Antitumour activity and adverse reactions of combined treatment with chitosan and doxorubicin in tumour-bearing mice.
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.
Kimura
Y
Y
Second Department of Medical Biochemistry, School of Medicine, Ehime University, Onsen-gun, Japan. yokim@m.ehime-u.ac.jp
Sawai
N
N
Okuda
H
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002686:Chitin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D048271:Chitosan; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size; D012510:Sarcoma 180 / Q000188:drug therapy*; D013393:Sucrase / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D002686:Chitin; D004317:Doxorubicin; D048271:Chitosan; D013393:Sucrase