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Amifostine (Wr-2721) Prevents Indomethacin-Induced Gastric Damage in Rats: Role of Non-Protein Sulfhydryl Groups and Leukocyte Adherence

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Abstract

This study was designed to evaluate the protective effect of amifostine on indomethacin-induced gastric damage, and the role of increased gastric non-protein sulfhydryl groups (NP-SH) and decreased leukocyte adherence in this event. Wistar rats were pretreated with amifostine (10, 30, or 90 mg/kg intraperitoneal (i.p.) or subcutaneous (s.c.)) or saline. After 30 min, the rats received indomethacin (20 mg/kg, by gavage) and were then killed 3 hr later. Macroscopic and microscopic gastric damage, concentration of gastric NP-SH, prostaglandin E2 (PGE2), and mesenteric leukocyte adherence (intravital microscopy) were assessed. Amifostine prevented significantly (P < 0.05), macroscopic or microscopic, indomethacin-induced gastric damage, and increased gastric NP-SH, in a dose-dependent manner, with a maximal effect at a dose of 90 mg/kg. Subcutaneous, but not i.p., amifostine administration decreased (P < 0.05) the indomethacin-induced increase in leukocyte adherence. Indomethacin-induced PGE2 depletion was not reversed by amifostine. Amifostine has a protective effect against indomethacin-induced gastropathy by increasing gastric NP-SH and decreasing leukocyte adherence.

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Acknowledgements

We are grateful for the technical assistance of Maria Silvandira Freire and José Ivan Rodrigues of the Federal University of Ceará. We also thank Dr. Albert Leyva for assistance.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil

    José Maurício S. C. Mota, Pedro M. G. Soares, Álvaro A. J. Menezes, Ronaldo A. Ribeiro & Marcellus H. L. P. de Souza

  2. Department of Pharmacology, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirão Preto, São Paulo, Brazil

    Henrique P. Lemos & Fernando Q. Cunha

  3. Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil

    Gerly Anne C. Brito

  4. Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1127, Rodolfo Teófilo, Fortaleza-CE, CEP: 60.430-270, Brazil

    Marcellus H. L. P. de Souza

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  1. José Maurício S. C. Mota
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  2. Pedro M. G. Soares
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  4. Henrique P. Lemos
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  5. Fernando Q. Cunha
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  6. Gerly Anne C. Brito
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  7. Ronaldo A. Ribeiro
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  8. Marcellus H. L. P. de Souza
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Correspondence to Marcellus H. L. P. de Souza.

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Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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Mota, J.M.S.C., Soares, P.M.G., Menezes, Á.A.J. et al. Amifostine (Wr-2721) Prevents Indomethacin-Induced Gastric Damage in Rats: Role of Non-Protein Sulfhydryl Groups and Leukocyte Adherence. Dig Dis Sci 52, 119–125 (2007). https://doi.org/10.1007/s10620-006-9496-3

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  • DOI: https://doi.org/10.1007/s10620-006-9496-3

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