Effects of bile salt and phospholipid hydrophobicity on lithogenicity of human gallbladder bile

Abstract

Abstract. Increased biliary bile salt and phospholipid hydrophobicity may promote nucleation of cholesterol crystals and gallstone formation. We therefore compared bile salt composition (determined by gasliquid chromatography) in patients with cholesterol (n = 35) and pigment (n = 16) gallstones (group A). Bile salt composition and cumulative bile salt hydrophobicity index were not different between both stone types. Hydrophobicity index or YO of individual bile salts did not correlate with cholesterol saturation index or nucleation time. In an additional 21 cholesterol stone patients (group B) biliary bile salt and phospholipid hydrophobicity as determined by highpressure liquid chromatography did not correlate with cholesterol saturation index or nucleation time. In both group A and group B, cholesterol stone patients with cholesterol crystals in their fresh biles had a higher % deoxycholic acid, a lower YO cholic acid and a higher bile salt hydrophobicity index than crystal-negative patients. This study indicates the need for further research on the role of bile salt hydrophobicity in the pathogenesis of gallstones.

Effects of bile salt hydrophobicity on crystallization of cholesterol in model bile

“…2 g dL ÿ 1 ) with a very unphysiological composition (97 . Third, two recent studies found a positive correlation of percentage of deoxycholate with cholesterol saturation index as well as with nucleation time in bile [22,24] (a third study from our group, however, did not find such a correlation [17]). The relevance for human gallstone formation therefore was uncertain.…”

“…These forms (filaments, tubules, spirals) might be metastable intermediates of-probably anhydrous-cholesterol in the process of formation of the classical triclinic cholesterol monohydrate crystals [3]. Moreover, our group [17] and Angelico et al [18] found that molecular composition and cumulative hydrophobicity of the phospholipid mixture in human bile are regulated within a very narrow range and do not correlate with nucleation time of cholesterol crystals. Although it was previously suggested that phospholipid molecular composition might be important in this respect, this was based on experiments in very dilute model biles (TLCo 1 .…”

“…The relevance for human gallstone formation therefore was uncertain. Moreover, our group [17] and Angelico et al [18] found that molecular composition and cumulative hydrophobicity of the phospholipid mixture in human bile are regulated within a very narrow range and do not correlate with nucleation time of cholesterol crystals. Although there is more variation in biliary bile salt composition, its role in cholesterol gallstone formation is controversial.…”

Phosphatidylcholine-enriched diet prevents gallstone formation in mice susceptible to cholelithiasis

“…Research interest during the last two decades has been focused on the metabolism of biliary lipids and its relationship to gallstone formation (3,4). It has become evident that a disturbed metabolism of cholesterol and/or bile salt constitutes a major factor in gallstone formation (5,6). In bile, bile salts, phospholipids (PLs), and cholesterol are the major lipid components (7) and, depending on their relative concentrations, they interact to form several different biliary lipid micelles (8).…”

Targets for Current Pharmacologic Therapy in Cholesterol Gallstone Disease

“…Increasing biliary UDCA, in turn, results in a decreased hepatic secretion of biliary cholesterol and the formation of unsaturated gallbladder bile (i.e. containing less cholesterol in solution) with a cholesterol saturation index of less than 1 (81-83) (Figure 2). This step represents a key factor in initiating the process of dissolution of cholesterol crystals and gallstones.…”