- MeSH
- ascites etiologie MeSH
- dospělí MeSH
- extrahepatální cholestáza etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci žlučových cest * diagnóza patofyziologie MeSH
- počítačová rentgenová tomografie MeSH
- portální systém * patofyziologie patologie MeSH
- splenomegalie etiologie MeSH
- ultrasonografie dopplerovská MeSH
- žilní trombóza * radiografie MeSH
- žlučové cesty patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
OBJECTIVES: The present study was aimed at evaluation of in vivo biliary and renal excretion of rhodamine 123 (Rho123), a P-glycoprotein (P-gp) substrate, in rats during either acute or chronic cholestasis induced by bile duct obstruction (BDO). METHODS: The Rho123 clearance study was performed either one (BDO1) or seven (BDO7) days after BDO. Bile flow was reconstituted, and bile and urine were collected after steady-state plasma concentration of Rho123 was attained. Tissue expression of P-gp was evaluated by quantitative immunohistochemistry, and immunoblotting. RESULTS: Significant up-regulation of the liver P-gp protein was observed in acute and chronic cholestasis. Primary periportal location of P-gp was enlarged also to pericentral areas. In the kidneys, immunohistochemistry showed pancellular increase in P-gp after 1 day of BDO, which subsided after 7 days of BDO. Nevertheless, biliary and renal clearances (CL(Bile) and CL(R)) of Rho123 did not reflect the induction of P-gp expression. While CL(Bile) was reduced one day after cholestasis and restored on the seventh day, the CL(R) was preserved in BDO1 group and reduced in BDO7 group without change in glomerular filtration rate. In parallel, biliary and renal clearances of conjugated bilirubin were significantly reduced in both cholestatic groups compared with controls. CONCLUSION: These findings suggest that extrahepatic cholestasis causes time-dependent changes in elimination of Rho123 which do not exactly reflect alteration of P-gp expression in the rat liver and kidney. These data may help to explain impaired elimination of P-gp substrates after short-term cholestasis that may commonly occur in clinical practice.
- MeSH
- akutní nemoc MeSH
- bilirubin metabolismus MeSH
- chronická nemoc MeSH
- extrahepatální cholestáza etiologie metabolismus MeSH
- financování organizované MeSH
- fluorescenční barviva diagnostické užití MeSH
- krysa rodu rattus MeSH
- ledviny metabolismus MeSH
- modely nemocí na zvířatech MeSH
- P-glykoproteiny fyziologie metabolismus MeSH
- potkani Wistar MeSH
- rhodamin 123 diagnostické užití MeSH
- western blotting MeSH
- žluč metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
