caa a22 4500 445797355 CHVBK 20180317145130.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10620-010-1300-8 doi (NATIONALLICENCE)springer-10.1007/s10620-010-1300-8 Role of Capsaicin-Sensitive Primary Afferent Neurons and Non-protein Sulphydryl Groups on Gastroprotective Effect of Amifostine Against Ethanol-Induced Gastric Damage in Rats [Elektronische Daten] [Jerônimo Junqueira-Júnior, Ana Junqueira, Jand Medeiros, Sergio Barbosa, Ana Nogueira, José Mota, Ana Santana, Gerly Brito, Ronaldo Ribeiro, Roberto Lima-Júnior, Marcellus Souza] 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 180mg/kg, PO or SC). After 30min, the rats received absolute ethanol (5mlkg−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 (10mgkg−1, IP), glibenclamide (10mgkg−1, PO), or celecoxib (10mgkg−1, PO). After 30min, the animals were given amifostine (90mgkg−1, PO or SC), followed 30min later by gavage with absolute ethanol (5mlkg−1). Other rats were desensitized with capsaicin (125mgkg−1, SC) 8days 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. Springer Science+Business Media, LLC, 2010 Amifostine nationallicence Ethanol nationallicence Afferent sensory neurons nationallicence GSH nationallicence Gastric defense nationallicence Junqueira-Júnior Jerônimo 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, 60430-270, Fortaleza, CE, Brazil aut Junqueira Ana 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, 60430-270, Fortaleza, CE, Brazil aut Medeiros Jand 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, 60430-270, Fortaleza, CE, Brazil aut Barbosa Sergio 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, 60430-270, Fortaleza, CE, Brazil aut Nogueira Ana 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, 60430-270, Fortaleza, CE, Brazil aut Mota José 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, 60430-270, Fortaleza, CE, Brazil aut Santana Ana 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, 60430-270, Fortaleza, CE, Brazil aut Brito Gerly 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, 60430-270, Fortaleza, CE, Brazil aut Ribeiro Ronaldo 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, 60430-270, Fortaleza, CE, Brazil aut Lima-Júnior Roberto 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, 60430-270, Fortaleza, CE, Brazil aut Souza Marcellus 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, 60430-270, Fortaleza, CE, Brazil aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/2(2011-02-01), 314-322 0163-2116 56:2<314 2011 56 10620 https://doi.org/10.1007/s10620-010-1300-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-010-1300-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Junqueira-Júnior Jerônimo 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, 60430-270, Fortaleza, CE, Brazil aut NATIONALLICENCE 700 1- Junqueira Ana 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, 60430-270, Fortaleza, CE, Brazil aut NATIONALLICENCE 700 1- Medeiros Jand 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, 60430-270, Fortaleza, CE, Brazil aut NATIONALLICENCE 700 1- Barbosa Sergio 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, 60430-270, Fortaleza, CE, Brazil aut NATIONALLICENCE 700 1- Nogueira Ana 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, 60430-270, Fortaleza, CE, Brazil aut NATIONALLICENCE 700 1- Mota José 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, 60430-270, Fortaleza, CE, Brazil aut NATIONALLICENCE 700 1- Santana Ana 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, 60430-270, Fortaleza, CE, Brazil aut NATIONALLICENCE 700 1- Brito Gerly 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, 60430-270, Fortaleza, CE, Brazil aut NATIONALLICENCE 700 1- Ribeiro Ronaldo 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, 60430-270, Fortaleza, CE, Brazil aut NATIONALLICENCE 700 1- Lima-Júnior Roberto 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, 60430-270, Fortaleza, CE, Brazil aut NATIONALLICENCE 700 1- Souza Marcellus 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, 60430-270, Fortaleza, CE, Brazil aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/2(2011-02-01), 314-322 0163-2116 56:2<314 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer