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Role of Capsaicin-Sensitive Primary Afferent Neurons and Non-protein Sulphydryl Groups on Gastroprotective Effect of Amifostine Against Ethanol-Induced Gastric Damage in Rats

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Abstract

Background

Amifostine has been widely tested as a cytoprotective agent against a number of aggressors in different organs. Recently, a gastroprotective effect was observed for this drug in a model of indomethacin-induced gastric injury. Our objective was to investigate the effect of amifostine on ethanol-induced gastric injury and the role played in this mechanism by afferent sensory neurons, non-protein sulfhydryl groups, nitric oxide, ATP-sensitive potassium channels, and cyclooxygenase-2.

Methods

Rats were treated with amifostine (22.5, 45, 90, or 180 mg/kg, PO or SC). After 30 min, the rats received absolute ethanol (5 ml kg−1, PO). One hour later, gastric damage was quantified with a planimeter. Samples from the stomach were also taken for histopathological assessment and for assays of non-protein sulfhydryl groups. The other groups were pretreated with L-NAME (10 mg kg−1, IP), glibenclamide (10 mg kg−1, PO), or celecoxib (10 mg kg−1, PO). After 30 min, the animals were given amifostine (90 mg kg−1, PO or SC), followed 30 min later by gavage with absolute ethanol (5 ml kg−1). Other rats were desensitized with capsaicin (125 mg kg−1, SC) 8 days prior to amifostine treatment.

Results

Amifostine administration PO and SC significantly and dose-dependently reduced ethanol-induced macroscopic and microscopic gastric damage by restoring glutathione levels in the stomach mucosa. Amifostine-promoted gastroprotection against ethanol-induced stomach injury was reversed by pretreatment with neurotoxic doses of capsaicin, but not by L-NAME, glibenclamide, or celecoxib.

Conclusions

Amifostine protects against ethanol-induced gastric injury by increasing glutathione levels and stimulating the afferent sensory neurons in the stomach.

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Acknowledgments

The authors would like to thank Maria Silvandira Freire França and José Ivan Rodrigues for their technical assistance. This study was supported by grants from CNPq (Brazil). Dr. Ribeiro, Dr. Brito, and Dr. Souza are CNPq fellowship holders. This study is part of the requirements for coauthor J. J. Junqueira to obtain a Master of Science degree in Pharmacology from the Medical School at the Federal University of Ceará.

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Authors and Affiliations

  1. Brazilian Semi-Arid Institute of Biomedicine (INCT-IBISAB), Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Rua Cel. Nunes de Melo, 1315, Rodolfo Teófilo, Fortaleza, CE, 60430-270, Brazil

    Jerônimo Junqueira-Júnior, Ana Flávia Torquato Araújo Junqueira, Jand Venes R. Medeiros, Sergio Henrique Brito Barbosa, Ana Carolina Pereira Nogueira, José Maurício Segundo Correia Mota, Ana Paula Macêdo Santana, Gerly Anne C. Brito, Ronaldo A. Ribeiro, Roberto César P. Lima-Júnior & Marcellus H. L. P. Souza

  2. Department of Biology, Federal University of Piaui, Minister Reis Velloso campus, Av. São Sebastião, 2819, Parnaiba, PI, 64202-020, Brazil

    Jand Venes R. Medeiros

  3. Centro de Biomedicina, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brazil

    Marcellus H. L. P. Souza

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  1. Jerônimo Junqueira-Júnior
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  2. Ana Flávia Torquato Araújo Junqueira
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  8. Gerly Anne C. Brito
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  9. Ronaldo A. Ribeiro
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  10. Roberto César P. Lima-Júnior
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  11. Marcellus H. L. P. Souza
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Correspondence to Marcellus H. L. P. Souza.

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Junqueira-Júnior, J., Junqueira, A.F.T.A., Medeiros, J.V.R. et al. Role of Capsaicin-Sensitive Primary Afferent Neurons and Non-protein Sulphydryl Groups on Gastroprotective Effect of Amifostine Against Ethanol-Induced Gastric Damage in Rats. Dig Dis Sci 56, 314–322 (2011). https://doi.org/10.1007/s10620-010-1300-8

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  • DOI: https://doi.org/10.1007/s10620-010-1300-8

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