Protective activity of selenium against 5-fluorouracil-induced nephrotoxicity in rats

Abstract

Background: The nephrotoxic effect of 5-fluorouracil (5-FU) involves alterations in renal function markers and kidney morphology. This study assessed the protective effect of selenium (Se) on 5-FU-induced alterations in renal function markers and kidney morphology in albino rats. Materials and Methods: Forty adult albino rats of (n = 5) used were randomly grouped. Groups B-D received 0.125 mg/kg, 0.25 mg/kg and 0.50 mg/kg of Se intraperitoneally (ip) daily for 5 days, respectively. Group E received 20 mg/kg of 5-FU ip daily for 5 days. Groups F-H received 0.125 mg/kg, 0.25 mg/kg, and 0.5 mg/kg of Se before receiving 20 mg/kg of 5-FU ip daily for 5 days, respectively. Group A (Control) received 0.2 mL of normal saline ip daily for 5 days. Rats were sacrificed on the 6th day, and blood samples were collected and evaluated for markers of serum renal function. Kidneys were assessed for oxidative stress indices and histology. Results: The nephrotoxic effect of 5-FU was characterized by statistically significant (P < 0.001) elevations in creatinine, urea, uric acid, and malondialdehyde levels in comparison to control. Furthermore, significant (P < 0.001) decreases in potassium, sodium, chloride, bicarbonate, glutathione (GSH), catalase, superoxide dismutase, and GSH peroxidase levels were obtained in 5-FU-treated rats in comparison to control. Necroses of kidney tubular epithelial cells and atrophic glomeruli were observed in rats administered with 5-FU. However, 5-FU-induced nephrotoxic changes were significantly downregulated in a dose-dependent fashion in rats supplemented with 0.125 mg/kg (P < 0.05), 0.25 mg/kg (P < 0.01), and 0.50 mg/kg (P < 0.001) of Se when compared to 5-FU treated rats. Conclusion: Supplementation with Se may have clinical benefit in nephrotoxicity caused by 5-FU.