An oral adsorbent, AST-120, suppresses oxidative stress in uremic rats.
BACKGROUND
The production of reactive oxygen species (ROS) has been suggested to play an important role in the progression of chronic kidney disease (CKD). An oral adsorbent, AST-120, removes uremic toxins such as indoxyl sulfate (IS) and delays the progression of CKD, but the effect on ROS production is unknown. The present study aimed to determine whether AST-120 reduces oxidative stress in uremic rat kidneys using markers of ROS production such as acrolein and 8-hydroxy-2'-deoxyguanosine (8-OHdG).


METHODS
Daily administration of AST-120 was started 6 weeks after 5/6 nephrectomy and continued for 18 weeks. The changes in metabolic data, serum and urine IS levels, urinary excretion of markers of oxidative stress, and renal histological findings were investigated in uremic rats with or without AST-120 treatment.


RESULTS
In parallel with the increase in serum and urine IS, the serum creatinine, urinary protein and acrolein levels started to increase at 6 weeks, but urinary 8-OHdG remained unchanged and significantly increased at 18 weeks in uremic rats. AST-120 markedly and significantly attenuated increases in uremic toxins and oxidative stress levels as well as the histological changes in glomerular sclerosis, interstitial fibrosis, and the tubular staining of 8-OHdG.


CONCLUSIONS
AST-120 suppressed the progression of CKD, at least in part, via attenuation of oxidative stress induced by uremic toxin.
Nakagawa
Naoki
N
Cardiovascular Division, Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan.
Hasebe
Naoyuki
N
Sumitomo
Kazuhiro
K
Fujino
Takayuki
T
Fukuzawa
Jun
J
Hirayama
Tomoya
T
Kikuchi
Kenjiro
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000171:Acrolein / Q000652:urine; D000327:Adsorption; D000818:Animals; D002244:Carbon / Q000008:administration & dosage / Q000494:pharmacology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine
D010087:Oxides; D002244:Carbon; D000171:Acrolein; D000080242:8-Hydroxy-2'-Deoxyguanosine; C040896:AST 120; D003849:Deoxyguanosine