Published in:
01-02-2011 | Original Article
Role of Capsaicin-Sensitive Primary Afferent Neurons and Non-protein Sulphydryl Groups on Gastroprotective Effect of Amifostine Against Ethanol-Induced Gastric Damage in Rats
Published in: Digestive Diseases and Sciences | Issue 2/2011
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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.