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Regulatory role of Lactobacillus acidophilus on inflammation and gastric dysmotility in intestinal mucositis induced by 5-fluorouracil in mice

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Abstract

Purpose

Lactobacillus acidophilus is widely used for gastrointestinal disorders, but its role in inflammatory conditions like in chemotherapy-induced mucositis is unclear. Here, we report the effect of L. acidophilus on 5-fluorouracil-induced (5-FU) intestinal mucositis in mice.

Methods

Mice weighing 25–30 g (n = 8) were separated into three groups, saline, 5-FU, and 5-FU + L. acidophilus (5-FU-La) (16 × 109 CFU/kg). In the 5-FU-La group, L. acidophilus was administered concomitantly with 5-FU on the first day and alone for two additional days. Three days after the last administration of L. acidophilus, the animals were euthanized and the jejunum and ileum were removed for histopathological assessment and for evaluation of levels of myeloperoxidase activity, sulfhydryl groups, nitrite, and cytokines (TNF-α, IL-1β, CXCL-1, and IL-10). In addition, we investigated gastric emptying using spectrophotometry after feeding a 1.5-ml test meal by gavage and euthanasia. Data were submitted to ANOVA and Bonferroni’s test, with the level of significance at p < 0.05.

Results

Intestinal mucositis induced by 5-FU significantly (p < 0.05) reduced the villus height–crypt depth ratio and GSH concentration and increased myeloperoxidase activity and the nitrite concentrations compared with the control group. Furthermore, 5-FU significantly (p < 0.05) increased cytokine (TNF-α, IL-1β, and CXCL-1) concentrations and decreased IL-10 concentrations compared with the control group. 5-FU also significantly (p < 0.05) delayed gastric emptying and gastrointestinal transit compared with the control group. All of these changes were significantly (p < 0.05) reversed by treatment with L. acidophilus.

Conclusions

Lactobacillus acidophilus improves the inflammatory and functional aspects of intestinal mucositis induced by 5-FU.

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Acknowledgments

The authors would like to thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP) for financial support and Maria Silvandira Freire França for technical assistance. Dr. Ribeiro, Dr. Souza, and Dr. Soares are CNPq fellowship holders.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Medical School, Federal University of Ceara, Rua Cel. Nunes de Melo 1315, Rodolfo Teofilo, Fortaleza, Ceara, CEP 60.430-270, Brazil

    Priscilla F. C. Justino, Luis F. M. Melo, Andre F. Nogueira, Cecila M. Morais, Walber O. Mendes, Alvaro X. Franco, Ronaldo A. Ribeiro, Marcellus H. L. P. Souza & Pedro Marcos Gomes Soares

  2. Department of Morphology, Medical School, Federal University of Ceara, Rua Delmiro de Farias s/n, Rodolfo Teofilo, Fortaleza, Ceara, CEP 60.416-030, Brazil

    Emmanuel P. Souza & Pedro Marcos Gomes Soares

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  1. Priscilla F. C. Justino
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  2. Luis F. M. Melo
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  3. Andre F. Nogueira
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  4. Cecila M. Morais
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  6. Alvaro X. Franco
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  8. Ronaldo A. Ribeiro
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  9. Marcellus H. L. P. Souza
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Correspondence to Pedro Marcos Gomes Soares.

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Justino, P.F.C., Melo, L.F.M., Nogueira, A.F. et al. Regulatory role of Lactobacillus acidophilus on inflammation and gastric dysmotility in intestinal mucositis induced by 5-fluorouracil in mice. Cancer Chemother Pharmacol 75, 559–567 (2015). https://doi.org/10.1007/s00280-014-2663-x

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