Naringenin Mitigates Dasatinib-Induced Kidney Damage by Modulating Antioxidant Defense, Inflammation, and Apoptosis Pathways

Nephrotoxicity remains a significant concern associated with tyrosine kinase inhibitors, such as dasatinib (DASA). Previous studies have shown that DASA can induce renal tubular cell death, contributing to its nephrotoxic effects. In contrast, naringenin (NGN) is known for its antioxidant and anti-inflammatory properties. This study aimed to explore the nephroprotective potential of NGN against acute kidney injury induced by DASA in a mouse model. Mice were pre-treated with different doses of NGN (50, 100 mg/kg) for one week, followed by a single dose of DASA (25 mg/kg) on the 8th day. Results demonstrated that DASA significantly increased serum levels of blood urea nitrogen, creatinine, uric acid, and Lactate Dehydrogenase, which were effectively attenuated by NGN pretreatment. Furthermore, kidney tissues exposed to DASA exhibited elevated malondialdehyde (MDA) levels, which were significantly reduced by NGN. NGN also restored depleted levels of Antioxidants (glutathione (GSH) and catalase (CAT)) in kidney tissues following DASA treatment. Additionally, NGN mitigated the upregulation of pro-inflammatory cytokines (TNF-α, NF-κB, and IL-6) induced by DASA, indicating an anti-inflammatory effect. Notably, DASA treatment upregulated the gene expression of the pro-apoptotic gene Bax while downregulating the expression of Bcl-2 and Caspase-3 in kidney tissues. These findings suggest that NGN exerts nephroprotective effects against DASA-induced nephrotoxicity through its antioxidant, anti-inflammatory, and anti-apoptotic properties. Further investigations are warranted to elucidate the underlying mechanisms involved.

Apoptosis; Dasatinib; Inflammation; Naringenin; Nephrotoxicity; Oxidative stress.