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Alteration of transport proteins expression during intrahepatic cholestasis in rats
Kolouch, Jan ; Doleželová, Eva (advisor) ; Cermanová, Jolana (referee)
Jan Kolouch Alteration of transport proteins expression during intrahepatic cholestasis in rats Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Pharmacy Background: The aim of the diploma thesis was the verification of cholestatic liver injury by biochemical analysis of plasma and analysis of the main efflux and uptake hepatic transporters (Ntcp, Oatp1a4, Bsep, Mrp2, Mrp3, Mrp4) at the mRNA level. Methods: Wistar rats (n = 6, in each group; 280 - 320 g) were divided into two groups: Control group (LPS-K) and LPS group (lipopolysaccharide was administred at once i.p., 4mg/kg). Blood and liver samples were collected 12 hours after LPS administration. Biochemical analysis of plasma was performed by Cobas Integra ® 800 and GC/MS. Changes of mRNA expression of the transporters were evaluated by qRT-PCR. Results: In comparison to control group, LPS group showed significantly elevated plasmatic levels of the bile acids and also elevated activity of ALP and GMT. Plasmatic levels of bile acids were elevated to 818%, activity of ALP was elevated to 311% and activity of GMT to 2167%. Intrahepatic cholestasis led to the significant decrease of mRNA levels - Ntcp to 4.6%, Oatp1a4 to 2.2%, Mrp2 to 1.7% and Bsep to 25%. Conclusion: According to the results of this study, it is...
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Influence of resveratrol on bile flow.
Paclíková, Kristýna ; Doleželová, Eva (advisor) ; Cermanová, Jolana (referee)
Kristýna Paclíková Influence of resveratrol on bile flow Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Pharmacy Background: Protective effect of resveratrol is shown in many experimental models of cholestasis, but its effect on bile production in healthy individuals has not been studied yet. As the use of resveratrol is frequent in population, the aim of this thesis was to investigate the effect of resveratrol on the bile flow in healthy animals and the clarification of the mechanism of this effect. Methods: Wistar rats (n = 6, in each group, weighing 280 to 320 g) were divided into two groups: control group (Control) and the group of rats administered with resveratrol (10mg/kg/day, p.o.) for 28 days (RES). In vivo clearance study was performed to analyze bile production. Analysis of mRNA and protein expression of the transport proteins was performed by qRT-PCR and Western blot. Results: Resveratrol led to a significant increase in the cumulative bile flow. Analysis of mRNA and protein expression of the transport proteins revealed that bile flow is changed due to posttranscriptional induction of canalicular transporters Bsep and Mrp2. Simultaneously, resveratrol led to induction of Mrp4 efflux protein, expressed at the basolateral membrane of hepatocytes....
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Alteration of transport proteins expression during intrahepatic cholestasis in rats
Kolouch, Jan ; Doleželová, Eva (advisor) ; Cermanová, Jolana (referee)
Jan Kolouch Alteration of transport proteins expression during intrahepatic cholestasis in rats Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Pharmacy Background: The aim of the diploma thesis was the verification of cholestatic liver injury by biochemical analysis of plasma and analysis of the main efflux and uptake hepatic transporters (Ntcp, Oatp1a4, Bsep, Mrp2, Mrp3, Mrp4) at the mRNA level. Methods: Wistar rats (n = 6, in each group; 280 - 320 g) were divided into two groups: Control group (LPS-K) and LPS group (lipopolysaccharide was administred at once i.p., 4mg/kg). Blood and liver samples were collected 12 hours after LPS administration. Biochemical analysis of plasma was performed by Cobas Integra ® 800 and GC/MS. Changes of mRNA expression of the transporters were evaluated by qRT-PCR. Results: In comparison to control group, LPS group showed significantly elevated plasmatic levels of the bile acids and also elevated activity of ALP and GMT. Plasmatic levels of bile acids were elevated to 818%, activity of ALP was elevated to 311% and activity of GMT to 2167%. Intrahepatic cholestasis led to the significant decrease of mRNA levels - Ntcp to 4.6%, Oatp1a4 to 2.2%, Mrp2 to 1.7% and Bsep to 25%. Conclusion: According to the results of this study, it is...
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