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Dynamics of Changes in Bile Acid Metabolomics in Estrogen-Induced Cholestasis
 Alaei Faradonbeh, Fatemeh ; Mičuda, Stanislav (advisor) ; Večeřa, Rostislav (referee) ; Muchová, Lucie (referee)
Dynamics of changes in bile acid metabolomics in estrogen-induced cholestasis Bile acids are essential endobiotics with numerous exocrine and endocrine functions. In this dissertation, we evaluate three factors that were suspected of modifying bile acid metabolomics: i) the effect of metformin in estrogen-induced cholestasis, ii) the role of MRP2 (multidrug resistance-associated protein 2) protein in the described risk of more frequent intrahepatic cholestasis in pregnancy, and iii) the excessive iron accumulation in the liver. Metformin has been tested for its potential use in women with gestational diabetes mellitus (GDM) who have a higher incidence of intrahepatic cholestasis (ICP). As an ICP model, we used experimental cholestasis induced in mice by administration of ethinylestradiol. Administration of metformin in this situation significantly increased bile acid concentrations in the systemic circulation, which reached values considered significantly toxic in pregnant women. These data suggest that the possibility of developing ICP is accentuated when metformin is used in pregnant women. In another study, we demonstrated that the MRP2 transporter plays a significant role in biliary bile acid elimination and that the genetic defect itself caused an increase in the plasma concentrations in rats....
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