Abstract
Bile formation is markedly impaired during cholestasis. Consequently, hepatic and further systemic accumulation of toxic biliary constituents, occurs.
In an effort to compensate this situation, spontaneous anti-cholestatic mechanisms are activated, which provide alternative excretory routes for accumulating compounds. These mechanisms include changes in the expression, localization and function of respective transporters in liver and kidneys.
Another mechanism with a significant impact on bile formation and transport of compounds between bile and blood is blood-biliary barrier formed by tight-junctions and gap-junctions. In this work both mechanisms responsible for bile formation and secretion - transporters and blood-biliary barrier - were studied.
Next, acute and chronic cholestasis induced changes in transporter expression and integrity of blood-biliary barrier were evaluated. In addition, changes in PK of drugs, acting as substrates of selected transporters, were examined, too.