Neutrophil-dependent hepatic platelet accumulation and liver injury revealed by acetaminophen dose-response studies.

ABSTRACT:

Background

Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure (ALF). Neutrophil activation has been associated with poor outcomes in patients with ALF and is proposed to amplify coagulation in this context. However, the precise role of neutrophils in APAP-induced liver injury is not known.

Methods

We used a dual antibody-mediated neutrophil depletion strategy to determine the role of neutrophils in mice challenged with different doses of APAP (300 or 600 mg/kg) that produce hepatotoxicity and ALF-like pathology.

Results

Flow cytometry confirmed depletion of neutrophils in whole blood prior to APAP challenge. Mice given isotype control and challenged with 300 mg/kg APAP developed marked hepatocellular necrosis and showed an increase in

SUBMITTER: Schulte A 

PROVIDER: S-EPMC10883821 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature