NDT Advance Access published online on July 4, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl311
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita 870-1201, Japan
* To whom correspondence should be addressed. 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.
Received December 26, 2005
Accepted May 3, 2006
Original Article
Administration of oral charcoal adsorbent (AST-120) suppresses low-turnover bone progression in uraemic rats
Yoshiko Iwasaki 1,
Hideyuki Yamato 2,
Tomoko Nii-Kono 3,
Ayako Fujieda 4,
Motoyuki Uchida 4,
Atsuko Hosokawa 4,
Masaru Motojima 5,
and
Masafumi Fukagawa 3 *
2 Division of Development, Kureha Special Laboratory, Fukushima 974-8232, Japan
3 Division of Nephrology and Dialysis Center, Kobe University School of Medicine, Kobe 650-0017, Japan
4 Biomedical Research Laboratories, Kureha Corporation, Tokyo 169-8503, Japan
5 Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Masafumi Fukagawa, E-mail: fukagawa{at}med.kobe-u.ac.jp
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Segawa, A. Onitsuka, J. Furutani, I. Kaneko, F. Aranami, N. Matsumoto, Y. Tomoe, M. Kuwahata, M. Ito, M. Matsumoto, et al. Npt2a and Npt2c in mice play distinct and synergistic roles in inorganic phosphate metabolism and skeletal development Am J Physiol Renal Physiol, September 1, 2009; 297(3): F671 - F678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Segawa, A. Onitsuka, M. Kuwahata, E. Hanabusa, J. Furutani, I. Kaneko, Y. Tomoe, F. Aranami, N. Matsumoto, M. Ito, et al. Type IIc Sodium-Dependent Phosphate Transporter Regulates Calcium Metabolism J. Am. Soc. Nephrol., January 1, 2009; 20(1): 104 - 113. [Abstract] [Full Text] [PDF]
|
|