New molecular insights into the mechanisms of cholestasis

Abstract

Recent progress in basic research has enhanced our understanding of the molecular mechanisms of normal bile secretion and their alterations in cholestasis. Genetic transporter variants contribute to an entire spectrum of cholestatic liver diseases and can cause hereditary cholestatic syndromes or determine susceptibility and disease progression in acquired cholestatic disorders. Cholestasis is associated with complex transcriptional and post-transcriptional alterations of hepatobiliary transporters and enzymes participating in bile formation. Ligand-activated nuclear receptors for bile acids and other biliary compounds play a key role in the regulation of genes required for bile formation. Pharmacological interventions in cholestasis may aim at modulating such novel regulatory pathways. This review will summarize the principles of molecular alterations in cholestasis and will give an overview of potential clinical implications.

Hyperbilirubinemia with Urinary Tract Infection in Infants Younger Than Eight Weeks Old

“…Pro inflammatory cytokines can either reduce transporter gene expression or directly inhibit transport protein function [16].…”

In vivo imaging of hepatic excretory function in the rat by fluorescence microscopy

“…In both hereditary and acquired cholestatic liver diseases (e.g. alcoholic hepatitis or liver cirrhosis), this is associated with an accumulation of potentially toxic substances in the liver and the systemic circulation [1].…”

“…Animal models for investigation of the pathophysiology of cholestasis have been successfully developed [1], but only few techniques for in vivo imaging of hepatobiliary excretory function have been reported so far [2][3][4]. Recently, Lee et al presented a technique for visualization of hepatic excretory function and its application in an animal model for obstructive cholestasis by multiphoton fluorescence microscopy and carboxyfluorescein diacetate (CFDA) [3,5].…”

Protective effects of ginseng total saponins against hepatic ischemia/reperfusion injury in experimental obstructive jaundice rats

“…To prevent blood loss, liver surgery usually requires temporary warm ischemia by inflow control (the Pringle maneuver) or combined inflow and outflow occlusion. After restoring the blood supply, the liver is further susceptible to ischemia/ reperfusion (IR) injury (Wagner et al, 2009;Yoshidome et al, 2000). Fast-track surgery (FTS) as a set of protocols has been implemented in most hospitals to enhance recovery after surgery.…”