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 develo...
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| creator | Iwasaki, Yoshiko Yamato, Hideyuki Nii-Kono, Tomoko Fujieda, Ayako Uchida, Motoyuki Hosokawa, Atsuko Motojima, Masaru Fukagawa, Masafumi |
| description | 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. |
| doi_str_mv | 10.1093/ndt/gfl311 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_19328014</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1132299881</sourcerecordid><originalsourceid>FETCH-LOGICAL-c477t-256022c958c695d31dfd5b27618b21f0388c1864d9e1b9e7e9f99e84554229b3</originalsourceid><addsrcrecordid>eNpd0V1rFDEUBuBQlHat3vQHlFBQVBibk0y-LpdWXWFB0L2Q3oRMJtNOO5Nskxk__r1ZdrHgVQLn4eXkDUJnQD4A0ewytNPlbTcwgCO0gFqQijLFn6FFGUJFONEn6EXO94QQTaU8RicgFCVMigUalu3Yhz5PyU59DDh2OCY7YHdnk4vlYtscU-PDhN8uv28qoOQdzvN2m3zOPuMh_qqmOYX40yfcxODxNsXb3XCX1gc8J-vH3uGSn1-i550dsn91OE_R5tPHzdWqWn_9_OVqua5cLeVUUS4IpU5z5YTmLYO2a3lDpQDVUOgIU8qBEnWrPTTaS687rb2qOa8p1Q07RW_2sWWVx9nnyYx9dn4YbPBxzgY0o4pAXeDFf_A-lreU1QwFBVxrKgp6v0cuxZyT78w29aNNfwwQs-vflP7Nvv-Czw-JczP69okeCi_g9QHY7OzQJRtcn5-copQDZcVVe1e-xv_-N7fpwQjJJDerHzfmeqWuv-nN2qzZXyTZnQA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>218159926</pqid></control><display><type>article</type><title>Administration of oral charcoal adsorbent (AST-120) suppresses low-turnover bone progression in uraemic rats</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Iwasaki, Yoshiko ; Yamato, Hideyuki ; Nii-Kono, Tomoko ; Fujieda, Ayako ; Uchida, Motoyuki ; Hosokawa, Atsuko ; Motojima, Masaru ; Fukagawa, Masafumi</creator><creatorcontrib>Iwasaki, Yoshiko ; Yamato, Hideyuki ; Nii-Kono, Tomoko ; Fujieda, Ayako ; Uchida, Motoyuki ; Hosokawa, Atsuko ; Motojima, Masaru ; Fukagawa, Masafumi</creatorcontrib><description>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.</description><identifier>ISSN: 0931-0509</identifier><identifier>EISSN: 1460-2385</identifier><identifier>DOI: 10.1093/ndt/gfl311</identifier><identifier>PMID: 16820376</identifier><identifier>CODEN: NDTREA</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Administration, Oral ; Alkaline Phosphatase - blood ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Biological and medical sciences ; Bone and Bones - drug effects ; Bone and Bones - metabolism ; Calcium - blood ; Calcium - urine ; Carbon - administration & dosage ; Carbon - pharmacology ; Charcoal - administration & dosage ; Charcoal - pharmacology ; Chromatography, High Pressure Liquid ; Creatine - blood ; Creatine - urine ; Emergency and intensive care: renal failure. Dialysis management ; Gene Expression - drug effects ; Glomerulonephritis ; Indican - blood ; indoxyl sulphate ; Intensive care medicine ; low bone turnover ; Male ; Medical sciences ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; oral charcoal adsorbent ; Organic Anion Transporters, Sodium-Independent - genetics ; Osteoblasts - drug effects ; Osteoblasts - metabolism ; Osteogenesis - drug effects ; Oxides - administration & dosage ; Oxides - pharmacology ; Parathyroid Hormone - metabolism ; Phosphorus - blood ; Rats ; Rats, Sprague-Dawley ; Renal failure ; Reverse Transcriptase Polymerase Chain Reaction ; Tibia - drug effects ; Tibia - metabolism ; uraemic toxins ; Uremia - chemically induced ; Uremia - metabolism</subject><ispartof>Nephrology, dialysis, transplantation, 2006-10, Vol.21 (10), p.2768-2774</ispartof><rights>2006 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Oct 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-256022c958c695d31dfd5b27618b21f0388c1864d9e1b9e7e9f99e84554229b3</citedby><cites>FETCH-LOGICAL-c477t-256022c958c695d31dfd5b27618b21f0388c1864d9e1b9e7e9f99e84554229b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18225123$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16820376$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iwasaki, Yoshiko</creatorcontrib><creatorcontrib>Yamato, Hideyuki</creatorcontrib><creatorcontrib>Nii-Kono, Tomoko</creatorcontrib><creatorcontrib>Fujieda, Ayako</creatorcontrib><creatorcontrib>Uchida, Motoyuki</creatorcontrib><creatorcontrib>Hosokawa, Atsuko</creatorcontrib><creatorcontrib>Motojima, Masaru</creatorcontrib><creatorcontrib>Fukagawa, Masafumi</creatorcontrib><title>Administration of oral charcoal adsorbent (AST-120) suppresses low-turnover bone progression in uraemic rats</title><title>Nephrology, dialysis, transplantation</title><addtitle>Nephrol. Dial. Transplant</addtitle><description>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.</description><subject>Administration, Oral</subject><subject>Alkaline Phosphatase - blood</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone and Bones - drug effects</subject><subject>Bone and Bones - metabolism</subject><subject>Calcium - blood</subject><subject>Calcium - urine</subject><subject>Carbon - administration & dosage</subject><subject>Carbon - pharmacology</subject><subject>Charcoal - administration & dosage</subject><subject>Charcoal - pharmacology</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Creatine - blood</subject><subject>Creatine - urine</subject><subject>Emergency and intensive care: renal failure. Dialysis management</subject><subject>Gene Expression - drug effects</subject><subject>Glomerulonephritis</subject><subject>Indican - blood</subject><subject>indoxyl sulphate</subject><subject>Intensive care medicine</subject><subject>low bone turnover</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>oral charcoal adsorbent</subject><subject>Organic Anion Transporters, Sodium-Independent - genetics</subject><subject>Osteoblasts - drug effects</subject><subject>Osteoblasts - metabolism</subject><subject>Osteogenesis - drug effects</subject><subject>Oxides - administration & dosage</subject><subject>Oxides - pharmacology</subject><subject>Parathyroid Hormone - metabolism</subject><subject>Phosphorus - blood</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Renal failure</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Tibia - drug effects</subject><subject>Tibia - metabolism</subject><subject>uraemic toxins</subject><subject>Uremia - chemically induced</subject><subject>Uremia - metabolism</subject><issn>0931-0509</issn><issn>1460-2385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0V1rFDEUBuBQlHat3vQHlFBQVBibk0y-LpdWXWFB0L2Q3oRMJtNOO5Nskxk__r1ZdrHgVQLn4eXkDUJnQD4A0ewytNPlbTcwgCO0gFqQijLFn6FFGUJFONEn6EXO94QQTaU8RicgFCVMigUalu3Yhz5PyU59DDh2OCY7YHdnk4vlYtscU-PDhN8uv28qoOQdzvN2m3zOPuMh_qqmOYX40yfcxODxNsXb3XCX1gc8J-vH3uGSn1-i550dsn91OE_R5tPHzdWqWn_9_OVqua5cLeVUUS4IpU5z5YTmLYO2a3lDpQDVUOgIU8qBEnWrPTTaS687rb2qOa8p1Q07RW_2sWWVx9nnyYx9dn4YbPBxzgY0o4pAXeDFf_A-lreU1QwFBVxrKgp6v0cuxZyT78w29aNNfwwQs-vflP7Nvv-Czw-JczP69okeCi_g9QHY7OzQJRtcn5-copQDZcVVe1e-xv_-N7fpwQjJJDerHzfmeqWuv-nN2qzZXyTZnQA</recordid><startdate>20061001</startdate><enddate>20061001</enddate><creator>Iwasaki, Yoshiko</creator><creator>Yamato, Hideyuki</creator><creator>Nii-Kono, Tomoko</creator><creator>Fujieda, Ayako</creator><creator>Uchida, Motoyuki</creator><creator>Hosokawa, Atsuko</creator><creator>Motojima, Masaru</creator><creator>Fukagawa, Masafumi</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>20061001</creationdate><title>Administration of oral charcoal adsorbent (AST-120) suppresses low-turnover bone progression in uraemic rats</title><author>Iwasaki, Yoshiko ; Yamato, Hideyuki ; Nii-Kono, Tomoko ; Fujieda, Ayako ; Uchida, Motoyuki ; Hosokawa, Atsuko ; Motojima, Masaru ; Fukagawa, Masafumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-256022c958c695d31dfd5b27618b21f0388c1864d9e1b9e7e9f99e84554229b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Administration, Oral</topic><topic>Alkaline Phosphatase - blood</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bone and Bones - drug effects</topic><topic>Bone and Bones - metabolism</topic><topic>Calcium - blood</topic><topic>Calcium - urine</topic><topic>Carbon - administration & dosage</topic><topic>Carbon - pharmacology</topic><topic>Charcoal - administration & dosage</topic><topic>Charcoal - pharmacology</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Creatine - blood</topic><topic>Creatine - urine</topic><topic>Emergency and intensive care: renal failure. Dialysis management</topic><topic>Gene Expression - drug effects</topic><topic>Glomerulonephritis</topic><topic>Indican - blood</topic><topic>indoxyl sulphate</topic><topic>Intensive care medicine</topic><topic>low bone turnover</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>oral charcoal adsorbent</topic><topic>Organic Anion Transporters, Sodium-Independent - genetics</topic><topic>Osteoblasts - drug effects</topic><topic>Osteoblasts - metabolism</topic><topic>Osteogenesis - drug effects</topic><topic>Oxides - administration & dosage</topic><topic>Oxides - pharmacology</topic><topic>Parathyroid Hormone - metabolism</topic><topic>Phosphorus - blood</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Renal failure</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Tibia - drug effects</topic><topic>Tibia - metabolism</topic><topic>uraemic toxins</topic><topic>Uremia - chemically induced</topic><topic>Uremia - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iwasaki, Yoshiko</creatorcontrib><creatorcontrib>Yamato, Hideyuki</creatorcontrib><creatorcontrib>Nii-Kono, Tomoko</creatorcontrib><creatorcontrib>Fujieda, Ayako</creatorcontrib><creatorcontrib>Uchida, Motoyuki</creatorcontrib><creatorcontrib>Hosokawa, Atsuko</creatorcontrib><creatorcontrib>Motojima, Masaru</creatorcontrib><creatorcontrib>Fukagawa, Masafumi</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Nephrology, dialysis, transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iwasaki, Yoshiko</au><au>Yamato, Hideyuki</au><au>Nii-Kono, Tomoko</au><au>Fujieda, Ayako</au><au>Uchida, Motoyuki</au><au>Hosokawa, Atsuko</au><au>Motojima, Masaru</au><au>Fukagawa, Masafumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Administration of oral charcoal adsorbent (AST-120) suppresses low-turnover bone progression in uraemic rats</atitle><jtitle>Nephrology, dialysis, transplantation</jtitle><addtitle>Nephrol. Dial. Transplant</addtitle><date>2006-10-01</date><risdate>2006</risdate><volume>21</volume><issue>10</issue><spage>2768</spage><epage>2774</epage><pages>2768-2774</pages><issn>0931-0509</issn><eissn>1460-2385</eissn><coden>NDTREA</coden><abstract>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.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>16820376</pmid><doi>10.1093/ndt/gfl311</doi><tpages>7</tpages></addata></record> |
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| subjects | Administration, Oral Alkaline Phosphatase - blood Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Biological and medical sciences Bone and Bones - drug effects Bone and Bones - metabolism Calcium - blood Calcium - urine Carbon - administration & dosage Carbon - pharmacology Charcoal - administration & dosage Charcoal - pharmacology Chromatography, High Pressure Liquid Creatine - blood Creatine - urine Emergency and intensive care: renal failure. Dialysis management Gene Expression - drug effects Glomerulonephritis Indican - blood indoxyl sulphate Intensive care medicine low bone turnover Male Medical sciences Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure oral charcoal adsorbent Organic Anion Transporters, Sodium-Independent - genetics Osteoblasts - drug effects Osteoblasts - metabolism Osteogenesis - drug effects Oxides - administration & dosage Oxides - pharmacology Parathyroid Hormone - metabolism Phosphorus - blood Rats Rats, Sprague-Dawley Renal failure Reverse Transcriptase Polymerase Chain Reaction Tibia - drug effects Tibia - metabolism uraemic toxins Uremia - chemically induced Uremia - metabolism |
| title | Administration of oral charcoal adsorbent (AST-120) suppresses low-turnover bone progression in uraemic rats |
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