Oral sorbent AST-120 increases renal NO synthesis in uremic rats.
OBJECTIVE
The urine level of nitric oxide (NO) metabolites, i.e., nitrates/nitrites (NOx), in chronic renal failure (CRF) is decreased because of reduced renal synthesis of NO. We determined whether the administration of an oral sorbent, AST-120, increases the urine level of NOx and the renal expression of nitric oxide synthase (NOS) isoforms in CRF rats.


METHODS
Chronic renal failure rats were produced by 4/5 nephrectomy. Rats were randomized into two groups: CRF control rats, and AST-120-treated CRF rats. The AST-120 was administered to the rats at a dose of 4 g/kg with powder chow for 16 weeks, whereas powder chow alone was administered to control rats. The urine levels of NOx were measured by using a NOx colorimetric assay kit. The expression of endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) in the kidney was determined by immunohistochemistry. Serum and urine levels of indoxyl sulfate were determined by high-performance liquid chromatography.


RESULTS
Urine levels of NOx and the expression of glomerular eNOS and tubulointerstitial nNOS were significantly decreased in CRF rats compared with normal rats. The administration of AST-120 to CRF rats significantly increased urine levels of NOx and the expression of glomerular eNOS and tubulointerstitial nNOS. The administration of AST-120 to CRF rats significantly decreased urine and serum levels of indoxyl sulfate.


CONCLUSIONS
The oral sorbent AST-120 increases NO synthesis in the kidneys of uremic rats by increasing the renal expression of eNOS and nNOS, through alleviation of indoxyl sulfate overload on the kidney.
Tumur
Zohra
Z
Department of Clinical Preventive Medicine, Nagoya University Hospital, Nagoya, Japan.
Niwa
Toshimitsu
T
D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight; D002244:Carbon / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D007200:Indican / Q000097:blood / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009392:Nephrectomy; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014511:Uremia / Q000378:metabolism*
D010087:Oxides; D009569:Nitric Oxide; D002244:Carbon; C040896:AST 120; D003404:Creatinine; D052250:Nitric Oxide Synthase Type III; D007200:Indican