Effect of selenium on Cisplatin-induced nephrotoxicity in rats.
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.
Fujieda
Mikiya
M
Department of Pediatrics, Kochi Medical School, Kochi University, Nankoku, Japan. fujiedam@med.kochi-u.ac.jp
Naruse
Keishi
K
Hamauzu
Tadashi
T
Miyazaki
Eriko
E
Hayashi
Yoshihiro
Y
Enomoto
Riyo
R
Lee
Eibai
E
Ohta
Kazuhide
K
Wakiguchi
Hiroshi
H
Enzan
Hideaki
H
D000284:Administration, Oral; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D002945:Cisplatin; D019610:Cytoprotection; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology*; D014746:Vimentin / Q000378:metabolism
D000447:Aldehydes; D000975:Antioxidants; D012333:RNA, Messenger; D014746:Vimentin; C462359:tert-4-hydroxy-2-nonenal; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D012643:Selenium; D002945:Cisplatin