In Vitro Cytotoxicity of the Bile Acids and Bile Acid Derivatives

2013 ◽  
pp. 1531-1540
Author(s):  
Xiangzheng Hu ◽  
Hongjian Zhou ◽  
Guangzhen Song ◽  
Anjun Liu ◽  
Lixia Wang
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
In Vitro Cytotoxicity ◽  
Bile Acid Derivatives

scholarly journals Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Stef De Lombaerde ◽  
Ken Kersemans ◽  
Sara Neyt ◽  
Jeroen Verhoeven ◽  
Christian Vanhove ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Membrane Vesicles ◽  
Hepatic Uptake ◽  
Hepatobiliary Transport ◽  
Bile Acid Transporters ◽  
Significant Difference ◽  
The Impact

Introduction. An in vivo determination of bile acid hepatobiliary transport efficiency can be of use in liver disease and preclinical drug development. Given the increased interest in bile acid Positron Emission Tomography- (PET-) imaging, a further understanding of the impact of 18-fluorine substitution on bile acid handling in vitro and in vivo can be of significance. Methods. A number of bile acid analogues were conceived for nucleophilic substitution with [18F]fluoride: cholic acid analogues of which the 3-, 7-, or 12-OH function is substituted with a fluorine atom (3α-[18F]FCA; 7β-[18F]FCA; 12β-[18F]FCA); a glycocholic and chenodeoxycholic acid analogue, substituted on the 3-position (3β-[18F]FGCA and 3β-[18F]FCDCA, resp.). Uptake by the bile acid transporters NTCP and OATP1B1 was evaluated with competition assays in transfected CHO and HEK cell lines and efflux by BSEP in membrane vesicles. PET-scans with the tracers were performed in wild-type mice (n=3 per group): hepatobiliary transport was monitored and compared to a reference tracer, namely, 3β-[18F]FCA. Results. Compounds 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA were synthesized in moderate radiochemical yields (4–10% n.d.c.) and high radiochemical purity (>99%); 7β-[18F]FCA and 12β-[18F]FCA could not be synthesized and included further in this study. In vitro evaluation showed that 3α-FCA, 3β-FGCA, and 3β-FCDCA all had a low micromolar Ki-value for NTCP, OATP1B1, and BSEP. In vivo, 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA displayed hepatobiliary transport with varying efficiency. A slight yet significant difference in uptake and efflux rate was noticed between the 3α-[18F]FCA and 3β-[18F]FCA epimers. Conjugation of 3β-[18F]FCA with glycine had no significant effect in vivo. Compound 3β-[18F]FCDCA showed a significantly slower hepatic uptake and efflux towards gallbladder and intestines. Conclusion. A set of 18F labeled bile acids was synthesized that are substrates of the bile acid transporters in vitro and in vivo and can serve as PET-biomarkers for hepatobiliary transport of bile acids.

scholarly journals Downregulation of CTRP-3 by Weight Loss In Vivo and by Bile Acids and Incretins in Adipocytes In Vitro

2020 ◽  
Vol 21 (21) ◽  
pp. 8168
Author(s):  
Andreas Schmid ◽  
Jonas Gehl ◽  
Miriam Thomalla ◽  
Alexandra Hochberg ◽  
Anja Kreiß ◽  
...  
Keyword(s):  
Weight Loss ◽  
Bile Acid ◽  
Bile Acids ◽  
Serum Levels ◽  
Receptor Expression ◽  
Low Calorie Diet ◽  
Calorie Diet ◽  
Bile Acid Receptor

The adipokine CTRP-3 (C1q/TNF-related protein-3) exerts anti-inflammatory and anti-diabetic effects. Its regulation in obesity and during weight loss is unknown. Serum and adipose tissue (AT) samples were obtained from patients (n = 179) undergoing bariatric surgery (BS). Moreover, patients (n = 131) participating in a low-calorie diet (LCD) program were studied. CTRP 3 levels were quantified by ELISA and mRNA expression was analyzed in AT and in 3T3-L1 adipocytes treated with bile acids and incretins. There was a persistent downregulation of CTRP-3 serum levels during weight loss. CTRP-3 expression was higher in subcutaneous than in visceral AT and serum levels of CTRP-3 were positively related to AT expression levels. A rapid decrease of circulating CTRP-3 was observed immediately upon BS, suggesting weight loss-independent regulatory mechanisms. Adipocytes CTRP-3 expression was inhibited by primary bile acid species and GLP 1. Adipocyte-specific CTRP-3 deficiency increased bile acid receptor expression. Circulating CTRP-3 levels are downregulated during weight loss, with a considerable decline occurring immediately upon BS. Mechanisms dependent and independent of weight loss cause the post-surgical decline of CTRP-3. The data strongly argue for regulatory interrelations of CTRP-3 with bile acids and incretin system.

scholarly journals Microwave-assisted green synthesis of bile acid derivatives and evaluation of glucocorticoid receptor binding

2020 ◽  
Author(s):  
Bojana R. Vasiljević ◽  
Edward T. Petri ◽  
Sofija S. Bekić ◽  
Andjelka S. Ćelić ◽  
Ljubica M. Grbović ◽  
...  
Keyword(s):  
Bile Acid ◽  
Microwave Irradiation ◽  
Glucocorticoid Receptor ◽  
Ligand Binding ◽  
Green Synthesis ◽  
Bile Acids ◽  
Receptor Binding ◽  
Microwave Assisted ◽  
Bile Acid Derivatives ◽  
Cholanic Acid

Green synthesis of bile acids derivatives and 5β-cholanic acid was achieved under microwave irradiation, and the binding affinity for the ligand binding domain of the glucocorticoid receptor was measured.

Interaction between bile acids and staphylococcal polysaccharide: inhibition of capsule formation in encapsulated mutant strains (taurine+, taurine−) of Staphylococcus aureus

1983 ◽  
Vol 29 (12) ◽  
pp. 1653-1660 ◽  
Author(s):  
Toshichika Ohtomo
Keyword(s):  
Staphylococcus Aureus ◽  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Taurocholic Acid ◽  
Polysaccharide Antigen ◽  
Capsule Formation ◽  
Mutant Strains ◽  
Bile Acid Derivatives ◽  
Capsular Material

In a previous paper, we showed that bile acid derivatives inhibit capsule formation as well as taurine biosynthesis in a taurine+ (Tau+) encapsulated strain of Staphylococcus aureus. In the present study, binding of [14C]cholic acid ([14C]CA) and [14C]taurocholic acid ([14C]TA) to the staphylococcal polysaccharide antigen (SPA) of the capsular fraction was examined. The bile acids were found to bind with SPA via taurine of the Tau+ cells. [14C]CA bound with the SPA fraction of the Tau+ strain within 10–30 min, whereas 60–120 min was required in the binding of [14C]TA. Various bile acids competed with cholic acid binding to Tau+ cells which was shown by the inhibition of binding with cholic acid or taurocholic acid but not with glycholic acid. Binding of bile acid derivatives to a Tau− encapsulated mutant or to capsular material from this mutant was not observed.

In vitro inhibition of OATP-mediated uptake of phalloidin using bile acid derivatives

2009 ◽  
Vol 239 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Elisa Herraez ◽  
Rocio I.R. Macias ◽  
Jose Vazquez-Tato ◽  
Marta Vicens ◽  
Maria J. Monte ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acid Derivatives ◽  
In Vitro Inhibition

Synthesis and in vitro cytotoxicity of deoxyadenosine–bile acid conjugates linked with 1,2,3-triazole

2013 ◽  
Vol 37 (11) ◽  
pp. 3559 ◽  
Author(s):  
Daniela Perrone ◽  
Olga Bortolini ◽  
Marco Fogagnolo ◽  
Elena Marchesi ◽  
Lara Mari ◽  
...  
Keyword(s):  
Bile Acid ◽  
In Vitro Cytotoxicity

scholarly journals Bile acid metabolism is altered in multiple sclerosis and supplementation ameliorates neuroinflammation

2019 ◽  
Author(s):  
Pavan Bhargava ◽  
Leah Mische ◽  
Matthew D. Smith ◽  
Emily Harrington ◽  
Kathryn C Fitzgerald ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
White Matter Lesions ◽  
The Body ◽  
Bile Acid Metabolism ◽  
Dependent Manner ◽  
Microglial Polarization

AbstractMultiple sclerosis (MS) is an inflammatory demyelinating disorder of the CNS. Bile acids are cholesterol metabolites that can signal through receptors on cells throughout the body, including the CNS and immune system. Whether bile acid metabolism is abnormal in MS is unknown. Using global and targeted metabolomic profiling, we identified lower levels of circulating bile acid metabolites in multiple cohorts of adult and pediatric MS patients compared to controls. In white matter lesions from MS brain tissue, we noted the presence of bile acid receptors on immune and glial cells. To mechanistically examine the implications of lower levels of bile acids in MS, we studied the in vitro effects of an endogenous bile acid – tauroursodeoxycholic acid (TUDCA) on astrocyte and microglial polarization. TUDCA prevented neurotoxic (A1) polarization of astrocytes and pro-inflammatory polarization of microglia in a dose-dependent manner. TUDCA supplementation in experimental autoimmune encephalomyelitis reduced severity of disease, based on behavioral and pathological measures. We demonstrate that bile acid metabolism is altered in MS; bile acid supplementation prevents polarization of astrocytes and microglia to neurotoxic phenotypes and ameliorates neuropathology in an animal model of MS. These findings identify dysregulated bile acid metabolism as a potential therapeutic target in MS.

scholarly journals Retention of Primary Bile Acids by Lupin Cell Wall Polysaccharides Under In Vitro Digestion Conditions

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2117 ◽  
Author(s):  
Naumann ◽  
Schweiggert-Weisz ◽  
Haller ◽  
Eisner
Keyword(s):  
Cell Wall ◽  
Bile Acid ◽  
Bile Acids ◽  
Molecular Interactions ◽  
Enterohepatic Circulation ◽  
In Vitro Digestion ◽  
Adsorptive Capacity ◽  
Cell Wall Polysaccharides ◽  
Dietary Fibres

Interference of dietary fibres with the enterohepatic circulation of bile acids is proposed as a mechanism for lowering cholesterol. We investigated how lupin hull and cotyledon dietary fibres interact with primary bile acids using an in vitro model under simulated upper gastrointestinal conditions. Cell wall polysaccharides were isolated and extracted to separate pectin-like, hemicellulosic, and lignocellulosic structures. Lupin hull consisted mainly of structural components rich in cellulose. The viscosity of the in vitro digesta of lupin hull was low, showing predominantly liquid-like viscoelastic properties. On the other hand, lupin cotyledon fibre retarded bile acid release due to increased viscosity of the in vitro digesta, which was linked with high contents of pectic polymers forming an entangled network. Molecular interactions with bile acids were not measured for the hull but for the cotyledon, as follows: A total of 1.29 µmol/100 mg DM of chenodesoxycholic acids were adsorbed. Molecular interactions of cholic and chenodesoxycholic acids were evident for lignin reference material but did not account for the adsorption of the lupin cotyledon. Furthermore, none of the isolated and fractionated cell wall materials showed a significant adsorptive capacity, thus disproving a major role of lupin cell wall polysaccharides in bile acid adsorption.

scholarly journals In Vitro Interactions of Dietary Fibre Enriched Food Ingredients with Primary and Secondary Bile Acids

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1424 ◽  
Author(s):  
Susanne Naumann ◽  
Ute Schweiggert-Weisz ◽  
Julia Eglmeier ◽  
Dirk Haller ◽  
Peter Eisner
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Dietary Fibre ◽  
In Vitro Digestion ◽  
Food Ingredients ◽  
Bile Acid Pool Size ◽  
As Adsorption ◽  
Secondary Bile Acids ◽  
In Vitro Interactions

Dietary fibres are reported to interact with bile acids, preventing their reabsorption and promoting their excretion into the colon. We used a method based on in vitro digestion, dialysis, and kinetic analysis to investigate how dietary fibre enriched food ingredients affect the release of primary and secondary bile acids as related to viscosity and adsorption. As the main bile acids abundant in humans interactions with glyco- and tauroconjugated cholic acid, chenodesoxycholic acid and desoxycholic acid were analysed. Viscous interactions were detected for apple, barley, citrus, lupin, pea, and potato derived ingredients, which slowed the bile acid release rate by up to 80%. Adsorptive interactions of up to 4.7 μmol/100 mg DM were significant in barley, oat, lupin, and maize preparations. As adsorption directly correlated to the hydrophobicity of the bile acids the hypothesis of a hydrophobic linkage between bile acids and dietary fibre is supported. Delayed diffusion in viscous fibre matrices was further associated with the micellar properties of the bile acids. As our results indicate changes in the bile acid pool size and composition due to interactions with dietary fibre rich ingredients, the presented method and results could add to recent fields of bile acid research.

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