NDT Advance Access originally published online on July 4, 2006
Nephrology Dialysis Transplantation 2006 21(10):2768-2774; doi:10.1093/ndt/gfl311
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Administration of oral charcoal adsorbent (AST-120) suppresses low-turnover bone progression in uraemic rats
1Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita 870-1201, 2Division of Development, Kureha Special Laboratory, Fukushima 974-8232, 3Division of Nephrology and Dialysis Center, Kobe University School of Medicine, Kobe 650-0017, 4Biomedical Research Laboratories, Kureha Corporation, Tokyo 169-8503, Japan and 5Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Correspondence and offprint requests to: Masafumi Fukagawa, MD, PhD, FJSIM, FASN, Division of Nephrology & Dialysis Center, Kobe University School of Medicine, Kobe, 650-0017, Japan. Email: fukagawa{at}med.kobe-u.ac.jp
Background. Using a rat model of renal failure with normal parathyroid hormone levels, we had demonstrated previously that bone formation decreased depending on the degree of renal dysfunction, and hypothesized that uraemic toxins (UTx) are associated with the development of low-turnover bone development, complicating renal failure. In this study, focusing on indoxyl sulphate (IS) as a representative UTx, we analysed the effect of an oral charcoal adsorbent AST-120, which removes uraemic toxins and their precursors from the gastrointestinal tract, on bone turnover.
Methods. AST-120 or vehicle was administered orally to model rats with uraemia and low turnover bone. Bone turnover was analysed by histomorphometry. Expression of osteoblast-related genes and oat-3 gene was analysed by reverse transcription polymerase chain reaction.
Results. In rats treated with vehicle, serum IS level increased with time after renal dysfunction, while bone formation decreased accompanied by down-regulation of the parathyroid/parathyroid-related peptide hormone receptor, alkaline phosphatase and osteocalcin genes. Administration of AST-120 inhibited the accumulation of IS in blood and ameliorated bone formation. Bone formation rate was 2.4 ± 1.7 µm3/m2/year in controls given vehicle and was 11.7 ± 2.4 µm3/m2/year in rats administered with AST-120 (P < 0.05). AST-120 treatment also reversed the down-regulation of osteoblast-related genes. Gene expression of oat-3 was detected in the tibia of rats.
Conclusion. Administration of the oral charcoal adsorbent AST-120 decreases the osteoblast cytotoxicity of UTx including IS, and suppresses progression of low bone turnover in uraemic rats.
Keywords: indoxyl sulphate; low bone turnover; oral charcoal adsorbent; renal failure; uraemic toxins
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