Effects of Fungal-derived High Molecular Weight Chitosan on 5-Fluorouracil-induced Adverse Reactions

The effects of fungal-derived high molecular weight chitosan (HMWC) on the prevention of 5-fluorouracil (5-FU)-induced side-effects were studied in a sarcoma-bearing mice model. 5-FU (12.5mg/kg) was gargled into the mice with or without HMWC (25, 75, and 150mg/kg) every 12 h for consecutive 8 or 16 days in different experiments. The HMWC (25—150 mg/kg) exerted no toxicity and did not interfere with the anti-tumor activity of 5-FU on sarcoma-bearing mice. HMWC in a higher dose (150 mg/kg) partially protected 5-FU-induced cytotoxicity on peripheral leukocytes, lymphocytes, and bone marrow CD-19 positive cells. HMWC reversed the 5-FU suppression of intestine sucrase activity and attenuated the 5-FU-induced diarrhea. Bone marrow cells micronucleus and DNA comet assays demonstrated that HMWC significantly reversed 5-FU-induced genome toxicity to marrow cells. These results suggested that fungal-derived HMWC attenuated the 5-FU-induced bone marrow and gastrointestinal toxicity, and has the potential for clinical applications in the future.