title: Inactivation of heparin by cationically modified chitosan.
abstract: 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.
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, 16 Grzegórzecka Str., Cracow 31-531, Poland. mfziemia@cyf-kr.edu.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lorkowska-Zawicka
authors.affiliation: Faculty of Chemistry, Jagiellonian University, 3 Ingardena Str., Cracow 30-060, Poland. kaminski@chemia.uj.edu.pl.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kamiński
authors.affiliation: Faculty of Chemistry, Jagiellonian University, 3 Ingardena Str., Cracow 30-060, Poland. justyna.ciejka@gmail.com.
authors.forename: Justyna
authors.initials: J
authors.lastname: Ciejka
authors.affiliation: Faculty of Chemistry, Jagiellonian University, 3 Ingardena Str., Cracow 30-060, Poland. szczubia@chemia.uj.edu.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szczubiałka
authors.affiliation: Department of Pathomorphology, Jagiellonian University Medical College, 16 Grzegórzecka Str., Cracow 31-531, Poland. mbialas7@gmail.com.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Białas
authors.affiliation: Department of Pathomorphology, Jagiellonian University Medical College, 16 Grzegórzecka Str., Cracow 31-531, Poland. mpokon@cyf-kr.edu.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Okoń
authors.affiliation: Department of Pathomorphology, Jagiellonian University Medical College, 16 Grzegórzecka Str., Cracow 31-531, Poland. mnadamek@cyf-kr.edu.pl.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Adamek
authors.affiliation: Faculty of Chemistry, Jagiellonian University, 3 Ingardena Str., Cracow 30-060, Poland. nowakows@chemia.uj.edu.pl.
authors.forename: Maria
authors.initials: M
authors.lastname: Nowakowska
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, 16 Grzegórzecka Str., Cracow 31-531, Poland. mmjawien@cyf-kr.edu.pl.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jawień
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, 16 Grzegórzecka Str., Cracow 31-531, Poland. mfolszan@cyf-kr.edu.pl.
authors.forename: Rafał
authors.initials: R
authors.lastname: Olszanecki
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, 16 Grzegórzecka Str., Cracow 31-531, Poland. mfkorbut@cyf-kr.edu.pl.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Korbut
mesh_terms: D000818:Animals; D048271:Chitosan / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006494:Heparin Antagonists / Q000494:pharmacology* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D010314:Partial Thromboplastin Time; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006494:Heparin Antagonists; D048271:Chitosan