Inhibition of endogenous hydrogen sulfide synthesis by PAG protects against ethanol-induced gastric damage in the rat.
Hydrogen sulfide (H(2)S) is a gaseous mediator involved in a multitude of physiological functions; however the role of H(2)S 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(2)S synthesis, on ethanol-induced gastric injury in rat and to examine the role of l-cysteine, exogenous H(2)S, prostaglandins, non-protein sulphydryls groups, nitric oxide and K(ATP) channels in the gastroprotective effect of PAG. Administration of PAG (3.12 to 75mg/kg i.p.) or l-cysteine (0.3 to 300mg/kg, p.o.) exhibited a dose-dependent protective effect after intragastric administration of 1ml of ethanol to induce gastric injury. The gastroprotective effect of PAG (25mg/kg i.p.) was maintained after post-treatment with l-cysteine (10mg/kg p.o.), while NaHS (8.4mg/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 (10mg/kg i.p.) and N-ethylmaleimide (NEM, 10mg/kg s.c.) resulted in a reversion of the gastroprotective effect of PAG while N(G)-nitro-l-arginine methyl ester (L-NAME, 70mg/kg s.c.), glibenclamide (1mg/kg i.p.) or diazoxide (3mg/kg i.p.) did not induce any changes. These results suggest that ethanol-induced gastric injury is related with an increment of endogenous H(2)S levels, and therefore a decrement of H(2)S levels by PAG is a benefit to protect gastric injury caused by ethanol.
Chávez-Piña
Aracely Evangelina
AE
Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, México.
Tapia-Alvarez
Gabriela Rubí
GR
Navarrete
Andrés
A
D000480:Alkynes / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000480:Alkynes; D000897:Anti-Ulcer Agents; D000431:Ethanol; C009055:propargylglycine; D005998:Glycine; D006862:Hydrogen Sulfide