Effect of Selenium on Cisplatin-Induced Nephrotoxicity in Rats

Abstract

Cisplatin (CP), a commonly used antineoplastic drug, is nephrotoxic. CP-induced nephrotoxicity involves oxidative pathways. A deficiency of selenium (Se) reduces glutathione peroxidase (GPx) activity resulting in oxidative stress. We investigated how Se deficiency or oral Se administration influences CP-induced nephrotoxicity. Thirty male Wistar rats were fed a Se-deficient or control diet for 4 weeks. Then they were given intraperitoneal (i.p.) CP alone, i.p. saline alone, or Se by gavage 24 and 1 h prior to i.p. CP. Blood and urine samples were collected and the kidneys were removed 5 days after CP treatment. Urinalysis, renal function, GPx activity, and expression of cellular GPx mRNA were measured. Histology was evaluated by light microscopy with immunohistochemistry for 4-hydroxy-2-nonenal (HNE), vimentin, and heme oxygenase (HO)-1. CP induced renal tubular damage with increased expression of vimentin, HO-1 and HNE staining, which represents lipid peroxidation. Se deficiency exacerbated CP-induced nephrotoxicity as shown by deterioration of the above parameters and depressed GPx activity and expression of GPx mRNA. Se treatment ameliorated CP-induced nephrotoxicity, but did not significantly improve renal function. These findings suggest that Se deficiency increases oxidative stress and enhances CP-induced nephrotoxicity, whereas oral Se treatment partially protects against the nephrotoxicity in rats.