The chemistry of thiosulfate and vascular calcification
Thiosulfate has been shown to inhibit vascular calcification in uremic rats and may inhibit calcification in humans with end-stage renal disease but whether this is due to a systemic or local action is unknown. The underlying mechanism is also unclear but complexation of calcium ions has been propos...
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description | Thiosulfate has been shown to inhibit vascular calcification in uremic rats and may inhibit calcification in humans with end-stage renal disease but whether this is due to a systemic or local action is unknown. The underlying mechanism is also unclear but complexation of calcium ions has been proposed.
In vitro assays were used to determine the effect of thiosulfate on vascular calcification and hydroxyapatite formation.
Thiosulfate (EC50: 1-2 mM) prevented calcification of injured or devitalized aortas but not uninjured aortas, and similar results were obtained with sulfate. There was no effect on reversal of calcification. Measurements with an ion-sensitive electrode (corrected for changes in ionic strength) revealed a very weak interaction between thiosulfate and Ca(2+) (K(a) = 10.9 ± 1.0 × 10(-6) M(-1)) that resulted in a 4% decrease in ionized Ca(2+) in culture medium at 5 mM thiosulfate and a corresponding 5% increase in the solubility product for calcium-phosphate. Adjustment of the total Ca(2+) concentration to account for this did not prevent the inhibition of aortic calcification by thiosulfate. Thiosulfate did not inhibit hydroxyapatite formation from seed crystals or the calcification of purified elastin and did not alter medium pH.
Thiosulfate inhibits vascular calcification at millimolar concentrations through a direct extracellular effect that does not require intact smooth muscle cells but is related to cellular injury. This effect is not specific for thiosulfate since sulfate has similar properties. Inhibition cannot be explained by effects on ionized calcium, calcium-phosphate solubility, pH, oxidative stress or hydroxyapatite formation. |
doi_str_mv | 10.1093/ndt/gfr375 |
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In vitro assays were used to determine the effect of thiosulfate on vascular calcification and hydroxyapatite formation.
Thiosulfate (EC50: 1-2 mM) prevented calcification of injured or devitalized aortas but not uninjured aortas, and similar results were obtained with sulfate. There was no effect on reversal of calcification. Measurements with an ion-sensitive electrode (corrected for changes in ionic strength) revealed a very weak interaction between thiosulfate and Ca(2+) (K(a) = 10.9 ± 1.0 × 10(-6) M(-1)) that resulted in a 4% decrease in ionized Ca(2+) in culture medium at 5 mM thiosulfate and a corresponding 5% increase in the solubility product for calcium-phosphate. Adjustment of the total Ca(2+) concentration to account for this did not prevent the inhibition of aortic calcification by thiosulfate. Thiosulfate did not inhibit hydroxyapatite formation from seed crystals or the calcification of purified elastin and did not alter medium pH.
Thiosulfate inhibits vascular calcification at millimolar concentrations through a direct extracellular effect that does not require intact smooth muscle cells but is related to cellular injury. This effect is not specific for thiosulfate since sulfate has similar properties. Inhibition cannot be explained by effects on ionized calcium, calcium-phosphate solubility, pH, oxidative stress or hydroxyapatite formation.</description><identifier>ISSN: 0931-0509</identifier><identifier>EISSN: 1460-2385</identifier><identifier>DOI: 10.1093/ndt/gfr375</identifier><identifier>PMID: 21737516</identifier><identifier>CODEN: NDTREA</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Aorta ; Aorta - drug effects ; Aorta - metabolism ; Aorta - pathology ; Biological and medical sciences ; Calcification ; Calcification (ectopic) ; Calcium ; Cell culture ; Crystals ; Culture Media, Conditioned ; Dose-Response Relationship, Drug ; Durapatite - metabolism ; Elastin ; Electrodes ; Emergency and intensive care: renal failure. Dialysis management ; End-stage renal disease ; Hydroxyapatite ; Injuries ; Intensive care medicine ; Ionic strength ; Ions ; Male ; Medical sciences ; Models, Animal ; Original ; Oxidative stress ; pH effects ; Phosphates - pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Seeds ; Sensitivity and Specificity ; Solubility ; Sulfate ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; thiosulfate ; Thiosulfates - metabolism ; Thiosulfates - pharmacology ; Tissue Culture Techniques ; Vascular Calcification - prevention & control ; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels ; Vascular System Injuries - drug therapy ; Vascular System Injuries - pathology</subject><ispartof>Nephrology, dialysis, transplantation, 2012-02, Vol.27 (2), p.521-526</ispartof><rights>2015 INIST-CNRS</rights><rights>The Author 2011. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-62ea0802258683444d1cb2156a0d768382c00ff6b51478ebbb54181af491ff103</citedby><cites>FETCH-LOGICAL-c440t-62ea0802258683444d1cb2156a0d768382c00ff6b51478ebbb54181af491ff103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25761905$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21737516$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>O'NEILL, W. Charles</creatorcontrib><creatorcontrib>HARDCASTLE, Kenneth I</creatorcontrib><title>The chemistry of thiosulfate and vascular calcification</title><title>Nephrology, dialysis, transplantation</title><addtitle>Nephrol Dial Transplant</addtitle><description>Thiosulfate has been shown to inhibit vascular calcification in uremic rats and may inhibit calcification in humans with end-stage renal disease but whether this is due to a systemic or local action is unknown. The underlying mechanism is also unclear but complexation of calcium ions has been proposed.
In vitro assays were used to determine the effect of thiosulfate on vascular calcification and hydroxyapatite formation.
Thiosulfate (EC50: 1-2 mM) prevented calcification of injured or devitalized aortas but not uninjured aortas, and similar results were obtained with sulfate. There was no effect on reversal of calcification. Measurements with an ion-sensitive electrode (corrected for changes in ionic strength) revealed a very weak interaction between thiosulfate and Ca(2+) (K(a) = 10.9 ± 1.0 × 10(-6) M(-1)) that resulted in a 4% decrease in ionized Ca(2+) in culture medium at 5 mM thiosulfate and a corresponding 5% increase in the solubility product for calcium-phosphate. Adjustment of the total Ca(2+) concentration to account for this did not prevent the inhibition of aortic calcification by thiosulfate. Thiosulfate did not inhibit hydroxyapatite formation from seed crystals or the calcification of purified elastin and did not alter medium pH.
Thiosulfate inhibits vascular calcification at millimolar concentrations through a direct extracellular effect that does not require intact smooth muscle cells but is related to cellular injury. This effect is not specific for thiosulfate since sulfate has similar properties. Inhibition cannot be explained by effects on ionized calcium, calcium-phosphate solubility, pH, oxidative stress or hydroxyapatite formation.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Aorta</subject><subject>Aorta - drug effects</subject><subject>Aorta - metabolism</subject><subject>Aorta - pathology</subject><subject>Biological and medical sciences</subject><subject>Calcification</subject><subject>Calcification (ectopic)</subject><subject>Calcium</subject><subject>Cell culture</subject><subject>Crystals</subject><subject>Culture Media, Conditioned</subject><subject>Dose-Response Relationship, Drug</subject><subject>Durapatite - metabolism</subject><subject>Elastin</subject><subject>Electrodes</subject><subject>Emergency and intensive care: renal failure. Dialysis management</subject><subject>End-stage renal disease</subject><subject>Hydroxyapatite</subject><subject>Injuries</subject><subject>Intensive care medicine</subject><subject>Ionic strength</subject><subject>Ions</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Animal</subject><subject>Original</subject><subject>Oxidative stress</subject><subject>pH effects</subject><subject>Phosphates - pharmacology</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Seeds</subject><subject>Sensitivity and Specificity</subject><subject>Solubility</subject><subject>Sulfate</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>thiosulfate</subject><subject>Thiosulfates - metabolism</subject><subject>Thiosulfates - pharmacology</subject><subject>Tissue Culture Techniques</subject><subject>Vascular Calcification - prevention & control</subject><subject>Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels</subject><subject>Vascular System Injuries - drug therapy</subject><subject>Vascular System Injuries - pathology</subject><issn>0931-0509</issn><issn>1460-2385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1LxDAQhoMouq5e_AHSiyBC3Zk0adqLIOIXLHhZzyFNEzfSbTRphf33Rnb9Og3MPLwz8xBygnCJUBezvh1mLzYUgu-QCbISclpUfJdM0hBz4FAfkMMYXwGgpkLskwOKItFYTohYLE2ml2bl4hDWmbfZsHQ-jp1Vg8lU32YfKuqxUyHTqtPOOq0G5_sjsmdVF83xtk7J893t4uYhnz_dP95cz3PNGAx5SY2CCijlVVkVjLEWdUORlwpakToV1QDWlg1HJirTNA1nWKGyrEZrEYopudrkvo3NyrTa9ENQnXwLbqXCWnrl5P9J75byxX_IggouKp4CzrcBwb-PJg4yvapN16ne-DFKBJruw7ouEnqxQXXwMQZjf9YgyC_TMpmWG9MJPv172A_6rTYBZ1sgCVSdDarXLv5yXJRYAy8-ATWahz8</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>O'NEILL, W. Charles</creator><creator>HARDCASTLE, Kenneth I</creator><general>Oxford University Press</general><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>5PM</scope></search><sort><creationdate>20120201</creationdate><title>The chemistry of thiosulfate and vascular calcification</title><author>O'NEILL, W. Charles ; HARDCASTLE, Kenneth I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-62ea0802258683444d1cb2156a0d768382c00ff6b51478ebbb54181af491ff103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Aorta</topic><topic>Aorta - drug effects</topic><topic>Aorta - metabolism</topic><topic>Aorta - pathology</topic><topic>Biological and medical sciences</topic><topic>Calcification</topic><topic>Calcification (ectopic)</topic><topic>Calcium</topic><topic>Cell culture</topic><topic>Crystals</topic><topic>Culture Media, Conditioned</topic><topic>Dose-Response Relationship, Drug</topic><topic>Durapatite - metabolism</topic><topic>Elastin</topic><topic>Electrodes</topic><topic>Emergency and intensive care: renal failure. Dialysis management</topic><topic>End-stage renal disease</topic><topic>Hydroxyapatite</topic><topic>Injuries</topic><topic>Intensive care medicine</topic><topic>Ionic strength</topic><topic>Ions</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Models, Animal</topic><topic>Original</topic><topic>Oxidative stress</topic><topic>pH effects</topic><topic>Phosphates - pharmacology</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Seeds</topic><topic>Sensitivity and Specificity</topic><topic>Solubility</topic><topic>Sulfate</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>thiosulfate</topic><topic>Thiosulfates - metabolism</topic><topic>Thiosulfates - pharmacology</topic><topic>Tissue Culture Techniques</topic><topic>Vascular Calcification - prevention & control</topic><topic>Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels</topic><topic>Vascular System Injuries - drug therapy</topic><topic>Vascular System Injuries - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>O'NEILL, W. Charles</creatorcontrib><creatorcontrib>HARDCASTLE, Kenneth I</creatorcontrib><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>PubMed Central (Full Participant titles)</collection><jtitle>Nephrology, dialysis, transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>O'NEILL, W. Charles</au><au>HARDCASTLE, Kenneth I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The chemistry of thiosulfate and vascular calcification</atitle><jtitle>Nephrology, dialysis, transplantation</jtitle><addtitle>Nephrol Dial Transplant</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>27</volume><issue>2</issue><spage>521</spage><epage>526</epage><pages>521-526</pages><issn>0931-0509</issn><eissn>1460-2385</eissn><coden>NDTREA</coden><abstract>Thiosulfate has been shown to inhibit vascular calcification in uremic rats and may inhibit calcification in humans with end-stage renal disease but whether this is due to a systemic or local action is unknown. The underlying mechanism is also unclear but complexation of calcium ions has been proposed.
In vitro assays were used to determine the effect of thiosulfate on vascular calcification and hydroxyapatite formation.
Thiosulfate (EC50: 1-2 mM) prevented calcification of injured or devitalized aortas but not uninjured aortas, and similar results were obtained with sulfate. There was no effect on reversal of calcification. Measurements with an ion-sensitive electrode (corrected for changes in ionic strength) revealed a very weak interaction between thiosulfate and Ca(2+) (K(a) = 10.9 ± 1.0 × 10(-6) M(-1)) that resulted in a 4% decrease in ionized Ca(2+) in culture medium at 5 mM thiosulfate and a corresponding 5% increase in the solubility product for calcium-phosphate. Adjustment of the total Ca(2+) concentration to account for this did not prevent the inhibition of aortic calcification by thiosulfate. Thiosulfate did not inhibit hydroxyapatite formation from seed crystals or the calcification of purified elastin and did not alter medium pH.
Thiosulfate inhibits vascular calcification at millimolar concentrations through a direct extracellular effect that does not require intact smooth muscle cells but is related to cellular injury. This effect is not specific for thiosulfate since sulfate has similar properties. Inhibition cannot be explained by effects on ionized calcium, calcium-phosphate solubility, pH, oxidative stress or hydroxyapatite formation.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>21737516</pmid><doi>10.1093/ndt/gfr375</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Aorta Aorta - drug effects Aorta - metabolism Aorta - pathology Biological and medical sciences Calcification Calcification (ectopic) Calcium Cell culture Crystals Culture Media, Conditioned Dose-Response Relationship, Drug Durapatite - metabolism Elastin Electrodes Emergency and intensive care: renal failure. Dialysis management End-stage renal disease Hydroxyapatite Injuries Intensive care medicine Ionic strength Ions Male Medical sciences Models, Animal Original Oxidative stress pH effects Phosphates - pharmacology Random Allocation Rats Rats, Sprague-Dawley Seeds Sensitivity and Specificity Solubility Sulfate Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases thiosulfate Thiosulfates - metabolism Thiosulfates - pharmacology Tissue Culture Techniques Vascular Calcification - prevention & control Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels Vascular System Injuries - drug therapy Vascular System Injuries - pathology |
title | The chemistry of thiosulfate and vascular calcification |
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