Inactivation of heparin by cationically modified chitosan

2014
journal article
article
14
dc.abstract.enThis study was performed to evaluate the ability of N-(2-hydroxypropyl)-3- tri methylammonium chitosan chloride (HTCC), the cationically modified chitosan, to form biologically inactive complexes with unfractionated heparin and thereby blocking its anticoagulant activity. Experiments were carried out in rats in vivo and in vitro using the activated partial thromboplastin time (APTT) and prothrombin time (PT) tests for evaluation of heparin anticoagulant activity. For the first time we have found that HTCC effectively neutralizes anticoagulant action of heparin in rat blood in vitro as well as in rats in vivo. The effect of HTCC on suppression of heparin activity is dose-dependent and its efficacy can be comparable to that of protamine-the only agent used in clinic for heparin neutralization. HTCC administered i.v. alone had no direct effect on any of the coagulation tests used. The potential adverse effects of HTCC were further explored using rat experimental model of acute toxicity. When administered i.p. at high doses (250 and 500 mg/kg body weight), HTCC induced some significant dose-dependent structural abnormalities in the liver. However, when HTCC was administered at low doses, comparable to those used for neutralization of anticoagulant effect of heparin, no histopathological abnormalities in liver were observed.pl
dc.affiliationWydział Lekarski : Zakład Farmakologiipl
dc.affiliationWydział Chemii : Zakład Chemii Fizycznej i Elektrochemiipl
dc.affiliationWydział Lekarski : Zakład Neuropatologiipl
dc.affiliationWydział Lekarski : Zakład Patomorfologii Klinicznej i Doświadczalnejpl
dc.cm.id67836
dc.contributor.authorLorkowska-Zawicka, Barbara - 130710 pl
dc.contributor.authorKamiński, Kamil - 126126 pl
dc.contributor.authorCiejka, Justyna - 107449 pl
dc.contributor.authorSzczubiałka, Krzysztof - 132218 pl
dc.contributor.authorBiałas, Magdalena - 128741 pl
dc.contributor.authorOkoń, Krzysztof - 133027 pl
dc.contributor.authorAdamek, Dariusz - 128411 pl
dc.contributor.authorNowakowska, Maria - 131048 pl
dc.contributor.authorJawień, Jacek - 129879 pl
dc.contributor.authorOlszanecki, Rafał - 133033 pl
dc.contributor.authorKorbut, Ryszard - 130278 pl
dc.date.accession2019-02-14pl
dc.date.accessioned2015-01-15T08:34:31Z
dc.date.available2015-01-15T08:34:31Z
dc.date.issued2014pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number7pl
dc.description.physical3953-3969pl
dc.description.points40pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume12pl
dc.identifier.doi10.3390/md12073953pl
dc.identifier.eissn1660-3397pl
dc.identifier.projectROD UJ / Ppl
dc.identifier.urihttp://ruj.uj.edu.pl/xmlui/handle/item/2544
dc.identifier.weblinkhttps://www.mdpi.com/1660-3397/12/7/3953/htmpl
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 3.0 Polska*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/legalcode*
dc.share.typeotwarte czasopismo
dc.subject.enchitosanpl
dc.subject.encoagulationpl
dc.subject.enheparin antidotepl
dc.subject.enhepatotoxicitypl
dc.subject.enHTCCpl
dc.subject.enprotaminepl
dc.subject.enunfractionated heparinpl
dc.subtypeArticlepl
dc.titleInactivation of heparin by cationically modified chitosanpl
dc.title.journalMarine Drugspl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
This study was performed to evaluate the ability of N-(2-hydroxypropyl)-3- tri methylammonium chitosan chloride (HTCC), the cationically modified chitosan, to form biologically inactive complexes with unfractionated heparin and thereby blocking its anticoagulant activity. Experiments were carried out in rats in vivo and in vitro using the activated partial thromboplastin time (APTT) and prothrombin time (PT) tests for evaluation of heparin anticoagulant activity. For the first time we have found that HTCC effectively neutralizes anticoagulant action of heparin in rat blood in vitro as well as in rats in vivo. The effect of HTCC on suppression of heparin activity is dose-dependent and its efficacy can be comparable to that of protamine-the only agent used in clinic for heparin neutralization. HTCC administered i.v. alone had no direct effect on any of the coagulation tests used. The potential adverse effects of HTCC were further explored using rat experimental model of acute toxicity. When administered i.p. at high doses (250 and 500 mg/kg body weight), HTCC induced some significant dose-dependent structural abnormalities in the liver. However, when HTCC was administered at low doses, comparable to those used for neutralization of anticoagulant effect of heparin, no histopathological abnormalities in liver were observed.
dc.affiliationpl
Wydział Lekarski : Zakład Farmakologii
dc.affiliationpl
Wydział Chemii : Zakład Chemii Fizycznej i Elektrochemii
dc.affiliationpl
Wydział Lekarski : Zakład Neuropatologii
dc.affiliationpl
Wydział Lekarski : Zakład Patomorfologii Klinicznej i Doświadczalnej
dc.cm.id
67836
dc.contributor.authorpl
Lorkowska-Zawicka, Barbara - 130710
dc.contributor.authorpl
Kamiński, Kamil - 126126
dc.contributor.authorpl
Ciejka, Justyna - 107449
dc.contributor.authorpl
Szczubiałka, Krzysztof - 132218
dc.contributor.authorpl
Białas, Magdalena - 128741
dc.contributor.authorpl
Okoń, Krzysztof - 133027
dc.contributor.authorpl
Adamek, Dariusz - 128411
dc.contributor.authorpl
Nowakowska, Maria - 131048
dc.contributor.authorpl
Jawień, Jacek - 129879
dc.contributor.authorpl
Olszanecki, Rafał - 133033
dc.contributor.authorpl
Korbut, Ryszard - 130278
dc.date.accessionpl
2019-02-14
dc.date.accessioned
2015-01-15T08:34:31Z
dc.date.available
2015-01-15T08:34:31Z
dc.date.issuedpl
2014
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
7
dc.description.physicalpl
3953-3969
dc.description.pointspl
40
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
12
dc.identifier.doipl
10.3390/md12073953
dc.identifier.eissnpl
1660-3397
dc.identifier.projectpl
ROD UJ / P
dc.identifier.uri
http://ruj.uj.edu.pl/xmlui/handle/item/2544
dc.identifier.weblinkpl
https://www.mdpi.com/1660-3397/12/7/3953/htm
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Udzielam licencji. Uznanie autorstwa 3.0 Polska
dc.rights.licence
CC-BY
dc.rights.uri*
http://creativecommons.org/licenses/by/3.0/legalcode
dc.share.type
otwarte czasopismo
dc.subject.enpl
chitosan
dc.subject.enpl
coagulation
dc.subject.enpl
heparin antidote
dc.subject.enpl
hepatotoxicity
dc.subject.enpl
HTCC
dc.subject.enpl
protamine
dc.subject.enpl
unfractionated heparin
dc.subtypepl
Article
dc.titlepl
Inactivation of heparin by cationically modified chitosan
dc.title.journalpl
Marine Drugs
dc.typepl
JournalArticle
dspace.entity.type
Publication

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