1 Abstract In this thesis I have focused on the role of lipids in the pathogenesis of liver diseases, specifically on cholestasis and non-alcoholic fatty liver disease (NAFLD). The first major aim was to clarify the changes in liver ganglioside metabolism in various types of cholestasis and to elucidate the role of heme oxygenase-1 (HMOX1) and associated oxidative stress. The second objective was to determine the effects of n-3 polyunsaturated fatty acids (n-3 PUFA) administration on NAFLD development in a rodent dietary model of NAFLD and in patients with metabolic syndrome and NAFLD. Our results suggest that increased ganglioside biosynthesis and their re-distribution might represent a general protective mechanism of hepatocytes under cholestatic conditions (both estrogen-induced and obstructive aetiology). These changes are closely related to oxidative stress and might protect hepatocytes against deleterious effect of accumulated bile acids. The lack of HMOX1 activity and subsequent oxidative stress potentiate pathological changes in the liver and resulted in tissue-specific modulation of synthesis and re-distribution of gangliosides (in vivo and in vitro). Contrary to it, HMOX1 activation has an opposite effect and may represent a general hepatoprotective mechanism. We have proven that observed changes...
| Identifer | oai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:397736 |
| Date | January 2019 |
| Creators | Šmíd, Václav |
| Contributors | Muchová, Lucie, Rumlová, Michaela, Mičuda, Stanislav |
| Source Sets | Czech ETDs |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis |
| Rights | info:eu-repo/semantics/restrictedAccess |
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