma TC, TG, VLDL-C, LDL-C, hepatic TC and TG, apoB100, apoCII and apoC possibly enhanced the secretion of biliary cholesterol into bile; the decreased plasma apoA1 level might reduce the secretion of antinucleating factor into bile.All those factors mentioned above probably contribute to the formation of cholesterol gallstones.

Journal Article↗

PubMed1990

[Excretion of bile acids in feces in pathology of the liver and intestines].

Intestinal excretion of free bile acids (BA), i.e. of cholic, chenodeoxycholic, deoxycholic, lithocholic, and of conjugated BA, i.e. of glycocholic, glycodeoxycholic together with glycochenodeoxycholic, taurocholic, taurodeoxycholic together with taurochenodeoxycholic acids, was examined in patients with viral hepatitides (VH), chronic hepatitis (CH), biliary cirrhosis of the liver (BCL), and acute dysentery (AD), as were the effects of therapy on these acid levels. The findings evidence that fecal levels of free BA are significantly reduced during the acute period of VH, CH, AD, and BCL, whereas the levels of conjugated acids are elevated in all the examinees except the BCL patients, in whom these acids are unchanged. Study of BA excretion in VH patients treated with prednisolone has demonstrated a normalizing effect of this therapy on the spectrum of excreted free BA. Furazolidone and erythromycin therapy resulted in disordered transformation of 'primary' BA into 'secondary' ones and to deconjugation of BA, this being possibly related to these drugs effects on intestinal microflora.

Bile Acids and Salts↗