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Evidence that d-cysteine protects mice from gastric damage via hydrogen sulfide produced by d-amino acid oxidase

Hydrogen sulfide (H S) is a signaling molecule in the gastrointestinal tract. H S production can derive from d-cysteine via various pathways, thus pointing to a new therapeutic approach: delivery of H S to specific tissues. This study was designed to evaluate the concentration and effects of H S (ge...

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Bibliographic Details
Published in:Nitric oxide 2017-04, Vol.64, p.1-6
Main Authors: Souza, Luan Kelves M, Araújo, Thiago S L, Sousa, Nayara A, Sousa, Francisca Beatriz M, Nogueira, Kerolayne M, Nicolau, Lucas A D, Medeiros, Jand Venes R
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Language:English
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Summary:Hydrogen sulfide (H S) is a signaling molecule in the gastrointestinal tract. H S production can derive from d-cysteine via various pathways, thus pointing to a new therapeutic approach: delivery of H S to specific tissues. This study was designed to evaluate the concentration and effects of H S (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 H S. Thus, an H S-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.
ISSN:1089-8603
1089-8611
DOI:10.1016/j.niox.2017.01.010