Berberine protects against gefitinib-induced liver injury by inhibiting the HMGB1/TLR4/NF-κB pathway.

ABSTRACT:

Background

Gefitinib (GEF), a first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for non-small cell lung cancer (NSCLC), is frequently associated with drug-induced liver injury (DILI), thereby limiting its clinical application. This study aimed to evaluate the hepatoprotective effects of berberine (BBR) and explore the underlying mechanisms.

Methods

In vitro, human hepatocyte lines (THLE-2 and THLE-3) were exposed to GEF alone or in combination with HMGB1 siRNA, a TLR4 inhibitor, an NF-κB inhibitor, or varying concentrations of BBR to assess hepatotoxicity and the involvement of the HMGB1/TLR4/NF-κB pathway. In vivo, Sprague-Dawley (SD) rats were treated with GEF with or without different doses of BBR for 21 days. Liver inj

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC12417729 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature