Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity.

ABSTRACT:

Introduction

Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis.

Aim

To investigate the mechanisms that underlie the hormetic response that protect hepatocytes against experimental cholestatic conditions.

Methods

HepG2.rNtcp cells were preconditioned (24 h) with sub-apoptotic concentrations (0.1-50 μM) of various bile acids, the superoxide donor menadione, TNF-α or the Farsenoid X Receptor agonist GW4064, followed by a challenge with the apo

SUBMITTER: Verhaag EM 

PROVIDER: S-EPMC4780766 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature