Impaired clearance of sunitinib leads to metabolic disorders and hepatotoxicity.

ABSTRACT:

Background and purpose

Sunitinib is a small-molecule TK inhibitor associated with hepatotoxicity. The mechanisms of its toxicity are still unclear.

Experimental approach

In the present study, mice were treated with 60, 150, and 450 mg·kg^-1 sunitinib to evaluate sunitinib hepatotoxicity. Sunitinib metabolites and endogenous metabolites in liver, serum, faeces, and urine were analysed using ultra-performance LC electrospray ionization quadrupole time-of-flight MS-based metabolomics.

Key results

Four reactive metabolites and impaired clearance of sunitinib in liver played a dominant role in sunitinib-induced hepatotoxicity. Using a non-targeted metabolomics approach, various metabolic pathways, including mitochondrial fatty acid β-oxidation (β-FAO), bile acids

SUBMITTER: Zhao Q 

PROVIDER: S-EPMC6555861 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature