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Willy Verstraete - One of the best experts on this subject based on the ideXlab platform.

  • Protective effect of the Bile Salt hydrolase-active Lactobacillus reuteri against Bile Salt cytotoxicity.
    Applied microbiology and biotechnology, 2000
    Co-Authors: P. De Boever, R. Wouters, L. Verschaeve, P. Berckmans, Greet Schoeters, Willy Verstraete
    Abstract:

    Bacterial Bile Salt hydrolysis is considered a risk factor for the development of colon cancer because of the risk of forming harmful secondary Bile Salts after an initial deconjugation step. In this study, the influence of enhanced bacterial Bile Salt transformation by the Bile Salt hydrolase-active Lactobacillus reuteri was studied in batch culture using the microbial suspension of the Simulator of the Human Intestinal Microbial Ecosystem; (SHIME), which was supplemented with oxgall at 5 g/l or 30 g/l. Changes in the fermentative capacity of the microbial ecosystem and the (geno)toxic properties of the SHIME supernatants were investigated. Increasing concentrations of oxgall inhibited the fermentation. Transient cell toxicity was observed for samples supplemented with 5 g oxgall/l, while samples with 30 g oxgall/l exhibited toxicity. The results of the haemolysis test suggest that the detrimental effects were probably due to the membrane-damaging effects of Bile Salts. In all cases, the adverse effects could be counteracted by the addition of 7.5 +/- 0.5 log10 CFU L. reuteri/ml. Plausible mechanisms for the protective properties of L. reuteri could involve a precipitation of the deconjugated Bile Salts and a physical binding of Bile Salts by the bacterium, thereby making the harmful Bile Salts less bioavailable.

Timothy S. Wiedmann - One of the best experts on this subject based on the ideXlab platform.

  • Examination of the solubilization of drugs by Bile Salt micelles
    Journal of pharmaceutical sciences, 2002
    Co-Authors: Timothy S. Wiedmann, Lamya Kamel
    Abstract:

    The purpose of this review is to provide a critical examination of the reported solubilization of drugs by Bile Salt micelles. The underlying premise is that with better information regarding the inherent biological complexity, efforts to predict the oral bioavailability of drug will be enhanced. The common means of comparing the reported values was chosen to be the solubilization ratio. This is equal to the moles of drug solubilized per mole of Bile Salt. The values were segregated according to Bile Salt type, temperature, ionic strength, and the presence and absence of added lipids. Only segregation by Bile Salt type was pairwise statistically significant. From the solubilization ratios and the reported values of the aqueous solubility, the logarithms of the mole fraction micelle partition coefficients, log K(m/a), were calculated. The log K(m/w) was found to be correlated with the reported logarithm of the octanol/water partition coefficient. The rank order of slopes of the log K(m/a) as a function of log K(o/w) was cholate approximately taurodeoxycholate > glycocholate approximately taurocholate approximately glycodeoxycholate, with deoxycholate not being statistically different from the other data sets. The slope and intercept for the Bile Salt mixed micelle systems were 0.600 and 2.44, respectively, which were statistically indistinguishable from glycocholate, taurocholate, and glycodeoxycholate Bile Salt data. The existence of statistically significant correlations suggests that predicting the solubilization in the intestine may be possible with in vitro measurements if additional information is gathered in the appropriate micellar solutions.

  • Spectral properties and ionization behavior of retinoids, II.: Bile Salt solutions
    International Journal of Pharmaceutics, 1998
    Co-Authors: Chien Hsuan Han, Cheryl L. Zimmerman, Timothy S. Wiedmann
    Abstract:

    Abstract Purpose: The spectral properties and ionization behavior of retinoic acid (RA) and three structurally related arotinoids, MTTO, TTNPB, and TTNN, have been determined in simple micellar and mixed micellar solutions to provide a better understanding of the intestinal absorption of retinoids. Methods: Spectrophotometric and pH measurements have been made to determine the ionization constant in Bile Salt solutions. The fluorescent intensity and polarization of TTNN was determined. The extent of solubilization of retinoic acid in 10 mM NaTC/10 mM egg PC solutions was determined as a function of pH. Results: The rank order of wavelengths of maximum absorption, λ max , was as follows: aqueous solution>dihydroxy Bile Salt>trihydroxy Bile Salt>ethanol>mixed micelles. The interaction as reflected in the λ max of arotinoids with the Bile Salts at low pH depended on the mixing order, but this was not the case for retinoic acid. The rank order of the observed negative logarithm of the ionization constants, p K a obs , was aqueous solution>mixed micelles>dihydroxy Bile Salt>trihydroxy Bile Salt which reflects both the polarity as well as the electrostatic charge of the aggregates. The calculated electrostatic and dielectric effects on the ionization constant were comparable in Bile Salt micelles suggesting that TTNN is repositioned with a change in the ionic strength and that the size distribution of Bile Salt simple micelles appears to be perturbed by the presence of TTNN. In addition, the size of the Bile Salt-TTNN aggregate was independent of ionic strength and the type of Bile Salt. The solubilization of retinoic acid in Bile Salt/egg PC mixed micelle does not follow the expected dependence of pH indicating the presence of specific interactions. Conclusions: Retinoic acid and its derivatives exist almost exclusively in aggregated forms with RA forming a distinct type of aggregate in comparison to the arotinoids. The values of the p K a obs of the retinoids ranged from near 5 in simple Bile Salt aggregates to >7 in self-associated aggregates and mixed micelles which reflects the sensitivity of the ionization to the environment. This sensitivity has direct implications for the extent solubilized in the intestine and thereby complicates efforts at understanding the mechanism of the oral absorption of retinoids.

  • Concentration-Dependent Diffusion of Bile Salt/Phospholipid Aggregates
    The Journal of Physical Chemistry, 1996
    Co-Authors: Timothy S. Wiedmann
    Abstract:

    Bile Salt/phospholipid aggregates are present as concentrated, anionic colloids in the gallbladder. After mixing with dietary lipids, these aggregates diffuse through the hydrated, negatively charged glycoprotein network at the intestinal surface prior to absorption. Analysis of these complicated processes requires a characterization of the lipid aggregate as well as its diffusion. Moreover, the excluded-volume effects on the lipid aggregate diffusion need to be addressed. Thus, the diffusion coefficients of Bile Salt, phospholipid, and water were obtained from four series of lipid dilutions by a Fourier transform pulsed-field gradient spin-echo 1H NMR diffusion method. Dialysis experiments were performed to provide an independent estimate of the intermicellar concentration. Four lipid solutions with different total phospholipid/Bile Salt ratios were then diluted with Bile Salt solutions containing the approximate intermicellar concentration. With these four series of solutions, the isopotential specific ...

Birgitta Strandvik - One of the best experts on this subject based on the ideXlab platform.

  • Bile Salt sulphotransferase activity in the liver of cholestatic infants
    Scandinavian journal of clinical and laboratory investigation, 1994
    Co-Authors: K. Obinata, A. Nemeth, Åke Ellin, Birgitta Strandvik
    Abstract:

    Obinata K, Nemeth A, Ellin A, Strandvik B. Bile Salt sulphotransferase activity in the liver of cholestatic infants. Scand J Clin Lab Invest 1994; 54: 285-90.A simple assay of Bile Salt sulphotransferase activity in human liver was developed. The system used glycolithocholate and PAPS as substrates. Km values for glycolithocholate and PAPS were 2.8 μM and 11.5 μM, respectively. Furthermore Bile Salt sulphation capacity in infants with cholestasis was investigated by measuring the activity of the Bile Salt sulphotransferase in the liver. No significant difference was found between the sulphotransferase activity in cholestatic infants and non-cholestatic adults. In addition the magnitude of the Bile Salt sulphotransferase activity in as neonatal liver did not differ from the enzymatic activity in adult liver. It is thus considered unlikely that low degree of sulphation of Bile Salts in infants is due to reduced capacity of this enzyme system.

I Mierau - One of the best experts on this subject based on the ideXlab platform.

  • screening of lactic acid bacteria for Bile Salt hydrolase activity
    Journal of Dairy Science, 1999
    Co-Authors: H Tanaka, K Doesburg, T Iwasaki, I Mierau
    Abstract:

    Abstract Bile Salt hydrolysis is an important metabolic reaction in the Bile Salt metabolism of mammals. This reaction has a facilitating effect for Bile Salt excretion but can also be involved in various illnesses. In recent years interest has increased to use Bile Salt hydrolysis to influence the cholesterol metabolism of humans and farm animals. To understand the distribution and range of Bile Salt hydrolase activity in lactic acid bacteria, we screened more than 300 strains of the genera Bifidobacterium and Lactobacillus and the species Lactococcus lactis, Leuconostoc mesenteroides , and Streptococcus thermophilus . Results obtained for 273 strains showed that Bile Salt hydrolase activity is common in Bifidobacterium and Lactobacillus but absent in L. lactis, Leu. mesenteroides , and S. thermophilus . Nearly all bifidobacteria species and strains have Bile Salt hydrolase activity, whereas this activity can only be found in selected species of lactobacilli. A strong correlation can be observed between the habitat of a genus or species and the presence of Bile Salt hydrolase activity. Most often Bile Salt hydrolase activity is found in strains that have been isolated from the intestines or from feces from mammals—an environment rich in conjugated and unconjugated Bile acids. Strains and species from other habitats like milk or vegetables—environments from which Bile Salts are absent—do normally not have Bile Salt hydrolase activity. In two independent assays, we established that Bile Salt hydrolase activity in bifidobacteria is, in general, much higher than in lactobacilli.

Bruno Stieger - One of the best experts on this subject based on the ideXlab platform.

  • Bile Salt Transporters
    Drug Transporters: Molecular Characterization and Role in Drug Disposition: Second Edition, 2014
    Co-Authors: Jyrki J Eloranta, Bruno Stieger, Gerd-achim Kullak-ublick
    Abstract:

    Bile Salts are the major organic solutes in Bile and undergo extensive enterohepatic circulation. Hepatocellular Bile Salt uptake is mediated predominantly by the Na+-taurocholate cotransport proteins Ntcp (rodents) and NTCP (humans) and by the Na+-independent organic anion-transporting polypeptides Oatp1, Oatp2, and Oatp4 (rodents) and OATP-C (humans). After diffusion (bound by intracellular Bile Salt–binding proteins) to the canalicular membrane, monoanionic Bile Salts are secreted into Bile canaliculi by the Bile Salt export pump Bsep (rodents) or BSEP (humans). Both belong to the ATP-binding cassette (ABC) transporter superfamily. Dianionic conjugated Bile Salts are secreted into Bile by the multidrugresistance-associated proteins Mrp2/MRP2. In Bile ductules, a minor portion of protonated Bile acids and monomeric Bile Salts are reabsorbed by non-ionic diffusion and the apical sodium-dependent Bile Salt transporter Asbt/ASBT, transported back into the periductular capillary plexus by Mrp3/MRP3 [and/or a truncated form of Asbt (tAsbt)], and subjected to cholehepatic shunting. The major portion of biliary Bile Salts is aggregated into mixed micelles and transported into the intestine, where they are reabsorbed by apical Oatp3, the apical sodium-dependent Bile Salt transporter (ASBT), cytosolic intestinal Bile acid-binding protein (IBABP), and basolateral Mrp3/MRP3 and tAsbt. Transcriptional and posttranscriptional regulation of these enterohepatic Bile Salt transporters is closely related to the regulation of lipid and cholesterol homeostasis. Furthermore, defective expression and function of Bile Salt transporters have been recognized as important causes for various cholestatic liver diseases

  • Enterohepatic Bile Salt Transporters in Normal Physiology and Liver Disease
    Gastroenterology, 2004
    Co-Authors: Gerd-achim Kullak-ublick, Bruno Stieger, Peter J. Meier
    Abstract:

    The vectorial transport of Bile Salts from blood into Bile is essential for the generation of Bile flow, solubilization of cholesterol in Bile, and emulsification of lipids in the intestine. Major transport proteins involved in the enterohepatic circulation of Bile Salts include the hepatocellular Bile Salt export pump (BSEP, ABCB11), the apical sodium-dependent Bile Salt transporter (ASBT, SLC10A2) in cholangiocytes and enterocytes, the sodium-dependent hepatocyte Bile Salt uptake system NTCP (SLC10A1), the organic anion transporting polypeptides OATP-C (SLC21A6), OATP8 (SLC21A8) and OATP-A (SLC21A3), and the multidrug resistance protein MRP3 (ABCC3). Synthesis and transport of Bile Salts are intricately linked processes that undergo extensive feedback and feed-forward regulation by transcriptional and posttranscriptional mechanisms. A key regulator of hepatocellular Bile Salt homeostasis is the Bile acid receptor/farnesoid X receptor FXR, which activates transcription of the BSEP and OATP8 genes and of the small heterodimer partner 1 (SHP). SHP is a transcriptional repressor that mediates Bile acid-induced repression of the Bile Salt uptake systems rat Ntcp and human OATP-C. A nuclear receptor that activates rodent Oatp2 (Slc21a5) and human MRP2 (ABCC2) is the pregnane X receptor/steroid X receptor PXR/SXR. Intracellular trafficking and membrane insertion of Bile Salt transporters is regulated by lipid, protein, and extracellular signal-related kinases in response to physiologic stimuli such as cyclic adenosine monophosphate or taurocholate. Finally, dysfunction of individual Bile Salt transporters such as BSEP, on account of genetic mutations, steric inhibition, suppression of gene expression, or disturbed signaling, is an important cause of cholestatic liver disease.

  • Drug Transporters - Bile Salt Transporters
    Annual review of physiology, 2002
    Co-Authors: Peter J. Meier, Bruno Stieger
    Abstract:

    Bile Salts are the major organic solutes in Bile and undergo extensive enterohepatic circulation. Hepatocellular Bile Salt uptake is mediated predominantly by the Na(+)-taurocholate cotransport proteins Ntcp (rodents) and NTCP (humans) and by the Na(+)-independent organic anion-transporting polypeptides Oatp1, Oatp2, and Oatp4 (rodents) and OATP-C (humans). After diffusion (bound by intracellular Bile Salt-binding proteins) to the canalicular membrane, monoanionic Bile Salts are secreted into Bile canaliculi by the Bile Salt export pump Bsep (rodents) or BSEP (humans). Both belong to the ATP-binding cassette (ABC) transporter superfamily. Dianionic conjugated Bile Salts are secreted into Bile by the multidrug-resistance-associated proteins Mrp2/MRP2. In Bile ductules, a minor portion of protonated Bile acids and monomeric Bile Salts are reabsorbed by non-ionic diffusion and the apical sodium-dependent Bile Salt transporter Asbt/ASBT, transported back into the periductular capillary plexus by Mrp3/MRP3 [and/or a truncated form of Asbt (tAsbt)], and subjected to cholehepatic shunting. The major portion of biliary Bile Salts is aggregated into mixed micelles and transported into the intestine, where they are reabsorbed by apical Oatp3, the apical sodium-dependent Bile Salt transporter (ASBT), cytosolic intestinal Bile acid-binding protein (IBABP), and basolateral Mrp3/MRP3 and tAsbt. Transcriptional and posttranscriptional regulation of these enterohepatic Bile Salt transporters is closely related to the regulation of lipid and cholesterol homeostasis. Furthermore, defective expression and function of Bile Salt transporters have been recognized as important causes for various cholestatic liver diseases.

  • Effects of Bile Salt flux variations on the expression of hepatic Bile Salt transporters in vivo in mice
    Journal of hepatology, 2002
    Co-Authors: Henk Wolters, Bruno Stieger, Baukje M. Elzinga, Julius F. W. Baller, Renze Boverhof, Margrit Schwarz, Henkjan J. Verkade, Folkert Kuipers
    Abstract:

    Abstract Background/Aims : Expression of hepatic Bile Salt transporters is partly regulated by Bile Salts via activation of nuclear farnesoid X-activated receptor (Fxr). We investigated the physiological relevance of this regulation by evaluating transporter expression in mice experiencing different transhepatic Bile Salt fluxes. Methods : Bile Salt flux was manipulated by dietary supplementation with taurocholate (0.5% w/w) or cholestyramine (2% w/w) or by disruption of the cholesterol 7α-hydroxylase-gene ( Cyp7A −/− mice) leading to reduced Bile Salt pool size. Expression of hepatic transporters was assessed (polymerase chain reaction (PCR), immunoblotting, and immunohistochemistry). Results : Biliary Bile Salt secretion was increased (+350%) or decreased (−50%) after taurocholate or cholestyramine feeding, respectively, but plasma Bile Salt concentrations and hepatic Fxr expression were not affected. The Bile Salt uptake system Na + -taurocholate co-transporting polypeptide (Ntcp) and organic anion transporting polypeptide-1 (Oatp1) were down-regulated by taurocholate and not affected by cholestyramine feeding. Cyp7A −/− mice did not show altered Ntcp or Oatp1 expression. Canalicular Bile Salt export pump (Bsep) was up-regulated by 65% in taurocholate-fed mice, and slightly down-regulated in Cyp7A −/− mice. Conclusions : Large variations in hepatic Bile Salt flux have minor effects on expression of murine Ntcp and Bsep in vivo, suggesting that these transporters are abundantly expressed and able to accommodate a wide range of ‘physiological' Bile Salt fluxes.

  • Expression of the Bile Salt export pump is maintained after chronic cholestasis in the rat
    Gastroenterology, 2000
    Co-Authors: John M. Lee, Bruno Stieger, Peter J. Meier, Michael Trauner, Carol J. Soroka, James L. Boyer
    Abstract:

    Abstract Background & Aims: This study assessed the expression of the recently identified adenosine triphosphate–dependent Bile Salt export pump and the functional ability to excrete Bile Salts in cholestatic models in the rat. Methods: The effects of common Bile duct ligation, endotoxin, and ethinylestradiol on Bile Salt export pump messenger RNA levels, protein expression, and tissue localization were determined. Changes in the expression of 3 other hepatocyte membrane transporters (Na + taurocholate cotransporter, multispecific organic anion transporter, and P-glycoprotein) were also determined for comparison. Functional assessment of Bile Salt excretion was determined after Bile duct ligation. Results: Expression of the Bile Salt export pump was diminished but relatively preserved compared with other membrane transporters. Tissue localization of the Bile Salt export pump persisted at the canalicular domain in all 3 models. In contrast, expressions of the Na + taurocholate cotransporter and multispecific organic anion transporter were more profoundly diminished. P-glycoprotein levels increased severalfold with common Bile duct ligation but were unchanged with either endotoxin or ethinylestradiol. The capacity to excrete Bile Salts was relatively maintained 3 and even 14 days after Bile duct ligation. Conclusions: Alterations in expression of the Bile Salt export pump may account for the functional alterations of Bile Salt secretion observed in cholestasis. However, relative preservation of expression is associated with persistent Bile Salt excretion and may lessen the extent of liver injury produced by Bile Salt retention. GASTROENTEROLOGY 2000;118:163-172