Katabolická dráha hemu v patogenezi jaterních onemocnění.
Heme catabolic pathway in pathogenesis of liver diseases
dissertation thesis (DEFENDED)
- Kvalifikační práce 
Faculty / Institute
First Faculty of Medicine
Institute of Medical Biochemistry and Laboratory Medicine First Faculty of Medicine
Date of defense
16. 6. 2015
PublisherUniverzita Karlova, 1. lékařská fakulta
KeywordsKeywords not found
This thesis focuses on the role of heme catabolic pathway in the pathogenesis of selected liver diseases. The aim was to clarify if the modulation of heme oxygenase (Hmox) and its catabolic products - especially carbon monoxide (CO) and bilirubin - affected the development and progression of liver diseases, focusing on inflammatory and cholestatic pathways. Firstly, we discovered that the induction of hmox1 prevented hepatocellular damage in endotoxin-induced inflammation. Furthermore, administration of CO in vivo in early-phase of endotoxin-induced cholestasis decreased the inflammatory cytokine production in the liver and simultaneously prevented downregulatory effect of cytokines on hepatocyte transporters resulting in hepatoprotection. For the first time, we characterized in vivo tissue distribution and elimination of inhaled CO in rats. In vitro experiments and the model of extrahepatic cholestasis revealed the significant role of intracellular bilirubin in hepatocellular protection against oxidative damage which accompanies cholestatic disorders. Last but not least, hmox1 induction by heme increased hepatocyte transporters expression and subsequently stimulated bile flow participating in conferring protection against estrogen-induced cholestasis. Presented results demonstrate that the heme...