Antitumour activity and adverse reactions of combined treatment with chitosan and doxorubicin in tumour-bearing mice

J Pharm Pharmacol. 2001 Oct;53(10):1373-8. doi: 10.1211/0022357011777873.

Abstract

We examined the antitumour activity and adverse reactions, such as myelotoxicity, gastrointestinal toxicity and body-weight loss,of the cancer chemotherapy drug doxorubicin when given with chitosan in sarcoma 180-bearing mice. Intraperitoneally administered doxorubicin (5 mg kg(-1)) given on days 1 and 8 with or without orally administered chitosan (200, 400 and 800 mg kg(-1) twice daily) inhibited tumour growth. The orally administered chitosan (400 and 800 mg kg(-1) twice daily) prevented doxorubicin-induced body-weight loss and small-intestinal mucosal injury. Similarly, the reduction of leucocyte number induced by the intraperitoneally administered doxorubicin was restored to normal by the oral administration of chitosan (400 and 800 mg kg(-1) twice daily). It seems likely that the mechanisms by which the orally administered chitosan protects against doxorubicin-induced gastrointestinal toxicity may be due to the formation of doxorubicin-chitosan complex in the small-intestinal mucosa through the diffusion of chitosan into the small-intestinal villi. In conclusion, our data suggest that the oral administration of chitosan prevents the gastrointestinal mucositis associated with doxorubicin therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / therapeutic use*
  • Body Weight / drug effects
  • Chitin / adverse effects
  • Chitin / analogs & derivatives
  • Chitin / therapeutic use*
  • Chitosan
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use*
  • Injections, Intraperitoneal
  • Intestinal Mucosa / enzymology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Organ Size
  • Sarcoma 180 / drug therapy*
  • Sucrase / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Chitin
  • Doxorubicin
  • Chitosan
  • Sucrase