title: Prevention by chitosan of myelotoxicity, gastrointestinal toxicity and immunocompetent organic toxicity induced by 5-fluorouracil without loss of antitumor activity in mice.
abstract: 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.
authors.affiliation: 2nd Department of Medical Biochemistry, School of Medicine, Ehime University. yokim@m.ehime-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Okuda
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D012334:RNA, Neoplasm; D002686:Chitin; D048271:Chitosan; D005472:Fluorouracil