title: Diminazene aceturate, an angiotensin-converting enzyme II activator, prevents gastric mucosal damage in mice: Role of the angiotensin-(1-7)/Mas receptor axis.
abstract: The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects in various organisms, including gastroprotection. ACE II is responsible for converting Ang II into an active peptide, Ang-(1-7), which in turn binds the Mas receptor. Recent studies have shown that diminazene aceturate (Dize) a trypanocidal used in animals, activates ACE II. Thus, in this study, we aimed to evaluate the gastroprotective effects of Dize via the ACE II/Ang-(1-7)/Mas receptor pathway against gastric lesions induced by ethanol and acetic acid in mice. The results showed that Dize could promote gastric protection via several mechanisms, including increased levels of antioxidants and anti-inflammatory factors (e.g., decreasing tumor necrosis factor and interleukin-6 expression and reducing myeloperoxidase activity), maturation of collagen fibers, and promotion of re-epithelialization and regeneration of gastric tissue in different injury models. Thus, Dize represents a novel potential gastroprotective agent.
authors.affiliation: Postgraduate Program in Biomedical Sciences, Federal University of Piauí, Parnaíba, Piauí, Brazil.
authors.forename: Luan Kelves M
authors.initials: LK
authors.lastname: Souza
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: Biotechnology and Biodiversity Center Research, BIOTEC, 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: Thiago S L
authors.initials: TS
authors.lastname: Araújo
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: Medicinal Plant Research Center, NPPM, Postgraduate Program in Pharmacology, Federal University of Piauí, Teresina, Piauí, Brazil.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Costa
authors.affiliation: Medicinal Plant Research Center, NPPM, Postgraduate Program in Pharmacology, Federal University of Piauí, Teresina, Piauí, Brazil.
authors.forename: Fabiana M
authors.initials: FM
authors.lastname: Souza
authors.affiliation: Postgraduate Program in Morphofunctional Sciences, Department of Morphology, Faculty of Medicine, Federal University Ceará, Fortaleza-CE, Brazil.
authors.forename: Dvison M
authors.initials: DM
authors.lastname: Pacífico
authors.affiliation: Postgraduate Program in Morphofunctional Sciences, Department of Morphology, Faculty of Medicine, Federal University Ceará, Fortaleza-CE, Brazil.
authors.forename: Conceição S
authors.initials: CS
authors.lastname: Martins
authors.affiliation: Department of Physiology and Pharmacology, Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Federal University of Ceará, Fortaleza-CE, Brazil.
authors.forename: Renan O
authors.initials: RO
authors.lastname: Silva
authors.affiliation: Department of Physiology and Pharmacology, Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Federal University of Ceará, Fortaleza-CE, Brazil.
authors.forename: Marcellus H L P
authors.initials: MH
authors.lastname: Souza
authors.affiliation: Postgraduate Program in Biomedical Sciences, Federal University of Piauí, Parnaíba, Piauí, Brazil.
authors.forename: Gilberto S
authors.initials: GS
authors.lastname: Cerqueira
authors.affiliation: Postgraduate Program in Biomedical Sciences, Federal University of Piauí, Parnaíba, Piauí, Brazil; Biotechnology and Biodiversity Center Research, BIOTEC, Postgraduate Program in Biotechnology, Federal University of Piauí, Parnaíba, Piauí, Brazil; Medicinal Plant Research Center, NPPM, Postgraduate Program in Pharmacology, Federal University of Piauí, Teresina, Piauí, Brazil. Electronic address: jandvenes@ufpi.edu.br.
authors.forename: Jand Venes R
authors.initials: JV
authors.lastname: Medeiros
mesh_terms: D019342:Acetic Acid / Q000008:administration & dosage; D000803:Angiotensin I / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D004133:Diminazene / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control
chemical_list: D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000431:Ethanol; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7); C003915:diminazene aceturate; D019342:Acetic Acid; D004133:Diminazene
keywords: Anti-inflammatory; Antioxidant; Collagen; Gastroprotection; Healing