Influence of molecular weight of chemically sulfated citrus pectin fractions on their antithrombotic and bleeding effects.
Identifieur interne : 000994 ( Ncbi/Checkpoint ); précédent : 000993; suivant : 000995Influence 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. 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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. 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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><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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