SolubilityofCholesterolinQuaternaryMixturesofBileSalt,Lecithin,InorganicSalt,andWaterat310.2KJieLu,*,†DanhuiWu,†LianweiChen,†LijuanZhang,‡andShiminMao§†SchoolofChemical&MaterialEngineering,JiangnanUniversity,Wuxi214122,People’sRepublicofChina‡SchoolofChemistry&ChemicalEngineering,ShanghaiUniversityofEngineeringScience,Shanghai201620,People’sRepublicofChina§DepartmentofChemicalEngineering&AppliedChemistry,UniversityofToronto,Toronto,OntarioM5S3E5,CanadaABSTRACT:Thesolubilityofcholesterol(Ch)inquaternarymixturesofbilesalt(BS),lecithin(L),inorganicsalt(Ca2+),andwater,whichcanbeusedasmodelbileswasmeasuredat310.2Kinthiswork.Theaccurateconcentrationsofbilesalt,lecithin,andcholesterolweredeterminedbyhighperformanceliquidchromatography(HPLC).Theeffectofbilesalt/lecithinmolarratio,bilesaltconcentration,totallipidconcentration,andCa2+concentrationonthesolubilityofcholesterolwereinvestigatedindetail.Theresultsshowthatthecholesterolsolubilitymonotonicallyincreaseswiththeincreaseoftheconcentrationofbilesaltortotallipid.Thecholesterolsolubilityfirstincreaseswiththebilesalt/lecithinmolarratiowhenthebilesalt/lecithinmolarratioislowerthan1andthendecreaseswhenthebilesalt/lecithinmolarratiofurtherincreases.Inaddition,theexistenceofCa2+inthemodelbileswillsignificantlydecreasethesolubilityofcholesterol.■INTRODUCTIONInrecentyears,cholesterolcholelithiasishasbeenemergingasoneofthemostcommondigestivediseases,ofwhichtheprevalenceratehasconsiderablyincreaseduptoabout10%asaresultofincreasedprevalenceofoverweightandahigherproportionoftheelderlyinthepopulation.1,2Gallstonesgenerallycanbecategorizedintothreemajortypes,3cholesterolstones(inwhichthecontentofcholesterolismorethan70%byweight),mixedstones(inwhichtheresimultaneouslyexistawidevarietyofcholesterolandbilirubinates),andpigmentstones(inwhichthemaincomponentsarevariousbilirubinatesandthecontentofcholesterolislessthan10%byweight).4−8SethiandJohnson9havesummarizedthepathogenesisofgallstonesasfollows:whencholesterolexceedstheamountthatcanbesolubilizedbythemicellesandvesiclesinbile,theformationofcholesterolstonesmaytakeplace;whenthereisanexcessofpigmentsandothercomponentsinbileduetobacterialinfectionorotherfactors,theyshallprecipitateandformpigmentstones;whenfinecrystalsofcholesterolorotherdebrisappearinbile,bacteriamaysettledownandreproduceontheirsurfacewhichshallresultinmixedgallstones.10Inaddition,someproteinssuchasα1-acidglycoprotein,11α1-antichymotrypsin,12haptoglobin,13apoprotein14inbilehavebeenfoundtoactaspromotersorinhibitorsofgallstoneformation.Bilecanberegardedasakindofcomplexbiofluidmainlycomposedofwater(about80to96%inmass);however,cholesterolisgenerallyinsolubleinaqueousmedia.Intheirstudiesonthephysicalchemistryofcholesterolsolubilityinbile,CareyandSmall15havefirstputforwardatriangularcoordinatesysteminwhichthreeverticesindicatepurecholesterol,lecithin,andbilesalt,respectively.Withthechangeoftheirconcentrations,thebilewillfinallyequilibrateintoonephase(micelles),twophases(micellesandvesicles,micellesandcrystals),orthreephases(micelles,vesicles,andcrystals),andcholesterolispackedinthemicellesandvesicles.Supersaturationandevencrystallizationofcholesterolshalltakeplacewhentheamountofcholesterolsecretedintobileishigherthanwhichmicellesandvesiclescancompletelysolubilize.16,17Todetermineinvitrothesolubilityofcholesterolinbile,pr...
