Indoxyl sulfate reduces superoxide scavenging activity in the kidneys of normal and uremic rats.
OBJECTIVE
Indoxyl sulfate (IS) is a uremic toxin that accelerates the progression of chronic renal failure (CRF). This study aimed at determining whether IS impairs antioxidative systems (redox status) in the kidney.


METHODS
IS was orally administered to normal and subtotally nephrectomized (three fourths and five sixths) rats (CRF rats) for 2 weeks. By use of in vivo and ex vivo electron spin resonance spectroscopy, the kidney redox status was evaluated using carbamoyl-PROXYL as a radical spin probe in living rats, and the kidney superoxide scavenging activity was measured. Immunohistochemistry of superoxide dismutase (SOD) in the kidney was performed.


RESULTS
Administration of IS increased serum and kidney levels of IS and serum creatinine and decreased creatinine clearance. CRF rats showed reduced spin reduction rate, prolonged half-life of the spin probe, and reduced superoxide scavenging activity and SOD-positive areas in the kidney as compared with normal rats. Administration of IS further reduced radical spin reduction rate, prolonged half-life of the spin probe, and reduced superoxide scavenging activity and SOD-positive areas in the kidneys.


CONCLUSIONS
Administration of IS reduced superoxide scavenging activity in the kidneys of normal and CRF rats. Thus, the nephrotoxicity of IS may be induced by impairing the antioxidative systems in the kidney.
Owada
Shigeru
S
Dialysis Unit, Asao Clinic, Kawasaki, Japan.
Goto
Sumie
S
Bannai
Kenji
K
Hayashi
Hideo
H
Nishijima
Fuyuhiko
F
Niwa
Toshimitsu
T
D000818:Animals; D016022:Case-Control Studies; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000378:metabolism*; D006207:Half-Life; D007150:Immunohistochemistry; D007200:Indican / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D011759:Pyrrolidines; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism
C499782:3-carboxy-2,2,5,5-tetramethylpyrrolidin-1-yloxyl; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D011759:Pyrrolidines; D013481:Superoxides; D013482:Superoxide Dismutase; D007200:Indican