Prophylactic treatment with vitamins C and B2 for methotrexate-induced gastrointestinal mucositis

dc.contributor.authorda Silva Ferreira, A.R.
dc.contributor.authorWardill, H.R.
dc.contributor.authorHavinga, R.
dc.contributor.authorTissing, W.J.E.
dc.contributor.authorHarmsen, H.J.M.
dc.date.issued2021
dc.description.abstractMucositis is a common side-effect of chemotherapy treatment, inducing alterations in the composition of the gut microbiota. Redox active compounds, such as vitamins B2 and C, have been shown to reduce inflammation and enhance the growth of anaerobic bacteria in the gut. We therefore aimed to (1) validate the ability of these compounds to promote bacterial cell growth in vitro, and (2) determine their prophylactic efficacy in a rat model of methotrexate (MTX)-induced mucositis. Bacterial growth curves were performed to assess the growth kinetics of bacteria exposed to Vitamins C and B2 (0.5 mM). Male wistar rats (150–200 g) received vitamins B2 (12 mg/day) and C (50 mg/day) via daily oral gavage (from day −1 to day 10). MTX (45 mg/Kg) was administrated via I.V. injection (N = 4–8/group) on day 0. Body weight, water/food consumption and diarrhea were assessed daily. Blood and faecal samples were collected longitudinally to assess citrulline levels (mucositis biomarker) and gut microbiota composition. Vitamins C/B2 enhanced the in vitro growth of anaerobic bacteria Blautia coccoides and Roseburia intestinalis. Contrarily to vitamin B2, in vivo administration of Vitamin C significantly attenuated clinical symptoms of mucositis. Despite their influence on the composition of the gut microbiota, both vitamins did not modulate the course of MTX-induced mucositis, as accessed by plasma citrulline. Vitamins B2 and C enhanced anaerobic bacterial growth in vitro, however their ability to mitigate MTX-induced mucositis was limited.
dc.description.statementofresponsibilityAna Rita da Silva Ferreira, Hannah R. Wardill, Rick Havinga, Wim J. E. Tissing and Hermie J. M. Harmsen
dc.identifier.citationBiomolecules, 2021; 11(1):1-15
dc.identifier.doi10.3390/biom11010034
dc.identifier.issn2218-273X
dc.identifier.issn2218-273X
dc.identifier.orcidWardill, H.R. [0000-0002-6613-3661]
dc.identifier.urihttp://hdl.handle.net/2440/129795
dc.language.isoen
dc.publisherMDPI
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/114092
dc.rights© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
dc.source.urihttps://doi.org/10.3390/biom11010034
dc.subjectChemotherapy-induced mucositis; methotrexate; gut microbiota; anaerobic bacteria; vitamin C; vitamin B2
dc.titleProphylactic treatment with vitamins C and B2 for methotrexate-induced gastrointestinal mucositis
dc.typeJournal article
pubs.publication-statusPublished

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