Administration of oral charcoal adsorbent (AST-120) suppresses low-turnover bone progression in uraemic rats.
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 microm(3)/m(2)/year in controls given vehicle and was 11.7 +/- 2.4 microm(3)/m(2)/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.


CONCLUSIONS
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.
Iwasaki
Yoshiko
Y
Department of Health Sciences, Oiya University of Nursing and Health Sciences, Oita 870-1201, Japan.
Yamato
Hideyuki
H
Nii-Kono
Tomoko
T
Fujieda
Ayako
A
Uchida
Motoyuki
M
Hosokawa
Atsuko
A
Motojima
Masaru
M
Fukagawa
Masafumi
M
D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000652:urine; D002244:Carbon / Q000008:administration & dosage / Q000494:pharmacology*; D002606:Charcoal / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003401:Creatine / Q000097:blood / Q000652:urine; D015870:Gene Expression / Q000187:drug effects; D007200:Indican / Q000097:blood; D008297:Male; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000378:metabolism; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D014511:Uremia / Q000139:chemically induced / Q000378:metabolism*
D029362:Organic Anion Transporters, Sodium-Independent; D010087:Oxides; D010281:Parathyroid Hormone; C114338:organic anion transport protein 3; D002606:Charcoal; D010758:Phosphorus; D002244:Carbon; C040896:AST 120; D000469:Alkaline Phosphatase; D003401:Creatine; D007200:Indican; D002118:Calcium