Skip to main content
Log in

Acute toxicity of high dosage carboxymethyl chitosan and its effect on the blood parameters in rats

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Khor E, Lim LY. Implantable application of chitin and chitosan. Biomaterials. 2003;24:2339–49.

    Article  CAS  Google Scholar 

  2. 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.

    Article  CAS  Google Scholar 

  3. 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.

    Article  Google Scholar 

  4. Muzzarelli RAA, Muzzarelli C. Chitosan chemistry: relevance to the biomedical sciences. Adv Polym Sci. 2005;186:151–209.

    Article  CAS  Google Scholar 

  5. 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.

    Article  Google Scholar 

  6. 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.

    Article  CAS  Google Scholar 

  7. 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.

    Article  Google Scholar 

  8. 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.

    Article  CAS  Google Scholar 

  9. 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.

    Article  CAS  Google Scholar 

  10. 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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  12. 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.

    Article  CAS  Google Scholar 

  13. 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.

    Article  CAS  Google Scholar 

  14. The United States Pharmacopeia (32nd ed)/National Formulary (27th ed) The United States Pharmacopeial Convention. 2009;981, 1030–1.

  15. 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.

    Article  Google Scholar 

  16. Wei W, Wu XM, Li YJ. Experimental methodology of pharmacology. 4th ed. Beijing: People’s Medical Publishing House; 2010. p. 1698.

    Google Scholar 

  17. 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.

    Google Scholar 

  18. Wang HL, Bao CX, Ruan CG. Thrombus and hemostasis assay techniques. Shanghai: Shanghai Scientific and Technical Publishers; 1992. p. 96–117.

    Google Scholar 

  19. 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.

    CAS  Google Scholar 

  20. Alexandre H, Eric R. Role of the coagulation/fibrinolysis system in fibrin-associated glomerular injury. J Am Soc Nephrol. 2004;15:844–53.

    Article  Google Scholar 

  21. Zhang JT. Modern experimental methods in pharmacology. Beijing: Beijing Medical University and China Concordance University Combined Press; 1997. p. 1209.

    Google Scholar 

  22. 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.

    Article  Google Scholar 

  23. Wolfgang K, Edzard E. The possible role of hemorheology in atherothrombogenesis. Atherosclerosis. 1992;94:93–107.

    Article  Google Scholar 

  24. Slack SM, Cui Y, Turitto VT. The effect of flow on blood coagulation and thrombosis. Thromb Haemost. 1993;70:129.

    CAS  Google Scholar 

  25. 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.

    Article  Google Scholar 

  26. 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.

    Article  CAS  Google Scholar 

Download references

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

Authors

Corresponding author

Correspondence to Wanshun Liu.

Rights and permissions

Reprints 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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-011-4467-4

Keywords

Navigation