Protective Effects of Quercetin Against Vincristine-Induced Nephrotoxicity Via Modulation of Oxidative Stress, Inflammation, and Apoptosis in Rats

Abstract

Vincristine is a widely used chemotherapeutic agent in pediatric leukemias and solid tumors, but the use of this chemotherapeutic agent is associated with many organ damages, especially nephrotoxicity. Quercetin, a natural flavonoid, is known for its antioxidant and anti-inflammatory potential. Vincristine was intraperitoneally administered at a dose of 0.1 mg/kg body weight, and quercetin was orally administered at doses of 25 and 50 mg/kg body weight. Both treatments were applied to the rats on days 1-6 and 9-14. Renal function was assessed via serum urea and creatinine levels. Oxidative stress and lipid peroxidation were evaluated by measuring GSH, SOD, CAT, GPx, and MDA. The mRNA levels of apoptotic markers such as p53, Bax, Bcl-2, Jnk and Beclin-1 and inflammatory markers such as TNF-alpha, IL-1 beta, COX-2, and PGE-2 were analyzed by RT-qPCR. The HO-1, Nrf2, PGC-1 alpha and SIRT1, NF kappa B and STAT3 protein levels were determined by ELISA. In addition, the protein levels of PI3K and AKT in survival pathways were analyzed using the Western blot method. The results showed that vincristine significantly impaired renal function by increasing oxidative stress, inflammation, and apoptosis. Quercetin protected renal function by enhancing antioxidant defense, reducing inflammatory signals and reversing apoptosis. The findings reveal that quercetin exhibits protective effects against vincristine-induced nephrotoxicity through antioxidant, anti-inflammatory and antiapoptotic mechanisms.