Interactions between organic anions, micelles and vesicles in model bile systems

Abstract

Biliary lipid secretion probably involves both 'micellization' and 'vesiculization' of bile-canalicular membrane lipids. Several hydrophilic organic anions inhibit the secretion of lipids into the bile without altering bile salt secretion [Verkade, Vonk and Kuipers (1995) Hepatology 21, 1174-1189]. Hydrophobic organic anions do not interfere with biliary lipid secretion. We investigated whether the organic-anion-induced inhibition of biliary lipid secretion in vivo could be attributed to inhibition of micellization, by the application of in vitro models of micellization. Carboxyfluorescein was entrapped in a self-quenching concentration in small unilamellar vesicles (SUV) composed of cholesterol/egg phosphatidylcholine (molar ratios 0, 0.2 and 0.5). Certain organic anions clearly affected the bile-salt-induced release of fluorescence from these SUV, reflecting interference with micellization. However, the effects of hydrophilic and hydrophobic organic anions did not correspond with their effects on biliary lipid secretion in vivo, irrespective of the bile salt species used (taurocholate, taurodeoxycholate or tauroursodeoxycholate) and of the lipid composition of the SUV. Ultracentrifugation and dynamic light-scattering studies indicated that organic anions do interact with bile salt/ phosphatidylcholine/cholesterol mixed micelles, but that they do not inhibit micellization, for example by competing with phosphatidylcholine and/or cholesterol for incorporation into mixed micelles. In conclusion, the present in vitro data indicate that the in vivo mechanism of organic-anion-induced inhibition of biliary lipid secretion is not mediated by inhibition of micellization.

Interactions of Indocyanine Green and Lipid in Enhancing Near-Infrared Fluorescence Properties: The Basis for Near-Infrared Imaging in Vivo

“…It is possible that ICG with its high LogP value (6.05 at pH 7.4; low water solubility) may bind to lipid and cause the liposome membrane to become sticky, thus forming liposome aggregations, detected by 90° light scattering and photon correlation spectroscopy as ICG induced an increase in the light scattering and apparent diameter (Figure ). Others have mixed ICG with preformed liposomes composed of various lipids and observed aggregation or fluorescence enhancement. , However, these studies did not probe concentration-dependent effects. In our studies, we evaluated and found nonlinear concentration effects and used the information for ICG–liposome admixtures related to ICG–lipid binding and fluorescence enhancement to fine-tune an optimal composition to construct ICG incorporated completely into liposome membranes.…”

“…It is possible that ICG with its high LogP value (6.05 at pH 7.4; low water solubility) 18 may bind to lipid and cause the liposome membrane to become sticky, thus forming liposome aggregations, detected by 90° light scattering and photon correlation spectroscopy as ICG induced an increase in the light scattering and apparent diameter (Figure 1 ). Others have mixed ICG with preformed liposomes composed of various lipids and observed aggregation 19 or fluorescence enhancement. 14 , 20 However, these studies did not probe concentration-dependent effects.…”

New insights into the mechanism of bile acid—induced biliary lipid secretion

“…221 This conclusion has been supported by a number of in uitro studies, which have indicated the relative efficacy of micellar bile acids to extract lipids from isolated liver plasma, erythrocyte, or model membranes. 106,190,[222][223][224][225] Recent work by Cohen et alZ2' showed that bile acids showed selectivity toward the cesses. 173,174,181 years .…”

Bilirubin and beyond: A review of lipid status in Gilbert’s syndrome and its relevance to cardiovascular disease protection

“…Bile and duodenal cannulas were joined to maintain the enterohepatic circulation of biliary components.When BDT was subsequently infused in both animals, its excretion was strongly and negatively correlated to the lipid:bile acid ratio of bile (r=-0.97), supporting a dose dependent effect of canalicular BDT in uncoupling lipid excretion. Upon gel filtration chromatogragphy of bile, bilirubin co-eluted with bile salts and not with biliary phospholipids or cholesterol, implicating an intracanalicular association between hydrophilic anions and bile salts mediating the uncoupling effect[110].To assess whether organic anions, including BDT, exerted their uncoupling effects by interfering with biliary micellisation, Verkade et al[112] studied their effects in model bile systems. In a system comprising of taurocholate, phospholipid and cholesterol the addition of BDT (5mM) did not affect mean vesicle particle size, in contrast to that of other organic anions, Rose Bengal (hydrophobic) and sulphated taurolithocholate (hydrophilic).…”