Role of capsaicin-sensitive primary afferent neurons and non-protein sulphydryl groups on gastroprotective effect of amifostine against ethanol-induced gastric damage in rats.
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.
Junqueira-Júnior
Jerônimo
J
Brazilian Semi-Arid Institute of Biomedicine (INCT-IBISAB), Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
Junqueira
Ana Flávia Torquato Araújo
AF
Medeiros
Jand Venes R
JV
Barbosa
Sergio Henrique Brito
SH
Nogueira
Ana Carolina Pereira
AC
Mota
José Maurício Segundo Correia
JM
Santana
Ana Paula Macêdo
AP
Brito
Gerly Anne C
GA
Ribeiro
Ronaldo A
RA
Lima-Júnior
Roberto César P
RC
Souza
Marcellus H L P
MH
D004999:Amifostine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013272:Stomach Diseases / Q000139:chemically induced* / Q000517:prevention & control; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; D000431:Ethanol; D004999:Amifostine; D002211:Capsaicin