title: Oral charcoal adsorbent (AST-120) prevents progression of cardiac damage in chronic kidney disease through suppression of oxidative stress.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease (CVD). Increased oxidative stress plays a role in the pathogenesis of CVD in CKD patients. The oral charcoal adsorbent AST-120 attenuates the progression of CKD possibly by removing uraemic toxins such as indoxyl sulfate (IS), and reduces oxidative stress. We investigated the relationship between oxidative stress and cardiac damage in CKD and its prevention by AST-120.
  
  
  METHODS
  Male Lewis rats were administered adriamycin at 8 weeks of age, and the right kidney was removed at 12 weeks of age. From 14 weeks of age, the rats were treated daily with AST-120 (n = 8) or were untreated (control group, n = 8). At 34 weeks of age, the rats were killed and urinary and blood biochemical tests as well as cardiac histological analyses were performed.
  
  
  RESULTS
  At 14 weeks of age, there were no significant differences in blood pressure, renal function (creatinine clearance: 1.54 +/- 0.28 mL/min versus 1.60 +/- 0.22 mL/min), oxidative stress markers or other biochemical data between the control and AST-120 groups. At 34 weeks, despite similar blood pressure and renal function (creatinine clearance: 0.78 +/- 0.46 mL/min versus 0.75 +/- 0.54 mL/min), serum concentrations of IS and urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), acrolein and IS were significantly lower in the AST-120 group than in the control group. Heart volume, left ventricular volume and cardiac fibrosis were significantly smaller in the experimental AST-120 group than in the control group. Immunohistological analysis revealed that the numbers of 8-OHdG- and acrolein-positive cardiomyocytes and the degrees of myocardial and perivascular fibrosis were ameliorated by AST-120 administration. The myocardial fibrosis score was significantly associated with the 8-OHdG- (r = 0.848, P < 0.001) and acrolein-positive (r = 0.812, P < 0.001) cell scores. The perivascular fibrosis score was also significantly associated with the 8-OHdG- (r = 0.906, P < 0.0001) and acrolein-positive (r = 0.789, P < 0.001) cell scores.
  
  
  CONCLUSIONS
  Oxidative stress is suggested to play a key role in the development of cardiac hypertrophy and fibrosis in CKD. AST-120 may suppress oxidative stress and reduce cardiac damage in CKD.
authors.affiliation: Division of Nephrology and Kidney Center, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Nishijima
authors.forename: Sumie
authors.initials: S
authors.lastname: Goto
authors.forename: Mikio
authors.initials: M
authors.lastname: Sugano
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamato
authors.forename: Riko
authors.initials: R
authors.lastname: Kitazawa
authors.forename: Sohei
authors.initials: S
authors.lastname: Kitazawa
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
mesh_terms: D000818:Animals; D002244:Carbon / Q000008:administration & dosage*; D002908:Chronic Disease; D018450:Disease Progression; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010087:Oxides / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D010087:Oxides; D002244:Carbon; C040896:AST 120