Abstract
This experiment was aimed to study whether Carboxymethyl chitosan has acute toxicity and effects on the blood parameters of rats, which were treated with high dosage carboxymethyl chitosan (1350 mg/kg) through a laparotomy. Acute toxicity was first studied and then kinds of blood parameters were detected at different time points after the laparotomy, which contain coagulant parameters (thrombin time, prothrombin time, activated partial thromboplatin time and fibrinogen), anticoagulant parameter (antithrombin III), fibrinolytic parameters (plasminogen and fibrin degradation product) and hemorheology parameters (blood viscosity). Results showed that no acute toxicity was detected and no significant effects were found on the parameters of coagulation, anticoagulation, fibrinolysis or hemorheology of rats after the laparotomy, which indicated that carboxymethyl chitosan has no significant toxicity on the blood system of rats after being absorbed in the abdominal cavity and degraded gradually in the blood. And this study has provided experimental basis for carboxymethyl chitosan to be applied in the field of biomedical materials.
Similar content being viewed by others
References
Khor E, Lim LY. Implantable application of chitin and chitosan. Biomaterials. 2003;24:2339–49.
Zhong ZM, Li PC, Xing RE, Liu S. Antimicrobial activity of hydroxylbenzenesulfonailides derivatives of chitosan, chitosan sulfates and carboxymethyl chitosan. Int J Biol Macromol. 2009;45:163–8.
Mistra S, Gaur U, Ghosh PC, Maitra AN. Tumour targeted delivery of encapsulated dextran-doxorubicin conjugate using chitosan nanoparticles as carrier. J Control Release. 2001;74:317–23.
Muzzarelli RAA, Muzzarelli C. Chitosan chemistry: relevance to the biomedical sciences. Adv Polym Sci. 2005;186:151–209.
Yilqor P, Tuzlakoqlu K, Reis RL. Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering. Biomaterials. 2009;30:3551–9.
Lu GY, Kong LJ, Sheng BY, Wang G, Gong YD, Zhang XF. Degradation of covalently cross-linked carboxymethyl chitosan and its potential application for peripheral nerve regeneration. Eur Polym J. 2007;43:3807–18.
Darren J, Costain BS, Renee KMD, Curtis CMD, Vivian C, McAlister MD, Timothy DGL. Prevention of postsurgical adhesions with N,O-carboxymethyl chitosan: examination of the most efficacious preparation and the effect of N,O-carboxymethyl chitosan on postsurgical healing. Surgery. 1997;121:314–9.
Chen SC, Wu YC, Mi FL, Lin YH, Yu LC, Sung HW. A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery. J Control Release. 2004;96:285–300.
Shi ZL, Neoh KG, Kang ET, Poh CK, Wang W. Surface functionalization of titanium with carboxymethyl chitosan and immobilized bone morphogenetic protein-2 for enhanced osseointegration. Biomacromolecules. 2009;10:1603–11.
Juan Z, Clive E, Timothy DGL. Reduction in postoperative adhesion formation, re-formation after an abdominal operation with the use of N,O-carboxymethyl chitosan. Surgery. 2004;135:307–11.
Yang J, Tian F, Wang Z, Wang Q, Zeng YJ, Chen SQ. Effect of chitosan molecular weight and deacetylation degree on hemostasis. J Biomed Mater Res Part B Appl Biomater. 2008;84B:131–7.
Dong W, Han BQ, Feng YL, Song FL, Chang J, Jiang HP, Tang YY, Liu WS. Pharmacokinetics and biodegradation mechanisms of versatile carboxymethyl derivative of chitosan in rats: in vivo and in vitro evaluation. Biomacromolecules. 2010;11:1527–33.
Fu DW, Han BQ, Dong W, Yang Z, Lv Y, Liu WS. Effects of carboxymethyl chitosan on the blood system of rats. Biochem Biophys Res Commun. 2011;408:110–4.
The United States Pharmacopeia (32nd ed)/National Formulary (27th ed) The United States Pharmacopeial Convention. 2009;981, 1030–1.
Jean YR, Rita D, Lucio CR, Richard LL, Eric L, Olivier B, Giampaolo G, Yves H, Jane ED, Christiane G. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomized, placebo-controlled clinical trial. Lancet. 2001;357:251–6.
Wei W, Wu XM, Li YJ. Experimental methodology of pharmacology. 4th ed. Beijing: People’s Medical Publishing House; 2010. p. 1698.
Wang ZY, Li JZ, Ruan CG. Thrombus and hemostasis: basic theory and clinic. 2nd ed. Shanghai: Shanghai Scientific and Technical Publishers; 1992. p. 61–90.
Wang HL, Bao CX, Ruan CG. Thrombus and hemostasis assay techniques. Shanghai: Shanghai Scientific and Technical Publishers; 1992. p. 96–117.
Christe M, Fritschi J, Lammle B, Tran TH, Marbet GA, Berger W, Duckert F. Fifteen coagulation and fibrinolysis parameters in diabetes mellitus and in patients with vasculopathy. Thromb Haemost. 1984;52:138–43.
Alexandre H, Eric R. Role of the coagulation/fibrinolysis system in fibrin-associated glomerular injury. J Am Soc Nephrol. 2004;15:844–53.
Zhang JT. Modern experimental methods in pharmacology. Beijing: Beijing Medical University and China Concordance University Combined Press; 1997. p. 1209.
Cicco MD, Matovic M, Balestreri L, Angelis VD, Fracasso A, Morassut S, Coran F, Babare R, Buonadonna A, Testa V. Antithrombin III deficiency as a risk factor for catheter-related central vein thrombosis in cancer patients. Thrombosis Res. 1995;78:127–37.
Wolfgang K, Edzard E. The possible role of hemorheology in atherothrombogenesis. Atherosclerosis. 1992;94:93–107.
Slack SM, Cui Y, Turitto VT. The effect of flow on blood coagulation and thrombosis. Thromb Haemost. 1993;70:129.
Zhang JF, Paul CJ, Aleksander SP. Red blood cell aggregation and dissociation in shear flows simulate by lattice Boltzmann method. J Biomech. 2008;41:47–55.
Zanazzi M, Fatini C, Farsetti S, Rosso G, Caroti L, Sticchi E, Liotta AA, Ricci I, Mannini L, Bertoni E, Abbate R, Salvadori M. Blood rheology and renal transplantation: an intriguing relationship for assessing cardiovascular risk. Transplant Proc. 2010;42:1383–4.
Acknowledgments
This work is supported by the National High Technology Research and Development Program of China (863 Program, grant number: 2006AA02A132, 2007AA091603).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yang, Z., Han, B., Fu, D. et al. Acute toxicity of high dosage carboxymethyl chitosan and its effect on the blood parameters in rats. J Mater Sci: Mater Med 23, 457–462 (2012). https://doi.org/10.1007/s10856-011-4467-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10856-011-4467-4