期刊
MOLECULAR NUTRITION & FOOD RESEARCH
卷 65, 期 18, 页码 -出版社
WILEY
DOI: 10.1002/mnfr.202100222
关键词
chemotherapy; degree of blockiness; degree of methyl-esterification; doxorubicin; mucositis; pectin
资金
- Agrifirm Innovation Center B.V.
- Cooperatie Avebe U.A.
- DSM Food Specialties B.V.
- VanDrie Holding N.V.
Intestinal mucositis induced by doxorubicin can be prevented by dietary fiber pectin through direct inhibition of TLR2. The degree of methyl-esterification and blockiness of pectins determine their efficacy in attenuating doxorubicin-induced intestinal mucositis. Pectin structures with stronger TLR2-inhibiting properties may prevent the development of doxorubicin-induced intestinal damage in chemotherapy patients.
Scope Intestinal mucositis is a common side effect of the chemotherapeutic agent doxorubicin, which is characterized by severe Toll-like receptor (TLR) 2-mediated inflammation. The dietary fiber pectin is shown to prevent this intestinal inflammation through direct inhibition of TLR2 in a microbiota-independent manner. Recent in vitro studies show that inhibition of TLR2 is determined by the number and distribution of methyl-esters of pectins. Therefore, it is hypothesized that the degree of methyl-esterification (DM) and the degree of blockiness (DB) of pectins determine attenuating efficacy on doxorubicin-induced intestinal mucositis. Methods and Results Four structurally different pectins that differed in DM and DB are tested on inhibitory effects on murine TLR2 in vitro, and on doxorubicin-induced intestinal mucositis in mice. These data demonstrate that low DM pectins or intermediate DM pectins with high DB have the strongest inhibitory impact on murine TLR2-1 and the strongest attenuating effect on TLR2-induced apoptosis and peritonitis. Intermediate DM pectin with a low DB is, however, also effective in preventing the induction of doxorubicin-induced intestinal damage. Conclusion These pectin structures with stronger TLR2-inhibiting properties may prevent the development of doxorubicin-induced intestinal damage in patients undergoing chemotherapeutic treatment with doxorubicin.
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