Az epekőbetegségek kialakulásában számos gén működését teszik felelőssé, melyek kapcsolatba hozhatók elsődlegesen a máj betegségeivel, az epeelfolyási és -képződési rendellenességekkel, a lipidmetabolizmus módosulásával, diabetes mellitussal, obesitassal, glutensensitiv enteropathiával, Crohn-betegséggel, Down-szindrómával, Gaucher-kórral, cysticus fibrosissal, valamint haematológiai kórképekkel és ileumresectiot követő állapottal. Kialakulásában szerepet játszanak gyógyszermellékhatások, bakteriális fertőzések, gyulladások, fémionterhelés és szabadgyökös reakciók. A zsírmájból az epébe telítetlen zsírsavak, lipidoxidok, diénkonjugátumok, és egyéb lipidperoxidációs termékek kerülnek, melyek az epevezetékben és a hólyagban primer és szekunder szabadgyökös folyamatokat indítanak el. Az epehólyagfalban lejátszódó gyulladásos folyamatok szabadgyöktermeléssel járnak. Az epe szabad bilirubin-tartalma koncentrációfüggően pro-, illetve antioxidánsként viselkedik. Az ambivalens tulajdonságú szabad bilirubin, amely a mikroszómák szivárgása révén, illetve a bél felől a baktériumok deglükorinidáló hatása következtében kimutatható mennyiségben van jelen az epehólyagban, a szabadgyökös reakciókat felerősíti. A szabad bilirubin kőalkotó reakciója az epében jelen lévő fémionokkal, elsődlegesen a Ca ++ -ionokal kalcium-(hidrogén)-bilirubinátot eredményez. A Ca ++ a zsírsavakkal is reakcióba lép, és ezzel megváltoztatja az epe viszkozitását. A lipidek, a szabad bilirubin és a fémionok együttesen kőalkotó komponensek. Az antioxidánsok, illetve azok derivátumai vagy hatásukban antioxidáns tulajdonságot fokozó vegyületek, készítmények több szinten is kedvezően befolyásolhatják az epe összetételét, illetve az epekőképződés gátlását.
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