Prevention by chitosan of myelotoxicity, gastrointestinal toxicity and immunocompetent organic toxicity induced by 5-fluorouracil without loss of antitumor activity in mice.
We examined the antitumor activity and side effects (myelotoxicity, immunocompetent organic toxicity and gastrointestinal toxicity) of combined treatment with the cancer chemotherapy drug 5-fluorouracil (5-FU) and dietary fiber chitosan in sarcoma 180-bearing mice. 5-FU (12.5 mg/kg x 2/day) plus chitosan (150, 375 and 750 mg/kg x 2/day) inhibited the tumor growth as well as 5-FU alone. Chitosan (150 and 750 mg/kg x 2/day) blocked the reduction of blood leukocyte number caused by 5-FU administration, and it prevented the injury of the small intestinal mucosa membrane and delayed the onset of diarrhea induced by 5-FU. Furthermore, chitosan (750 mg/kg x 2/day) prevented the reduction of spleen weight induced by 5-FU in sarcoma 180-bearing mice, and the reduction of lymphocyte and CD8+ T cell numbers induced by 5-FU was also prevented by the oral administration of chitosan (750 mg/kg x 2/day) in C57BL/6 mice. Chitosan (150 and/or 750 mg/kg x 2/day) reduced the 5-FU incorporation into RNA fractions of small intestine and spleen without affecting the 5-FU incorporation into the tumor in sarcoma 180-bearing mice. These findings suggest that prevention of the 5-FU side effects by chitosan might be partly due to the selective inhibition of 5-FU uptake into the small intestine and spleen, resulting in the reduction of immune function toxicity, myelotoxicity and gastrointestinal toxicity of 5-FU. Therefore, it is concluded that the combination of chitosan and 5-FU might be useful for the prevention of side effects such as gastrointestinal toxicity, immunotoxicity and myelotoxicity caused by 5-FU.
Kimura
Y
Y
2nd Department of Medical Biochemistry, School of Medicine, Ehime University. yokim@m.ehime-u.ac.jp
Okuda
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002686:Chitin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048271:Chitosan; D004064:Digestive System / Q000187:drug effects; D005472:Fluorouracil / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D007121:Immunocompetence / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D012334:RNA, Neoplasm / Q000378:metabolism; D012510:Sarcoma 180 / Q000188:drug therapy; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D000970:Antineoplastic Agents; D012334:RNA, Neoplasm; D002686:Chitin; D048271:Chitosan; D005472:Fluorouracil