Spherical carbon adsorbent (AST-120) protects deterioration of renal function in chronic kidney disease rats through inhibition of reactive oxygen species production from mitochondria and reduction of serum lipid peroxidation.
OBJECTIVE
An imbalance in renal redox status contributes to progression of renal dysfunction. We investigated the effects of an oral charcoal adsorbent (AST-120) on renal redox status, superoxide production from renal mitochondria, and serum lipid peroxidation using chronic kidney disease (CKD) model rats.


METHODS
CKD was induced by 5/6 nephrectomy. CKD rats were divided into 2 groups: controls, and those treated with AST-120 for 20 weeks. We evaluated: (1) renal redox status by in vivo low-frequency electron spin resonance imaging (EPRI); (2) renal superoxide scavenging activity (SSA); (3) superoxide production from renal mitochondria; (4) immunostaining for Cu-Zn superoxide dismutase (SOD), and (5) oxidative stress markers including LDL-negative charge (LDL-CMF), serum lipid peroxide (LPO) and urinary hexanoyl-lysine (HEL). The effect of indoxyl sulfate, a uremic toxin, on mitochondrial superoxide production was also investigated.


RESULTS
AST-120 treatment improved renal function, renal SSA, renal mitochondrial superoxide production, renal SOD expression, renal redox status by EPRI, and oxidative stress profiles by LDL-CMF, LPO and urinary HEL. Addition of indoxyl sulfate increased mitochondrial superoxide production and AST-120 also decreased this.


CONCLUSIONS
Improvements in the redox status and lipid peroxidation induced by AST-120 may delay the progression of CKD.
Owada
Shigeru
S
Dialysis Unit, Asao Clinic, Kanagawa, Japan. s2oowada@nifty.com
Maeba
Teruhiko
T
Sugano
Yasuji
Y
Hirayama
Aki
A
Ueda
Atsushi
A
Nagase
Sohji
S
Goto
Sumie
S
Nishijima
Fuyuhiko
F
Bannai
Kenji
K
Yamato
Hideyuki
H
D000327:Adsorption; D000818:Animals; D002244:Carbon / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008297:Male; D008863:Microspheres; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D008055:Lipids; D010087:Oxides; D017382:Reactive Oxygen Species; D002244:Carbon; C040896:AST 120; D003404:Creatinine; D013482:Superoxide Dismutase