Chitosan gastrointestinal toxicity

Fig. 8. The preventive effects of chitosan on doxorubicin-induced gastrointestinal toxicity in sarcoma 180-beanng mice, a) small intestine weight b) sucrase activity in small intestinal mucosa.

Gastrointestinal toxicity and myelotoxicity are caused by the 5-FU after its phosphorylation in the digestive tract and bone marrow tissue. To clarify whether chitosan enhances the antitumor activity of 5-FU and prevents the side effects induced by 5-FU, we examined the antitumor activity and side effects, such as myelotoxicity, immimocompetent organ toxicity, and gastrointestinal toxicity of combined treatment with chitosan and 5-FU in sarcoma 180-beaiing mice. 

Fig. (55). Inhibitory effects of chitosan on gastrointestinal toxicity (reduction of sucrase activity in small intestinal mucosa) induced by 5-FU in sarcoma 180-bearing mice.

Y. Kimura, and H. Okuda, 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), 765-774,1999. 

Chitosan is totally non-toxic and its degradation products namely glucosamines are biocompatible. Although the gastrointestinal enzymes can partially degrade both chitin and chitosan, when both polymers are orally administered, they are not absorbed. Chitosan shows a LD50 of around 16 g/kg, very similar to the salt and glucose values in assays carried out on mice [1, 73]. Toxicity of chitosan is reported to depend on DAC, which decreases with increase in DAC. On the other hand, Mw of chitosan did not influence toxicity [73]. 

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