Biological Role of Pazopanib and Sunitinib Aldehyde Derivatives in Drug-Induced Liver Injury.

ABSTRACT: Tyrosine kinase inhibitors pazopanib and sunitinib are both used to treat advanced renal cell carcinoma but expose patients to an increased risk of hepatotoxicity. We have previously identified two aldehyde derivatives for pazopanib and sunitinib (P-CHO and S-CHO, respectively) in liver microsomes. In this study, we aimed to decipher their role in hepatotoxicity by treating HepG2 and HepaRG hepatic cell lines with these derivatives and evaluating cell viability, mitochondrial dysfunction, and oxidative stress accumulation. Additionally, plasma concentrations of P-CHO were assessed in a cohort of patients treated with pazopanib. Results showed that S-CHO slightly decreased the viability of HepG2, but to a lesser extent than sunitinib, and affected the maximal respiratory capacity of the mit

SUBMITTER: Maillard M 

PROVIDER: S-EPMC9505977 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature