Chloroquine Intervenes Nephrotoxicity of Nilotinib through Deubiquitinase USP13-Mediated Stabilization of Bcl-XL.

ABSTRACT: Nephrotoxicity has become prominent due to the increase in the clinical use of nilotinib, a second-generation BCR-ABL1 inhibitor in the first-line treatment of Philadelphia chromosome-positive chronic myeloid leukemia. To date, the mechanism of nilotinib nephrotoxicity is still unknown, leading to a lack of clinical intervention strategies. Here, it is found that nilotinib could induce glomerular atrophy, renal tubular degeneration, and kidney fibrosis in an animal model. Mechanistically, nilotinib induces intrinsic apoptosis by specifically reducing the level of BCL2 like 1 (Bcl-XL) in both vascular endothelial cells and renal tubular epithelial cells, as well as in vivo. It is confirmed that chloroquine (CQ) intervenes with nilotinib-induced apoptosis and improves mitochondrial integrity

SUBMITTER: Yan H 

PROVIDER: S-EPMC10502815 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature