Inhibition of endogenous hydrogen sulfide synthesis by PAG protects against ethanol-induced gastric damage in the rat

• Published in: European journal of pharmacology 2010-03, Vol.630 (1), p.131-136
• Main Authors: Chávez-Piña, Aracely Evangelina, Tapia-Álvarez, Gabriela Rubí, Navarrete, Andrés
• Format: Article
• Language: English
• Subjects: Alkynes - pharmacology; Animals; Anti-Ulcer Agents - pharmacology; Biological and medical sciences; Dose-Response Relationship, Drug; Ethanol; Ethanol - pharmacology; Gastric injury; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; Glycine - analogs & derivatives; Glycine - pharmacology; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Male; Medical sciences; PAG; Pharmacology. Drug treatments; Potassium channel ATP-sensitive; Rats; Rats, Wistar; Stomach - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2009.12.017

Hydrogen sulfide (H 2S) is a gaseous mediator involved in a multitude of physiological functions; however the role of H 2S in the gut is far from being understood completely. The aim of this study was to determine the effect of d- l-propargylglycine (PAG), an inhibitor of H 2S synthesis, on ethanol-induced gastric injury in rat and to examine the role of l-cysteine, exogenous H 2S, prostaglandins, non-protein sulphydryls groups, nitric oxide and K ATP channels in the gastroprotective effect of PAG. Administration of PAG (3.12 to 75 mg/kg i.p.) or l-cysteine (0.3 to 300 mg/kg, p.o.) exhibited a dose-dependent protective effect after intragastric administration of 1 ml of ethanol to induce gastric injury. The gastroprotective effect of PAG (25 mg/kg i.p.) was maintained after post-treatment with l-cysteine (10 mg/kg p.o.), while NaHS (8.4 mg/kg p.o.) inhibited this effect. The levels of gastric hydrogen sulfide were increased after ethanol-induced gastric damage and they were reverted by PAG while prostaglandin E 2 levels in gastric tissue were decreased by ethanol and PAG did not revert to this effect. Pretreatment with indomethacin (10 mg/kg i.p.) and N-ethylmaleimide (NEM, 10 mg/kg s.c.) resulted in a reversion of the gastroprotective effect of PAG while N G-nitro- l-arginine methyl ester (L-NAME, 70 mg/kg s.c.), glibenclamide (1 mg/kg i.p.) or diazoxide (3 mg/kg i.p.) did not induce any changes. These results suggest that ethanol-induced gastric injury is related with an increment of endogenous H 2S levels, and therefore a decrement of H 2S levels by PAG is a benefit to protect gastric injury caused by ethanol.