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Publication : Prevention by chitosan of myelotoxicity, gastrointestinal toxicity and immunocompetent organic toxicity induced by 5-fluorouracil without loss of antitumor activity in mice.

First Author  Kimura Y Year  1999
Journal  Jpn J Cancer Res Volume  90
Issue  7 Pages  765-74
PubMed ID  10470290 Mgi Jnum  J:56694
Mgi Id  MGI:1342188 Doi  10.1111/j.1349-7006.1999.tb00813.x
Citation  Kimura Y, et al. (1999) Prevention by chitosan of myelotoxicity, gastrointestinal toxicity and immunocompetent organic toxicity induced by 5-fluorouracil without loss of antitumor activity in mice. Jpn J Cancer Res 90(7):765-74
abstractText  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.
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