An Oral Sorbent, AST-120, Increases Klotho Expression and Inhibits Cell Senescence in the Kidney of Uremic Rats

Abstract

Background/Aim: 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 β-galactosidase: SA-β-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-β-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-β-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.