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

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.

• Authors: Martin Beukema, Éva Jermendi, Taco Koster, Kohji Kitaguchi, Bart J de Haan, Marco Alexander van den Berg, Marijke M Faas, Henk A Schols, Paul de Vos
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 65 Issue 18 Pg. e2100222 (09 2021) ISSN: 1613-4133 [Electronic] Germany
• PMID: 34268870 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antibiotics, Antineoplastic
• Tlr2 protein, mouse
• Toll-Like Receptor 2
• Doxorubicin
• Pectins

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, chemistry, pharmacology)
• Antibiotics, Antineoplastic (adverse effects)
• Apoptosis (drug effects)
• Cell Line
• Dose-Response Relationship, Drug
• Doxorubicin (adverse effects)
• Esterification
• Female
• Intestinal Diseases (chemically induced, drug therapy, pathology)
• Intestinal Mucosa (drug effects)
• Intestine, Small (drug effects, pathology)
• Mice, Inbred C57BL
• Mucositis (chemically induced, drug therapy, pathology)
• Pectins (administration & dosage, chemistry, pharmacology)
• Peritonitis (chemically induced, drug therapy, pathology)
• Structure-Activity Relationship
• Toll-Like Receptor 2 (antagonists & inhibitors, metabolism)
• Mice