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

Department of Surgery, Chi-Mei Foundational Medical Center Yung-Kang City, Tainan, Taiwan, Department of Biotechnology, Southern Taiwan University, Taiwan, Department of Surgery, Taipei Medical University, Taipei, Taiwan

Ying-Jan Wang

Department of Environmental and Occupational Health National Cheng Kung University, Medical College, Tainan, Taiwan

Town-Ming Hsu

Department of Environmental and Occupational Health National Cheng Kung University, Medical College, Tainan, Taiwan

Mei-Huei Chen

Bioresource Collection and Research Center, Food Industry Research and Development Institute, Taiwan

Hing-Yuen Chan

Bioresource Collection and Research Center, Food Industry Research and Development Institute, Taiwan

Yuan-Soon Ho

Graduate Institute of Biomedical Technology Taipei Medical University, Taipei, Taiwan

Shyr-Yi Lin

Department of Internal Medicine and Primary Care Medicine School of Medicine, Taipei Medical University and Hospital, Taipei, Taiwan, sylin{at}tmu.edu.tw

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.

Key Words: cancer chemotherapy • chitosan • 5-fluorouracil • cytotoxicity • comet assay.

Journal of Bioactive and Compatible Polymers, Vol. 23, No. 5, 458-472 (2008)
DOI: 10.1177/0883911508095840


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