Diamine Oxidase Activity As a Serum Biomarker for Intestinal Mucosal Damage, Appearance of Diarrhea and Malnutrition Due to Anticancer Drugs

Intestinal mucosal damage due to anticancer drugs which induces QOL impairment and malnutrition is one of major problems for cancer treatment. However, there is no method to evaluate objectively intestinal mucosal damage and malnutrition due to anticancer drugs. Diamine oxidase(DAO) is an enzyme which exists specifically in villi tips of enterocytes of the small intestine.

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  1. Miyoshi, H. Miyamoto, S. Matsumoto, Y. Fujino, K. Tanaka, F. Nakamura, M. Kagawa, T. Goji, S. Kitamura, N. Muguruma, T. Okahisa, T. Takayama.

2014 AGA Institute. Gastroenterology, Oficial Journal of the AGA Institute.321.

May 2014Volume 146, Issue 5, Supplement 1, Pages S-72–S-73

Aim:

Intestinal mucosal damage due to anticancer drugs which induces QOL impairment and malnutrition is one of major problems for cancer treatment. However, there is no method to evaluate objectively intestinal mucosal damage and malnutrition due to anticancer drugs. Diamine oxidase(DAO) is an enzyme which exists specifically in villi tips of enterocytes of the small intestine. Since DAO activity decreases as intestinal mucosa is damaged, it is expected that DAO activity is a good indicator which reflects sharply damage of small intestinal mucosa. The aim of this study is to investigate whether DAO activity is useful as an indicative marker for intestinal mucosal damage, appearance of diarrhea and malnutrition in patients with chemotherapy. Method:The subjects are 20 patients with unresectable advanced gastric cancer who received docetaxel, CDDP and S-1(DCS) combination chemotherapy (Takayama et al, Br J Cancer, 2008) as a first line chemotherapy.

DCS therapy is a modified regimen of docetaxel, CDDP and 5-FU combination chemotherapy, in which 5-FU was replaced by S-1. DAO activity was measured according to the methods of Takagiet al. (Clin Chim Acta, 1994) before, during and after chemotherapy. Mucosal atrophy is characterized by diminished intestinal function as well as morphological changes including decreased villous height, surface area(Shaw et al, World J Gastroenterol, 2012) and reduction in the number of goblet cells(Chang et al, World J Gastroenterol, 2005). Therefore, damage of small intestinal mucosa was evaluated by villous height, villous surface area and the number of goblet cells by endoscopic duodenum biopsies before and during chemotherapy.

Degree of diarrhea was evaluated by NCI-CTC V4.0. Nutrition was evaluated by serum albumin and serum total protein before, during and after chemotherapy. Results:The mean DAO activities(± SD) in 20 patients were 4.88±2.06U/L before chemotherapy, 2.96±1.62U/ L during chemotherapy(day14) and 3.66±1.27U/L after drug holiday(day21).

The DAO activity decreased significantly during chemotherapy and recovered significantly after drug holiday. Diarrhea(Grade1-3) appeared in 19 patients in the 10 to 18 day after administration of anticancer drugs and followed decrease in DAO activity. Villous height, villous surface area, the number of goblet cells were all significantly reduced by anticancer drugs and followed decrease in DAO activity. Serum albumin and serum total protein were significantly reduced by anticancer drugs and significantly increased after drug holiday. The DAO activity reduction rate between day1 and day14 was significantly correlated with albumin and total protein reduction rate between day1 and day21. Conclusion:Our results suggested that the DAO activity was useful as an indicative marker for intestinal mucosal damage, appearance of diarrhea and malnutrition in patients with chemotherapy.

DOI: https://doi.org/10.1016/S0016-5085(14)60262-6

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