NaTC) And Sodium Taurodeoxycholate Research Articles

Morphology of bile salts micelles and mixed micelles with lipolysis products, from scattering techniques and atomistic simulations

HypothesesBile salts (BS) are biosurfactants released into the small intestine, which play key and contrasting roles in lipid digestion: they adsorb at interfaces and promote the adsorption of digestive enzymes onto fat droplets, while they also remove lipolysis products from that interface, solubilising them into mixed micelles. Small architectural variations on their chemical structure, specifically their bile acid moiety, are hypothesised to underlie these conflicting functionalities, which should be reflected in different aggregation and solubilisation behaviour. ExperimentsThe micellisation of two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), which differ by one hydroxyl group on the bile acid moiety, was assessed by pyrene fluorescence spectroscopy, and the morphology of aggregates formed in the absence and presence of fatty acids (FA) and monoacylglycerols (MAG) – typical lipolysis products – was resolved by small-angle X-ray/neutron scattering (SAXS, SANS) and molecular dynamics simulations. The solubilisation by BS of triacylglycerol-incorporating liposomes – mimicking ingested lipids – was studied by neutron reflectometry and SANS. FindingsOur results demonstrate that BS micelles exhibit an ellipsoidal shape. NaTDC displays a lower critical micellar concentration and forms larger and more spherical aggregates than NaTC. Similar observations were made for BS micelles mixed with FA and MAG. Structural studies with liposomes show that the addition of BS induces their solubilisation into mixed micelles, with NaTDC displaying a higher solubilising capacity.

Bulk and interfacial interactions between hydroxypropyl-cellulose and bile salts: Impact on the digestion of emulsified lipids

Hydroxypropyl-cellulose (HPC) is a surface-active, non-digestible polysaccharide, commonly used in food emulsions as thickener and/or emulsifier. Due to these dual characteristics, HPC is a potential ingredient to modulate lipid digestion. Since bile salts (BS) are key players during lipid digestion, the aim of this work was to investigate the impact that interactions of HPC with BS has on the digestion of emulsified lipids. We studied the effect of two BS species differing in bile-acid moiety, sodium-taurocholate (NaTC) and sodium-taurodeoxycholate (NaTDC). A Quartz-Crystal-Microbalance (QCM-D) was used to evaluate HPC-BS interfacial interactions during the sequential and simultaneous adsorption of both components at a hydrophobic surface, while micro-Differential-Scanning-Calorimetry was used to examine bulk interactions. In vitro lipid digestion was studied by using a pH-stat method. Results showed that, under fed-state conditions, NaTDC micelles were more effective at displacing a pre-adsorbed HPC layer from the surface than NaTC monomers. Nevertheless, HPC was resistant to complete displacement by both BS. Additionally, HPC was more susceptible to interact with NaTDC in the bulk, compared to NaTC, which made the adsorption more competitive for NaTDC. The reduced amount of free NaTDC in solution could explain the delayed lipolysis shown by HPC-stabilized emulsions when NaTDC was used to simulate duodenal conditions. These findings show that the delay of lipid digestion by HPC is due to the combined effect of HPC-BS interfacial and bulk interactions, with BS-binding in solution mostly contributing to this effect, and the BS molecular and micellar structure playing essential roles on both situations.

ESR Spectroscopy Insight on the Anticancer Drug Mitoxantrone Location in Membrane Mimetic Systems

The location of mitoxantrone molecule in micelles formed by bile salts (sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC)) and sodium dodecyl sulfate (SDS) have been investigated by electron spin resonance (ESR) spectroscopy, using three doxylstearic acid probes (5-, 12- and 16-doxylstearic acid abbreviated as 5-DSA, 12-DSA and 16-DSA). The analysis of ESR parameters of these spin probes evidenced slower dynamics induced by mitoxantrone that vary in the following order: 12-DSA > 5-DSA > 16-DSA for both bile salts micelles and 5-DSA > 12-DSA > 16-DSA for SDS micelles. The ESR parameters are slightly sensitive to variation of pH. These results indicate that the spin probes target different regions in these aggregates. Keywords: mitoxantrone, bile salts micelles, SDS micelles, ESR spectroscopy

Interactions of bile salts with a dietary fibre, methylcellulose, and impact on lipolysis

Methylcellulose (MC) has a demonstrated capacity to reduce fat absorption, hypothetically through bile salt (BS) activity inhibition. We investigated MC cholesterol-lowering mechanism, and compared the influence of two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), which differ slightly by their architecture and exhibit contrasting functions during lipolysis.BS/MC bulk interactions were investigated by rheology, and BS behaviour at the MC/water interface studied with surface pressure and ellipsometry measurements. In vitro lipolysis studies were performed to evaluate the effect of BS on MC-stabilised emulsion droplets microstructure, with confocal microscopy, and free fatty acids release, with the pH-stat method.Our results demonstrate that BS structure dictates their interactions with MC, which, in turn, impact lipolysis. Compared to NaTC, NaTDC alters MC viscoelasticity more significantly, which may correlate with its weaker ability to promote lipolysis, and desorbs from the interface at lower concentrations, which may explain its higher propensity to destabilise emulsions.

Molecular insights into the behaviour of bile salts at interfaces: a key to their role in lipid digestion

HypothesesUnderstanding the mechanisms underlying lipolysis is crucial to address the ongoing obesity crisis and associated cardiometabolic disorders. Bile salts (BS), biosurfactants present in the small intestine, play key roles in lipid digestion and absorption. It is hypothesised that their contrasting functionalities – adsorption at oil/water interfaces and shuttling of lipolysis products away from these interfaces – are linked to their structural diversity. We investigate the interfacial films formed by two BS, sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), differing by the presence or absence of a hydroxyl group on their steroid skeleton. ExperimentsTheir adsorption behaviour at the air/water interface and interaction with a phospholipid monolayer – used to mimic a fat droplet interface – were assessed by surface pressure measurements and ellipsometry, while interfacial morphologies were characterised in the lateral and perpendicular directions by Brewster angle microscopy, X-ray and neutron reflectometry, and molecular dynamics simulations. FindingsOur results provide a comprehensive molecular-level understanding of the mechanisms governing BS interfacial behaviour. NaTC shows a higher affinity for the air/water and lipid/water interfaces, and may therefore favour enzyme adsorption, whereas NaTDC exhibits a higher propensity for desorption from these interfaces, and may thus more effectively displace hydrolysis products from the interface, through dynamic exchange.

Effect of Different Bile Salts on the Relative Hypoglycemia of Witepsol W35 Suppositories Containing Insulin in Diabetic Beagle Dogs

Insulin suppositories were formulated using Witepsol W35 as a base to investigate the effect of various bile salts/acids on the plasma glucose concentration of diabetic beagle dogs. Comparison of the effect of these formulations was made with that produced by insulin subcutaneous injections. Of the bile salts/acids studied, incorporation of 100 mg of deoxycholic acid (DCA), sodium cholate (NaC), or sodium deoxycholate (NaDC) with insulin (10 U/Kg) showed that suppositories containing NaDC produced the highest area under the curve (AUC) and relative hypoglycemia (RH) of 290 ± 83 mg%h and 28% ± 8.1%, respectively. To study the optimum amount of NaDC in insulin suppositories to produce the highest RH, 50–200 mg/suppository were used, and we found that 150 mg NaDC produced 35% ± 13% RH. We also studied the influence of different doses of insulin (5–20 U/kg) in the presence of NaDC (100 mg). It was found that increase of the insulin dose was accompanied by an increase in AUC and maximum reduction in plasma glucose level Cmax. A combination of NaDC (100 mg) and NaC (50 mg) produced an AUC of 252 ± 13 mg% h and an RH of 49% ± 2.6%, which were higher than produced by either of its individual components (NaC 50 mg or NaDC 100 mg) when used alone or when compared with an equivalent amount of NaDC (150 mg). When the effect of sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC) was studied, it was found that an insulin suppository containing 100 mg of either NaTC or NaTDC produced an RH equivalent to that produced previously with a mixture of NaDC (100 mg) and NaC (50 mg). On the other hand, NaC (50 mg) did not improve the hypoglycemic effect of NaTC any further. In conclusion, a relative hypoglycemia of about 50% can be reached using insulin suppositories containing Witepsol W35 as a base and NaDC plus NaC (100 mg plus 50 mg, respectively), NaTDC (100 mg), or NaTC (100 mg) as rectal absorption enhancers of insulin. A desirable hypoglycemia, expressed as Cmax, and/or AUC can be reached by adjusting the insulin dose in the formulation according to the degree of hyperglycemia.

Mixed Adsorbed Film and Micelles of Sodium Taurocholate and Sodium Taurodeoxycholate

Abstract The surface tension of an aqueous mixture of sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC) in the presence of 0.1 mol kg−1 sodium chloride was measured as a function of the total concentration and composition of the bile salts at 25°C. The result, processed by a thermodynamic treatment based on excess thermodynamic quantities, showed that NaTC and NaTDC are freely miscible in an adsorbed film, while mixing in a limited composition region of the micelle.