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Gastrointestinal dysmotility in 5-fluorouracil-induced intestinal mucositis outlasts inflammatory process resolution

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Abstract

Aim

To evaluate gastrointestinal motility during 5-fluorouracil (5-FU)-induced intestinal mucositis.

Materials and methods

Wistar rats received 5-FU (150 mg kg−1, i.p.) or saline. After the 1st, 3rd, 5th, 15th and 30th day, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage, apoptotic and mitotic indexes, MPO activity and GSH concentration. In order to study gastrointestinal motility, on the 3rd or 15th day after 5-FU treatment, gastric emptying in vivo was measured by scintilographic method, and stomach or duodenal smooth muscle contractions induced by CCh were evaluated in vitro.

Results

On the third day of treatment, 5-FU induced a significant villi shortening, an increase in crypt depth and intestinal MPO activity and a decrease in villus/crypt ratio and GSH concentration. On the first day after 5-FU there was an increase in the apoptosis index and a decrease in the mitosis index in all intestinal segments. After the 15th day of 5-FU treatment, a complete reversion of all these parameters was observed. There was a delay in gastric emptying in vivo and a significant increase in gastric fundus and duodenum smooth muscle contraction, after both the 3rd and 15th day.

Conclusion

5-FU-induced gastrointestinal dysmotility outlasts intestinal mucositis.

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Acknowledgments

The authors gratefully acknowledge the financial support from CNPq (Brazil) and the technical assistance of Maria Silvandira Freire França. Drs. Brito, Oliveira, Ribeiro, Santos, Assreuy and Souza, who are recipients of CNPq fellowship. Dr. G. Ostrov provided English language editing of manuscript. This work is part of the requirements to obtain a PhD degree in Pharmacology at Federal University of Ceará—UFC School of Medicine, by one of us (PMG Soares).

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Authors and Affiliations

  1. Centro de Biomedicina, Faculdade de Medicina, Universidade Federal do Ceará, Rua Cel. Nunes de Melo, 1315, Rodolfo Teófilo, Fortaleza-CE, 60.430-270, Brazil

    Pedro M. G. Soares, José Maurício S. C. Mota, Antoniella S. Gomes, Gerly Anne C. Brito, Armênio A. Santos, Ronaldo A. Ribeiro & Marcellus H. L. P. Souza

  2. Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil

    Ricardo B. Oliveira

  3. Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza-CE, Brazil

    Ana Maria S. Assreuy

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  1. Pedro M. G. Soares
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  2. José Maurício S. C. Mota
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Correspondence to Marcellus H. L. P. Souza.

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Soares, P.M.G., Mota, J.M.S.C., Gomes, A.S. et al. Gastrointestinal dysmotility in 5-fluorouracil-induced intestinal mucositis outlasts inflammatory process resolution. Cancer Chemother Pharmacol 63, 91–98 (2008). https://doi.org/10.1007/s00280-008-0715-9

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  • DOI: https://doi.org/10.1007/s00280-008-0715-9

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