Effects of Chemotherapeutic Agents (5-Fluorouracil, Cisplatin and Methotrexate) on Cell Adhesion Molecules and Oxidative Damage Markers in Rat Kidney Tissue.

Abstract

Chemotherapeutic drugs are widely used in cancer treatment; however, their limited selectivity often causes toxicity in nontarget organs, particularly the kidneys. The relationship between chemotherapy-induced oxidative stress and cell adhesion mechanisms in renal tissue remains poorly understood. Therefore, this study investigated the effects of three commonly used chemotherapeutic agents-5-fluorouracil (5-FU), cisplatin (CIS) and methotrexate (MTX) on oxidative stress biomarkers and adhesion-related proteins in rat kidney tissue. Twenty male Sprague-Dawley rats were randomly assigned to four groups: control, 5-FU (200 mg/kg), CIS (10 mg/kg) and MTX (50 mg/kg). Kidney samples were collected 24 h after administration under ketamine-xylazine anaesthesia. Tissue levels of 8-OHdG, NO, ADA, GSH and MDA were determined. Protein expression of E-selectin, caspase-3 and β1-integrin in kidney tissue was evaluated using Western blotting. All treatment groups showed increased levels of 8-OHdG, NO, ADA and MDA in kidney tissue, whereas GSH levels were reduced. The highest oxidative damage was observed in the CIS group. Western blot results demonstrated increased expression of E-selectin, caspase-3, and β1-integrin, with strongest increases detected in the MTX group. These findings indicate that 5-FU, CIS and MTX induce oxidative stress, DNA damage and alterations in apoptosis- and adhesion-related pathways in renal tissue, suggesting drug-specific mechanisms underlying chemotherapy-associated nephrotoxicity.