Attenuation of Doxorubicin-Induced Small Intestinal Mucositis by Pectins is Dependent on Pectin's Methyl-Ester Number and Distribution

Martin Beukema*, Eva Jermendi, Taco Koster, Kohji Kitaguchi, Bart J. de Haan, Marco Alexander van den Berg, Marijke M. Faas, Henk A. Schols, Paul de Vos

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article number2100222
Number of pages8
JournalMolecular Nutrition & Food Research
DOIs
Publication statusE-pub ahead of print - 7-Aug-2021

Keywords

  • chemotherapy
  • degree of blockiness
  • degree of methyl-esterification
  • doxorubicin
  • mucositis
  • pectin
  • RECEPTORS
  • THERAPY
  • IMPACT
  • TLR-2

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