title: Hydrogen sulfide prevents ethanol-induced gastric damage in mice: role of ATP-sensitive potassium channels and capsaicin-sensitive primary afferent neurons.
abstract: The aim of this study was to evaluate the protective effect of hydrogen sulfide (H(2)S) on ethanol-induced gastric lesions in mice and the influence of ATP-sensitive potassium (K(ATP)) channels, capsaicin-sensitive sensory afferent neurons, and transient receptor potential vanilloid (TRPV) 1 receptors on such an effect. Saline and L-cysteine alone or with propargylglycine, sodium hydrogen sulfide (NaHS), or Lawesson's reagent were administrated for testing purposes. For other experiments, mice were pretreated with glibenclamide, neurotoxic doses of capsaicin, or capsazepine. Afterward, mice received L-cysteine, NaHS, or Lawesson's reagent. After 30 min, 50% ethanol was administrated by gavage. After 1 h, mice were sacrificed, and gastric damage was evaluated by macroscopic and microscopic analyses. L-cysteine, NaHS, and Lawesson's reagent treatment prevented ethanol-induced macroscopic and microscopic gastric damage in a dose-dependent manner. Administration of propargylglycine, an inhibitor of endogenous H(2)S synthesis, reversed gastric protection induced by L-cysteine. Glibenclamide reversed L-cysteine, NaHS, or Lawesson's reagent gastroprotective effects against ethanol-induced macroscopic damage in a dose-dependent manner. Chemical ablation of sensory afferent neurons by capsaicin reversed gastroprotective effects of L-cysteine or H(2)S donors (NaHS or Lawesson's reagent) in ethanol-induced macroscopic gastric damage. Likewise, in the presence of the TRPV1 antagonist capsazepine, the gastroprotective effects of L-cysteine, NaHS, or Lawesson's reagent were also abolished. Our results suggest that H(2)S prevents ethanol-induced gastric damage. Although there are many mechanisms through which this effect can occur, our data support the hypothesis that the activation of K(ATP) channels and afferent neurons/TRPV1 receptors is of primary importance.
authors.affiliation: Department of Physiology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Jand Venes R
authors.initials: JV
authors.lastname: Medeiros
authors.forename: Víctor H
authors.initials: VH
authors.lastname: Bezerra
authors.forename: Antoniella S
authors.initials: AS
authors.lastname: Gomes
authors.forename: André Luiz R
authors.initials: AL
authors.lastname: Barbosa
authors.forename: Roberto César P
authors.initials: RC
authors.lastname: Lima-Júnior
authors.forename: Pedro Marcos G
authors.initials: PM
authors.lastname: Soares
authors.forename: Gerly Anne C
authors.initials: GA
authors.lastname: Brito
authors.forename: Ronaldo A
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: Marcellus H L P
authors.initials: MH
authors.lastname: Souza
mesh_terms: D000393:Air Pollutants / Q000494:pharmacology*; D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D003545:Cysteine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005753:Gastric Mucosa / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D054086:KATP Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009475:Neurons, Afferent / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology; D013272:Stomach Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D050916:TRPV Cation Channels / Q000502:physiology
chemical_list: D000393:Air Pollutants; D000480:Alkynes; D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D054086:KATP Channels; D020011:Protective Agents; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000431:Ethanol; D008315:Malondialdehyde; C009055:propargylglycine; D005978:Glutathione; D003545:Cysteine; D002211:Capsaicin; D005905:Glyburide; D005998:Glycine; D006862:Hydrogen Sulfide