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

• DOI: 10.1002/advs.202302002
• Publication Date: 2023-07-15T03:16:45Z
• Authors: Hao Yan; Xiangliang Huang; Jiangxin Xu; Ying Zhang; Jiajia Chen; Zhifei Xu; Hui Li; Zeng Wang; Xiaochun Yang; Bo Yang; Qiaojun He; Peihua Luo
• Keywords: Nephrotoxicity

Abstract Nephrotoxicity has become prominent due to the increase in clinical use of nilotinib, a second‐generation BCR‐ABL1 inhibitor first‐line treatment Philadelphia chromosome‐positive chronic myeloid leukemia. To date, mechanism nilotinib nephrotoxicity is still unknown, leading lack intervention strategies. Here, it found that could induce glomerular atrophy, renal tubular degeneration, and kidney fibrosis an animal model. Mechanistically, induces intrinsic apoptosis by specifically reducing level BCL2 like 1 (Bcl‐XL) both vascular endothelial cells epithelial cells, as well vivo. It confirmed chloroquine (CQ) intervenes with nilotinib‐induced improves mitochondrial integrity, reactive oxygen species accumulation, DNA damage reversing decreased Bcl‐XL. The effect dependent on alleviation reduction ubiquitin specific peptidase 13 (USP13) does not rely autophagy inhibition. Additionally, USP13 abrogates cell preventing excessive ubiquitin‒proteasome degradation In conclusion, research reveals molecular nilotinib's nephrotoxicity, highlighting important regulator Bcl‐XL stability determining fate, provides CQ analogs strategy for nephrotoxicity.