Spherical carbon adsorbent (AST-120) protects deterioration of renal function in chronic kidney disease rats through inhibition of reactive oxygen species production from mitochondria and reduction of serum lipid peroxidation

Nephron Exp Nephrol. 2010;115(4):e101-11. doi: 10.1159/000313491. Epub 2010 Apr 28.

Abstract

Background/aim: An imbalance in renal redox status contributes to progression of renal dysfunction. We investigated the effects of an oral charcoal adsorbent (AST-120) on renal redox status, superoxide production from renal mitochondria, and serum lipid peroxidation using chronic kidney disease (CKD) model rats.

Methods: CKD was induced by 5/6 nephrectomy. CKD rats were divided into 2 groups: controls, and those treated with AST-120 for 20 weeks. We evaluated: (1) renal redox status by in vivo low-frequency electron spin resonance imaging (EPRI); (2) renal superoxide scavenging activity (SSA); (3) superoxide production from renal mitochondria; (4) immunostaining for Cu-Zn superoxide dismutase (SOD), and (5) oxidative stress markers including LDL-negative charge (LDL-CMF), serum lipid peroxide (LPO) and urinary hexanoyl-lysine (HEL). The effect of indoxyl sulfate, a uremic toxin, on mitochondrial superoxide production was also investigated.

Results: AST-120 treatment improved renal function, renal SSA, renal mitochondrial superoxide production, renal SOD expression, renal redox status by EPRI, and oxidative stress profiles by LDL-CMF, LPO and urinary HEL. Addition of indoxyl sulfate increased mitochondrial superoxide production and AST-120 also decreased this.

Conclusions: Improvements in the redox status and lipid peroxidation induced by AST-120 may delay the progression of CKD.

MeSH terms

  • Adsorption
  • Animals
  • Carbon / therapeutic use*
  • Creatinine / blood
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / prevention & control*
  • Lipid Peroxidation / drug effects*
  • Lipids / blood
  • Male
  • Microspheres
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects
  • Oxides / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / metabolism

Substances

  • Lipids
  • Oxides
  • Reactive Oxygen Species
  • Carbon
  • AST 120
  • Creatinine
  • Superoxide Dismutase