Role of Capsaicin-Sensitive Primary Afferent Neurons and Non-protein Sulphydryl Groups on Gastroprotective Effect of Amifostine Against Ethanol-Induced Gastric Damage in Rats
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Jeroˆnimo Junqueira-Ju´nior Ana Fla´via Torquato Arau´ jo Junqueira Jand Venes R. Medeiros Sergio Henrique Brito Barbosa Ana Carolina Pereira
- چاپ و سال / کشور: 2010
Description
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, nonprotein 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 administrationPOandSC 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.
Dig Dis Sci (2011) 56:314–322 DOI 10.1007/s10620-010-1300-8 Received: 28 October 2009 / Accepted: 3 June 2010 / Published online: 16 June 2010
