Involvement of endogenous nitric oxide and sulfhydryl compounds in ebrotidine-induced gastroprotection.
The role of endogenous nitric oxide and sulfhydryl compounds in the prevention by ebrotidine (N-[(E)- [[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl]amino] methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) (100 mg/kg i.g.) of ethanol-induced gastric damage in rats was demonstrated. When the animals were pretreated with N-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, at the dose of 10 mg/kg i.v., the mucosal lesions were aggravated and the gastroprotective action of ebrotidine decreased from 85% to 24%. This decrease in ebrotidine protection was antagonized by L-arginine (200 mg/kg i.v.), the lesion inhibition rate being 69%. D-arginine (200 mg/kg i.v.) was ineffective and the inhibition afforded by ebrotidine was only 14%. Pretreatment with N-ethylmaleimide, a sulfhydryl blocker, at the dose of 50 mg/kg s.c., increased the mucosal lesion induced by ethanol, and the gastroprotective action of ebrotidine decreased from 75% to 9%. These results suggest that endogenous nitric oxide and sulfhydryl compounds play a crucial role in the gastroprotective activity of ebrotidine.
Palop
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D
Centro de Investigación Farmacéutica Grupo Ferrer, Barcelona, Spain.
Conejo
L
L
Sacristán
A
A
Ortiz
J A
JA
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001557:Benzenesulfonates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects; D005033:Ethylmaleimide / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010437:Peptic Ulcer / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013438:Sulfhydryl Compounds / Q000502:physiology*; D013844:Thiazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001557:Benzenesulfonates; D006635:Histamine H2 Antagonists; D013438:Sulfhydryl Compounds; D013844:Thiazoles; D009569:Nitric Oxide; D000431:Ethanol; D001120:Arginine; D005033:Ethylmaleimide; C075156:ebrotidine; D019331:NG-Nitroarginine Methyl Ester