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 is 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 KATP 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 E2 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 NG-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.