- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Epigallocatechin gallate (EGCG) has been shown to be protective in various experimental models of liver injury, although opposite effects have also been reported. Since its effect on biliary physiology has not been thoroughly investigated, the present study evaluated effect of EGCG on bile flow and bile acid homeostasis in rats. Compared to controls, EGCG treatment decreased bile flow by 23%. Hepatic paracellular permeability and biliary bile acid excretion were not altered by EGCG administration, but biliary glutathione excretion was reduced by 70%. Accordingly, the main glutathione transporter on the hepatocyte canalicular membrane, multidrug resistance-associated protein 2 (Mrp2), was significantly decreased at the protein level. EGCG administration also doubled plasma bile acid levels compared to controls. While protein levels of the main hepatic bile acid transporters were unchanged, the rate-limiting enzyme in the bile acid synthesis, Cyp7a1, was significantly increased by EGCG. Enhanced bile acid synthesis in these animals was also confirmed by a 2-fold increase in plasma marker 7α-hydroxy-4-cholesten-3-one. In contrast, EGCG markedly downregulated major bile acid transporters (Asbt and Ostα) and regulatory molecules (Shp and Fgf15) in the ileum. When EGCG was coadministered with ethinylestradiol, a potent cholestatic agent, it did not show any additional effect on the induced cholestasis. This study shows ability of EGCG to raise plasma bile acid concentrations, mainly through Cyp7a1 upregulation, and to decrease bile production through reduction in Mrp2-mediated bile acid-independent bile flow. In conclusion, our data demonstrate that under certain conditions EGCG may induce cholestasis.
- MeSH
- ABC transportéry genetika MeSH
- cholestáza chemicky indukované MeSH
- cholestenony metabolismus MeSH
- cholesterol-7-alfa-hydroxylasa genetika metabolismus MeSH
- down regulace účinky léků MeSH
- ethinylestradiol farmakologie MeSH
- glutathion metabolismus MeSH
- hepatocyty účinky léků metabolismus MeSH
- homeostáza účinky léků MeSH
- ileum účinky léků metabolismus MeSH
- katechin analogy a deriváty toxicita MeSH
- krysa rodu rattus MeSH
- permeabilita MeSH
- potkani Wistar MeSH
- upregulace účinky léků MeSH
- žlučové kyseliny a soli biosyntéza metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Antiinflammatory effect of statins mediated by the reduction of cytokine IL-6 in hepatocytes have been reported. Contrary to beneficial effect, statins can increase susceptibility to mitochondrial dysfunction. Extrahepatic biliary obstruction is associated with oxidative stress, pro-inflammatory response and hepatocyte mitochondrial dysfunction. The aim of our study was to verify the effect of fluvastatin on cholestatic liver injury. Cholestasis was induced in Wistar rats by bile duct ligation. Fluvastatin (1 or 5 mg/kg) was administered after surgery and then daily for 7 days. The dose of 5 mg/kg led to the deterioration of hepatocellular injury. Despite lower production of IL-6, decrease in GSH content, rise of TGFß and inhibition of respiratory complex I in mitochondria were determined. The mRNA expressions of canalicular transporter Mdr1b and basolateral transporter Mrp3 increased in cholestatic liver. Fluvastatin administration then led to the attenuation of this change. Analogously, mRNA expression of conjugative enzyme Ugt1a1 was diminished by fluvastatin administration to cholestatic rats. We can conclude that decrease in the antioxidative status and mitochondrial dysfunction could at least in part participate on the deteriorating effect of fluvastatin. Whether these processes can be a consequence of the alteration in metabolism and transport of potentially toxic substances remains to verify.
- MeSH
- alanintransaminasa krev účinky léků metabolismus MeSH
- alkalická fosfatasa krev účinky léků metabolismus MeSH
- aspartátaminotransferasy krev účinky léků metabolismus MeSH
- bilirubin krev metabolismus MeSH
- gama-glutamyltransferasa krev účinky léků metabolismus MeSH
- glukuronosyltransferasa účinky léků metabolismus MeSH
- glutathion účinky léků metabolismus MeSH
- indoly škodlivé účinky MeSH
- interleukin-6 metabolismus MeSH
- intrahepatální cholestáza farmakoterapie metabolismus MeSH
- játra účinky léků patologie MeSH
- krysa rodu rattus MeSH
- kyseliny mastné mononenasycené škodlivé účinky MeSH
- ligace MeSH
- messenger RNA účinky léků metabolismus MeSH
- potkani Wistar MeSH
- statiny škodlivé účinky MeSH
- transformující růstový faktor beta účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We provide a detailed characteristic of stem cells isolated and expanded from the human dental pulp. Dental pulp stem cells express mesenchymal cell markers STRO-1, vimentin, CD29, CD44, CD73, CD90, CD166, and stem cell markers Sox2, nestin, and nucleostemin. They are multipotent as shown by their osteogenic and chondrogenic potential. We measured relative telomere length in 11 dental pulp stem cell lines at different passages by quantitative real-time PCR. Despite their large proliferative capacity, stable viability, phenotype, and genotype over prolonged cultivation, human dental pulp stem cells suffer from progressive telomere shortening over time they replicate in vitro. Relative telomere length (T/S) was inversely correlated with cumulative doubling time. Our findings indicate that excessive ex vivo expansion of adult stem cells should be reduced at minimum to avoid detrimental effects on telomere maintenance and measurement of telomere length should become a standard when certificating the status and replicative age of stem cells prior therapeutic applications.
- MeSH
- analýza kolonii tvořících jednotek MeSH
- časové faktory MeSH
- CD antigeny metabolismus MeSH
- chondrogeneze MeSH
- DNA MeSH
- dospělí MeSH
- imunohistochemie MeSH
- kinetika MeSH
- kmenové buňky cytologie metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikroskopie fázově kontrastní MeSH
- mladiství MeSH
- mladý dospělý MeSH
- multipotentní kmenové buňky cytologie metabolismus MeSH
- osteogeneze MeSH
- počet buněk MeSH
- proliferace buněk MeSH
- průtoková cytometrie MeSH
- referenční standardy MeSH
- telomery patologie MeSH
- zubní dřeň cytologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
