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

Hydrogen Sulfide (H2S) is a gaseous mediator involved in a multitude of physiological functions, however the role of H2S in the gut 15 far from being understood completely The aim of this Study was to determine the effect of D-L-propargylglycine (PAG). an inhibitor of H2S synthesis, on ethanol-induced gastric injury in rat and to examine the role of L-cysteine. exogenous H2S, 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 PAIS (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 H2S levels, and therefore a decrement of H2S levels by PAG is a benefit to protect gastric injury caused by ethanol (C) 2009 Elsevier B.V. All rights reserved