Inactivation of Heparin by Cationically Modified Chitosan

Marine Drugs

Barbara Lorkowska-Zawicka³  Kamil Kamiński²  Justyna Ciejka²  Krzysztof Szczubiałka²  Magdalena Biaᐪs¹  Krzysztof Okoń¹  Dariusz Adamek¹  Maria Nowakowska²  Jacek Jawień³  Rafał Olszanecki³ 

[1] Department of Pathomorphology, Jagiellonian University Medical College, 16 Grzegórzecka Str., Cracow 31-531, Poland; E-Mails:;Faculty of Chemistry, Jagiellonian University, 3 Ingardena Str., Cracow 30-060, Poland; E-Mails:;Chair of Pharmacology, Jagiellonian University Medical College, 16 Grzegórzecka Str., Cracow 31-531, Poland; E-Mails:

关键词: chitosan;    HTCC;    unfractionated heparin;    heparin antidote;    protamine;    coagulation;    hepatotoxicity;   

DOI  :  10.3390/md12073953

来源: mdpi

【 摘 要 】

This study was performed to evaluate the ability of N-(2-hydroxypropyl)-3-trimethylammonium 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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.