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Oral Supplementation of Butyrate Reduces Mucositis and Intestinal Permeability Associated with 5-Fluorouracil Administration

  • Original Article
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Lipids

Abstract

Mucositis affects about 40 % of patients undergoing chemotherapy. Short chain fatty acids (SCFA), mainly butyrate, are claimed to improve mucosal integrity, reduce intestinal permeability and act as anti-inflammatory agents for the colon mucosa. We evaluated the effects of oral administration of SCFA or butyrate in the 5FU-induced mucositis. Mice received water, SCFA or butyrate during all experiment (10 days) and a single dose of 5FU (200 mg/kg) 3 days before euthanasia. We evaluated inflammatory and histological score by morphometry, and by activity of enzymes specific to neutrophil, eosinophil and macrophage and TLR-4, TNF-alpha and IL6 expressions. Intestinal permeability and tight junction protein ZO-1 expression were evaluated. Mice from the 5FU (5-Fluorouracil) group presented weight loss, ulcerations and inflammatory infiltration of neutrophils and eosinophils, increased expression of IL6 and TNF-alpha and increased intestinal permeability. SCFA minimized intestinal damage, reduced ulcerations without affecting intestinal permeability. Butyrate alone was more efficient at improving those parameters than in SCFA solution and also reduced intestinal permeability. The expression of pro-inflammatory cytokines and ZO-1 tended to be higher in the SCFA supplemented but not in the butyrate supplemented group. We showed the beneficial effects of butyrate on intestinal mucositis and its promising function as an adjuvant in the treatment of diseases not only of the colon, but also of the small intestine.

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Abbreviations

5FU:

5-Fluorouracil

CCL2/MCP-1:

Monocyte chemotactic protein-1

DMSO:

Dimethyl sulfoxide

DTPA:

Diethyleneaminopentacetic acid

EPO:

Eosinophil peroxidase

GLP-2:

Glucagon-like peptide-2

MCT:

Monocarboxylate transporters

MPO:

Myeloperoxidase

NAG:

N-Acetylglucosaminidase

SCFA:

Short-chain fatty acid

TJ:

Tight junctions

(ZO)-1:

Zonula occludens-1

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Acknowledgments

This study was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq); Coordenação de Aperfeiçoamento de Nível Superior (CAPES), Fundação de Amparo a Pesquisa de Minas Gerais (FAPEMIG) e Pro-Reitoria de Pesquisa (PRPq) da UFMG. The authors are grateful to Maria Helena Alves, for taking care of the animals.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil

    Talita Mayra Ferreira, Alda Jusceline Leonel, Marco Antônio Melo & Jacqueline I. Alvarez-Leite

  2. Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil

    Rosana R. G. Santos, Denise Carmona Cara & Valbert N. Cardoso

  3. Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil

    Talita Mayra Ferreira, Alda Jusceline Leonel, Marco Antônio Melo, Rosana R. G. Santos, Denise Carmona Cara, Valbert N. Cardoso, Maria I. T. D. Correia & Jacqueline I. Alvarez-Leite

  4. Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil

    Maria I. T. D. Correia

  5. Universidade Federal de Minas Gerais, Caixa Postal 486, Belo Horizonte, CEP 30161-970, Brazil

    Jacqueline I. Alvarez-Leite

Authors
  1. Talita Mayra Ferreira
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  2. Alda Jusceline Leonel
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  3. Marco Antônio Melo
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  4. Rosana R. G. Santos
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  5. Denise Carmona Cara
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  6. Valbert N. Cardoso
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  7. Maria I. T. D. Correia
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  8. Jacqueline I. Alvarez-Leite
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Corresponding author

Correspondence to Jacqueline I. Alvarez-Leite.

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Ferreira, T.M., Leonel, A.J., Melo, M.A. et al. Oral Supplementation of Butyrate Reduces Mucositis and Intestinal Permeability Associated with 5-Fluorouracil Administration. Lipids 47, 669–678 (2012). https://doi.org/10.1007/s11745-012-3680-3

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  • DOI: https://doi.org/10.1007/s11745-012-3680-3

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