title: Evidence that d-cysteine protects mice from gastric damage via hydrogen sulfide produced by d-amino acid oxidase.
abstract: Hydrogen sulfide (H2S) is a signaling molecule in the gastrointestinal tract. H2S production can derive from d-cysteine via various pathways, thus pointing to a new therapeutic approach: delivery of H2S to specific tissues. This study was designed to evaluate the concentration and effects of H2S (generated by d-amino acid oxidase [DAO] from d-cysteine) in the gastric mucosa and the protective effects against ethanol-induced lesions in mice. Mice were treated with l-cysteine or d-cysteine (100 mg/kg per os). Other groups received oral l-propargylglycine (cystathionine γ-lyase inhibitor, 100 mg/kg) or indole-2-carboxylate (DAO inhibitor), and 30 min later, received d- or l-cysteine. After 30 min, 50% ethanol (2.5 mL/kg, per os) was administered. After 1 h, the mice were euthanized and their stomachs excised and analyzed. Pretreatment with either l-cysteine or d-cysteine significantly reduced ethanol-induced lesions. Pretreatment of d-cysteine- or l-cysteine-treated groups with indole-2-carboxylate reversed the gastroprotective effects of d-cysteine but not l-cysteine. Histological analysis revealed that pretreatment with d-cysteine decreased hemorrhagic damage, edema, and the loss of the epithelium, whereas the administration of indole-2-carboxylate reversed these effects. d-Cysteine also reduced malondialdehyde levels but maintained the levels of reduced glutathione. Furthermore, pretreatment with d-cysteine increased the synthesis of H2S. Thus, an H2S-generating pathway (involving d-cysteine and DAO) is present in the gastric mucosa and protects this tissue from ethanol-induced damage by decreasing direct oxidative damage.
authors.affiliation: Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Parnaíba, Piauí, Brazil; Biotechnology and Biodiversity Center Research, BIOTEC, Postgraduate Program in Biotechnology, Federal University of Piauí, Parnaíba, Piauí, Brazil.
authors.forename: Luan Kelves M
authors.initials: LK
authors.lastname: Souza
authors.affiliation: Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Parnaíba, Piauí, Brazil; Biotechnology and Biodiversity Center Research, BIOTEC, Postgraduate Program in Biotechnology, Federal University of Piauí, Parnaíba, Piauí, Brazil.
authors.forename: Thiago S L
authors.initials: TS
authors.lastname: Araújo
authors.affiliation: Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Parnaíba, Piauí, Brazil.
authors.forename: Nayara A
authors.initials: NA
authors.lastname: Sousa
authors.affiliation: Biotechnology and Biodiversity Center Research, BIOTEC, Postgraduate Program in Biotechnology, Federal University of Piauí, Parnaíba, Piauí, Brazil.
authors.forename: Francisca Beatriz M
authors.initials: FB
authors.lastname: Sousa
authors.affiliation: Biotechnology and Biodiversity Center Research, BIOTEC, Postgraduate Program in Biotechnology, Federal University of Piauí, Parnaíba, Piauí, Brazil.
authors.forename: Kerolayne M
authors.initials: KM
authors.lastname: Nogueira
authors.affiliation: Department of Physiology and Pharmacology, Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Lucas A D
authors.initials: LA
authors.lastname: Nicolau
authors.affiliation: Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Parnaíba, Piauí, Brazil; Biotechnology and Biodiversity Center Research, BIOTEC, Postgraduate Program in Biotechnology, Federal University of Piauí, Parnaíba, Piauí, Brazil. Electronic address: jandvenes@ufpi.edu.br.
authors.forename: Jand Venes R
authors.initials: JV
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology*; D003605:D-Amino-Acid Oxidase / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D013272:Stomach Diseases / Q000139:chemically induced / Q000378:metabolism
chemical_list: D000975:Antioxidants; D000431:Ethanol; D008315:Malondialdehyde; C485958:Dao1 protein, mouse; D003605:D-Amino-Acid Oxidase; D005978:Glutathione; D003545:Cysteine; D006862:Hydrogen Sulfide
keywords: Antioxidant; Gastric injury; Hydrogen sulfide; d-amino acid oxidase; d-cysteine