Interruption of bile acid uptake by hepatocytes after acetaminophen overdose ameliorates hepatotoxicity.

ABSTRACT:

Background & aims

Acetaminophen (APAP) overdose remains a frequent cause of acute liver failure, which is generally accompanied by increased levels of serum bile acids (BAs). However, the pathophysiological role of BAs remains elusive. Herein, we investigated the role of BAs in APAP-induced hepatotoxicity.

Methods

We performed intravital imaging to investigate BA transport in mice, quantified endogenous BA concentrations in the serum of mice and patients with APAP overdose, analyzed liver tissue and bile by mass spectrometry and MALDI-mass spectrometry imaging, assessed the integrity of the blood-bile barrier and the role of oxidative stress by immunostaining of tight junction proteins and intravital imaging of fluorescent markers, identified the intracellular cytotoxic conc

SUBMITTER: Ghallab A 

PROVIDER: S-EPMC9209783 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature