An oral sorbent, AST-120, increases Klotho expression and inhibits cell senescence in the kidney of uremic rats.
OBJECTIVE
Klotho, an anti-aging gene, is primarily expressed in the kidney, and its renal expression is decreased in chronic renal failure (CRF). We determined if administration of an oral sorbent, AST-120, increases the expression of Klotho, and inhibits cell senescence in the kidney of CRF rats.


METHODS
CRF rats were produced by 4/5-nephrectomy. AST-120 was administered to the CRF rats at a dose of 4 g/kg with powder chow for 16 weeks, whereas powder chow alone was administered to control CRF rats. The expression of Klotho and cell senescence (senescence-associated beta-galactosidase: SA-beta-gal) was detected by immunohistochemistry.


RESULTS
The expression of Klotho was significantly decreased in the kidney of CRF rats as compared with normal rats. AST-120-treated CRF rats showed significantly increased renal expression of Klotho as compared with CRF rats. The expression of SA-beta-gal was significantly increased in the kidney of CRF rats as compared with normal rats. AST-120-treated CRF rats showed significantly decreased expression of SA-beta-gal in the kidney as compared with CRF rats. AST-120 significantly decreased serum and urine levels of indoxyl sulfate.


CONCLUSIONS
AST-120 increased Klotho expression, and inhibited cell senescence in the kidney of CRF rats, probably by alleviating indoxyl sulfate overload on the kidney.
Adijiang
Ayinuer
A
Clinical Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan.
Niwa
Toshimitsu
T
D000818:Animals; D002244:Carbon / Q000494:pharmacology*; D016922:Cellular Senescence; D005966:Glucuronidase / Q000096:biosynthesis*; D007150:Immunohistochemistry / Q000379:methods; D007200:Indican / Q000737:chemistry; D007668:Kidney / Q000378:metabolism; D000090265:Klotho Proteins; D008297:Male; D009154:Mutation; D010087:Oxides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000188:drug therapy; D013997:Time Factors; D014511:Uremia / Q000378:metabolism / Q000473:pathology*
D010087:Oxides; D002244:Carbon; C040896:AST 120; D005966:Glucuronidase; D000090265:Klotho Proteins; D007200:Indican