Influence of molecular weight of chemically sulfated citrus pectin fractions on their antithrombotic and bleeding effects.
Identifieur interne : 000915 ( PubMed/Checkpoint ); précédent : 000914; suivant : 000916Influence of molecular weight of chemically sulfated citrus pectin fractions on their antithrombotic and bleeding effects.
Auteurs : Thales R. Cipriani [Brésil] ; Ana Helena P. Gracher ; Lauro M. De Souza ; Roberto J C. Fonseca ; Celso L R. Belmiro ; Philip A J. Gorin ; Guilherme L. Sassaki ; Marcello IacominiSource :
- Thrombosis and haemostasis [ 0340-6245 ] ; 2009.
English descriptors
- KwdEn :
- Animals, Anticoagulants (chemistry), Anticoagulants (isolation & purification), Anticoagulants (pharmacology), Anticoagulants (toxicity), Blood Coagulation (drug effects), Citrus sinensis (chemistry), Disease Models, Animal, Dose-Response Relationship, Drug, Factor Xa Inhibitors, Female, Fibrinolytic Agents (chemistry), Fibrinolytic Agents (isolation & purification), Fibrinolytic Agents (pharmacology), Fibrinolytic Agents (toxicity), Hemorrhage (chemically induced), Humans, Male, Molecular Weight, Pectins (chemistry), Pectins (isolation & purification), Pectins (pharmacology), Pectins (toxicity), Platelet Aggregation (drug effects), Rats, Rats, Wistar, Structure-Activity Relationship, Sulfates (chemistry), Sulfates (isolation & purification), Sulfates (pharmacology), Sulfates (toxicity), Thrombin (antagonists & inhibitors), Venous Thrombosis (blood), Venous Thrombosis (prevention & control).
- MESH :
- chemical , antagonists & inhibitors : Thrombin.
- chemical , chemistry : Anticoagulants, Fibrinolytic Agents, Pectins, Sulfates.
- chemical , isolation & purification : Anticoagulants, Fibrinolytic Agents, Pectins, Sulfates.
- chemical , pharmacology : Anticoagulants, Fibrinolytic Agents, Pectins, Sulfates.
- chemical , toxicity : Anticoagulants, Fibrinolytic Agents, Pectins, Sulfates.
- blood : Venous Thrombosis.
- chemically induced : Hemorrhage.
- chemistry : Citrus sinensis.
- drug effects : Blood Coagulation, Platelet Aggregation.
- prevention & control : Venous Thrombosis.
- Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Factor Xa Inhibitors, Female, Humans, Male, Molecular Weight, Rats, Rats, Wistar, Structure-Activity Relationship.
Abstract
Evaluated were the anticoagulant and antithrombotic activities, and bleeding effect of two chemically sulfated polysaccharides, obtained from citric pectin, with different average molar masses. Both low-molecular-weight (Pec-LWS, 3,600 g/mol) and high-molecular-weight sulfated pectins (Pec-HWS, 12,000 g/mol) had essentially the same structure, consisting of a (1-->4)-linked alpha-D-GalpA chain with almost all its HO-2 and HO-3 groups substituted by sulfate. Both polysaccharides had anticoagulant activity in vitro, although Pec-HWS was a more potent antithrombotic agent in vivo, giving rise to total inhibition of venous thrombosis at a dose of 3.5 mg/kg body weight. Surprisingly, in contrast with heparin, Pec-HWS and Pec-LWS are able to directly inhibit alpha-thrombin and factor Xa by a mechanism independent of antithrombin (AT) and/or heparin co-factor II (HCII). Moreover, Pec-HWS provided a lower risk of bleeding than heparin at a dose of 100% effectiveness against venous thrombosis, indicating it to be a promising antithrombotic agent.
PubMed: 19404539
Affiliations:
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Cipriani</name><affiliation wicri:level="2"><nlm:affiliation>Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, CP 19046, CEP 81.531-980, Curitiba, PR, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, CP 19046, CEP 81.531-980, Curitiba, PR</wicri:regionArea><placeName><region type="state">Paraná (État)</region></placeName></affiliation></author><author><name sortKey="Gracher, Ana Helena P" sort="Gracher, Ana Helena P" uniqKey="Gracher A" first="Ana Helena P" last="Gracher">Ana Helena P. Gracher</name></author><author><name sortKey="De Souza, Lauro M" sort="De Souza, Lauro M" uniqKey="De Souza L" first="Lauro M" last="De Souza">Lauro M. De Souza</name></author><author><name sortKey="Fonseca, Roberto J C" sort="Fonseca, Roberto J C" uniqKey="Fonseca R" first="Roberto J C" last="Fonseca">Roberto J C. Fonseca</name></author><author><name sortKey="Belmiro, Celso L R" sort="Belmiro, Celso L R" uniqKey="Belmiro C" first="Celso L R" last="Belmiro">Celso L R. Belmiro</name></author><author><name sortKey="Gorin, Philip A J" sort="Gorin, Philip A J" uniqKey="Gorin P" first="Philip A J" last="Gorin">Philip A J. Gorin</name></author><author><name sortKey="Sassaki, Guilherme L" sort="Sassaki, Guilherme L" uniqKey="Sassaki G" first="Guilherme L" last="Sassaki">Guilherme L. Sassaki</name></author><author><name sortKey="Iacomini, Marcello" sort="Iacomini, Marcello" uniqKey="Iacomini M" first="Marcello" last="Iacomini">Marcello Iacomini</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2009">2009</date><idno type="RBID">pubmed:19404539</idno><idno type="pmid">19404539</idno><idno type="wicri:Area/PubMed/Corpus">000960</idno><idno type="wicri:Area/PubMed/Curation">000960</idno><idno type="wicri:Area/PubMed/Checkpoint">000960</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Influence of molecular weight of chemically sulfated citrus pectin fractions on their antithrombotic and bleeding effects.</title><author><name sortKey="Cipriani, Thales R" sort="Cipriani, Thales R" uniqKey="Cipriani T" first="Thales R" last="Cipriani">Thales R. Cipriani</name><affiliation wicri:level="2"><nlm:affiliation>Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, CP 19046, CEP 81.531-980, Curitiba, PR, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, CP 19046, CEP 81.531-980, Curitiba, PR</wicri:regionArea><placeName><region type="state">Paraná (État)</region></placeName></affiliation></author><author><name sortKey="Gracher, Ana Helena P" sort="Gracher, Ana Helena P" uniqKey="Gracher A" first="Ana Helena P" last="Gracher">Ana Helena P. Gracher</name></author><author><name sortKey="De Souza, Lauro M" sort="De Souza, Lauro M" uniqKey="De Souza L" first="Lauro M" last="De Souza">Lauro M. De Souza</name></author><author><name sortKey="Fonseca, Roberto J C" sort="Fonseca, Roberto J C" uniqKey="Fonseca R" first="Roberto J C" last="Fonseca">Roberto J C. Fonseca</name></author><author><name sortKey="Belmiro, Celso L R" sort="Belmiro, Celso L R" uniqKey="Belmiro C" first="Celso L R" last="Belmiro">Celso L R. Belmiro</name></author><author><name sortKey="Gorin, Philip A J" sort="Gorin, Philip A J" uniqKey="Gorin P" first="Philip A J" last="Gorin">Philip A J. Gorin</name></author><author><name sortKey="Sassaki, Guilherme L" sort="Sassaki, Guilherme L" uniqKey="Sassaki G" first="Guilherme L" last="Sassaki">Guilherme L. Sassaki</name></author><author><name sortKey="Iacomini, Marcello" sort="Iacomini, Marcello" uniqKey="Iacomini M" first="Marcello" last="Iacomini">Marcello Iacomini</name></author></analytic><series><title level="j">Thrombosis and haemostasis</title><idno type="ISSN">0340-6245</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Anticoagulants (chemistry)</term><term>Anticoagulants (isolation & purification)</term><term>Anticoagulants (pharmacology)</term><term>Anticoagulants (toxicity)</term><term>Blood Coagulation (drug effects)</term><term>Citrus sinensis (chemistry)</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Factor Xa Inhibitors</term><term>Female</term><term>Fibrinolytic Agents (chemistry)</term><term>Fibrinolytic Agents (isolation & purification)</term><term>Fibrinolytic Agents (pharmacology)</term><term>Fibrinolytic Agents (toxicity)</term><term>Hemorrhage (chemically induced)</term><term>Humans</term><term>Male</term><term>Molecular Weight</term><term>Pectins (chemistry)</term><term>Pectins (isolation & purification)</term><term>Pectins (pharmacology)</term><term>Pectins (toxicity)</term><term>Platelet Aggregation (drug effects)</term><term>Rats</term><term>Rats, Wistar</term><term>Structure-Activity Relationship</term><term>Sulfates (chemistry)</term><term>Sulfates (isolation & purification)</term><term>Sulfates (pharmacology)</term><term>Sulfates (toxicity)</term><term>Thrombin (antagonists & inhibitors)</term><term>Venous Thrombosis (blood)</term><term>Venous Thrombosis (prevention & control)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Thrombin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Anticoagulants</term><term>Fibrinolytic Agents</term><term>Pectins</term><term>Sulfates</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Anticoagulants</term><term>Fibrinolytic Agents</term><term>Pectins</term><term>Sulfates</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anticoagulants</term><term>Fibrinolytic Agents</term><term>Pectins</term><term>Sulfates</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Anticoagulants</term><term>Fibrinolytic Agents</term><term>Pectins</term><term>Sulfates</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Venous Thrombosis</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Hemorrhage</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Citrus sinensis</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Blood Coagulation</term><term>Platelet Aggregation</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Venous Thrombosis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Factor Xa Inhibitors</term><term>Female</term><term>Humans</term><term>Male</term><term>Molecular Weight</term><term>Rats</term><term>Rats, Wistar</term><term>Structure-Activity Relationship</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Evaluated were the anticoagulant and antithrombotic activities, and bleeding effect of two chemically sulfated polysaccharides, obtained from citric pectin, with different average molar masses. Both low-molecular-weight (Pec-LWS, 3,600 g/mol) and high-molecular-weight sulfated pectins (Pec-HWS, 12,000 g/mol) had essentially the same structure, consisting of a (1-->4)-linked alpha-D-GalpA chain with almost all its HO-2 and HO-3 groups substituted by sulfate. Both polysaccharides had anticoagulant activity in vitro, although Pec-HWS was a more potent antithrombotic agent in vivo, giving rise to total inhibition of venous thrombosis at a dose of 3.5 mg/kg body weight. Surprisingly, in contrast with heparin, Pec-HWS and Pec-LWS are able to directly inhibit alpha-thrombin and factor Xa by a mechanism independent of antithrombin (AT) and/or heparin co-factor II (HCII). Moreover, Pec-HWS provided a lower risk of bleeding than heparin at a dose of 100% effectiveness against venous thrombosis, indicating it to be a promising antithrombotic agent.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">19404539</PMID><DateCreated><Year>2009</Year><Month>4</Month><Day>30</Day></DateCreated><DateCompleted><Year>2009</Year><Month>06</Month><Day>19</Day></DateCompleted><DateRevised><Year>2014</Year><Month>11</Month><Day>20</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0340-6245</ISSN><JournalIssue CitedMedium="Print"><Volume>101</Volume><Issue>5</Issue><PubDate><Year>2009</Year><Month>May</Month></PubDate></JournalIssue><Title>Thrombosis and haemostasis</Title><ISOAbbreviation>Thromb. Haemost.</ISOAbbreviation></Journal><ArticleTitle>Influence of molecular weight of chemically sulfated citrus pectin fractions on their antithrombotic and bleeding effects.</ArticleTitle><Pagination><MedlinePgn>860-6</MedlinePgn></Pagination><Abstract><AbstractText>Evaluated were the anticoagulant and antithrombotic activities, and bleeding effect of two chemically sulfated polysaccharides, obtained from citric pectin, with different average molar masses. Both low-molecular-weight (Pec-LWS, 3,600 g/mol) and high-molecular-weight sulfated pectins (Pec-HWS, 12,000 g/mol) had essentially the same structure, consisting of a (1-->4)-linked alpha-D-GalpA chain with almost all its HO-2 and HO-3 groups substituted by sulfate. Both polysaccharides had anticoagulant activity in vitro, although Pec-HWS was a more potent antithrombotic agent in vivo, giving rise to total inhibition of venous thrombosis at a dose of 3.5 mg/kg body weight. Surprisingly, in contrast with heparin, Pec-HWS and Pec-LWS are able to directly inhibit alpha-thrombin and factor Xa by a mechanism independent of antithrombin (AT) and/or heparin co-factor II (HCII). Moreover, Pec-HWS provided a lower risk of bleeding than heparin at a dose of 100% effectiveness against venous thrombosis, indicating it to be a promising antithrombotic agent.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cipriani</LastName><ForeName>Thales R</ForeName><Initials>TR</Initials><AffiliationInfo><Affiliation>Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, CP 19046, CEP 81.531-980, Curitiba, PR, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gracher</LastName><ForeName>Ana Helena P</ForeName><Initials>AH</Initials></Author><Author ValidYN="Y"><LastName>de Souza</LastName><ForeName>Lauro M</ForeName><Initials>LM</Initials></Author><Author ValidYN="Y"><LastName>Fonseca</LastName><ForeName>Roberto J C</ForeName><Initials>RJ</Initials></Author><Author ValidYN="Y"><LastName>Belmiro</LastName><ForeName>Celso L R</ForeName><Initials>CL</Initials></Author><Author ValidYN="Y"><LastName>Gorin</LastName><ForeName>Philip A J</ForeName><Initials>PA</Initials></Author><Author ValidYN="Y"><LastName>Sassaki</LastName><ForeName>Guilherme L</ForeName><Initials>GL</Initials></Author><Author ValidYN="Y"><LastName>Iacomini</LastName><ForeName>Marcello</ForeName><Initials>M</Initials></Author></AuthorList><Language>ENG</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Thromb Haemost</MedlineTA><NlmUniqueID>7608063</NlmUniqueID><ISSNLinking>0340-6245</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000925">Anticoagulants</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D065427">Factor Xa Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005343">Fibrinolytic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010368">Pectins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013431">Sulfates</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.21.5</RegistryNumber><NameOfSubstance UI="D013917">Thrombin</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000925" MajorTopicYN="N">Anticoagulants</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000633" MajorTopicYN="N">toxicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001777" MajorTopicYN="N">Blood Coagulation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D032084" MajorTopicYN="Y">Citrus sinensis</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065427" MajorTopicYN="N">Factor Xa Inhibitors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005343" MajorTopicYN="N">Fibrinolytic Agents</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000633" MajorTopicYN="N">toxicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006470" MajorTopicYN="N">Hemorrhage</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008970" MajorTopicYN="N">Molecular Weight</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010368" MajorTopicYN="N">Pectins</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000633" MajorTopicYN="N">toxicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010974" MajorTopicYN="N">Platelet Aggregation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017208" MajorTopicYN="N">Rats, Wistar</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013431" MajorTopicYN="N">Sulfates</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName><QualifierName UI="Q000494" 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PubStatus="medline"><Year>2009</Year><Month>6</Month><Day>20</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">19404539</ArticleId><ArticleId IdType="pii">09050860</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Brésil</li></country><region><li>Paraná (État)</li></region></list><tree><noCountry><name sortKey="Belmiro, Celso L R" sort="Belmiro, Celso L R" uniqKey="Belmiro C" first="Celso L R" last="Belmiro">Celso L R. Belmiro</name><name sortKey="De Souza, Lauro M" sort="De Souza, Lauro M" uniqKey="De Souza L" first="Lauro M" last="De Souza">Lauro M. De Souza</name><name sortKey="Fonseca, Roberto J C" sort="Fonseca, Roberto J C" uniqKey="Fonseca R" first="Roberto J C" last="Fonseca">Roberto J C. Fonseca</name><name sortKey="Gorin, Philip A J" sort="Gorin, Philip A J" uniqKey="Gorin P" first="Philip A J" last="Gorin">Philip A J. Gorin</name><name sortKey="Gracher, Ana Helena P" sort="Gracher, Ana Helena P" uniqKey="Gracher A" first="Ana Helena P" last="Gracher">Ana Helena P. Gracher</name><name sortKey="Iacomini, Marcello" sort="Iacomini, Marcello" uniqKey="Iacomini M" first="Marcello" last="Iacomini">Marcello Iacomini</name><name sortKey="Sassaki, Guilherme L" sort="Sassaki, Guilherme L" uniqKey="Sassaki G" first="Guilherme L" last="Sassaki">Guilherme L. Sassaki</name></noCountry><country name="Brésil"><region name="Paraná (État)"><name sortKey="Cipriani, Thales R" sort="Cipriani, Thales R" uniqKey="Cipriani T" first="Thales R" last="Cipriani">Thales R. Cipriani</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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