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An oral sorbent, AST-120, increases Klotho expression and inhibits cell senescence in the kidney of uremic rats.

American journal of nephrology

pathology, metabolism, Uremia, Time Factors, drug therapy, Renal Insufficiency, Rats, Sprague-Dawley, Rats, pharmacology, Oxides, Mutation, Male, Kidney, chemistry, Indican, methods, Immunohistochemistry, biosynthesis, Glucuronidase, Cell Aging, Carbon, Animals

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      Abstract

      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. 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. 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. AST-120 increased Klotho expression, and inhibited cell senescence in the kidney of CRF rats, probably by alleviating indoxyl sulfate overload on the kidney. Copyright (c) 2009 S. Karger AG, Basel.

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      Journal
      10.1159/000264634
      19955715

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