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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Veröffentlicht in:Nephrology, dialysis, transplantation dialysis, transplantation, 2012-02, Vol.27 (2), p.521-526
Hauptverfasser: O'NEILL, W. Charles, HARDCASTLE, Kenneth I
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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.
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Charles ; HARDCASTLE, Kenneth I</creator><creatorcontrib>O'NEILL, W. Charles ; HARDCASTLE, Kenneth I</creatorcontrib><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. 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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. 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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 &amp; 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 &amp; 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 &amp; 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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