Diminazene aceturate, an angiotensin-converting enzyme II activator, prevents gastric mucosal damage in mice: Role of the angiotensin-(1-7)/Mas receptor axis

Biochem Pharmacol. 2016 Jul 15:112:50-9. doi: 10.1016/j.bcp.2016.05.010. Epub 2016 May 27.

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.

Keywords: Anti-inflammatory; Antioxidant; Collagen; Gastroprotection; Healing.

MeSH terms

  • Acetic Acid / administration & dosage
  • Angiotensin I / metabolism*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Diminazene / analogs & derivatives*
  • Diminazene / pharmacology
  • Diminazene / therapeutic use
  • Disease Models, Animal
  • Ethanol / administration & dosage
  • Female
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Male
  • Mice
  • Peptide Fragments / metabolism*
  • Peptidyl-Dipeptidase A / metabolism*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / metabolism*
  • Receptors, G-Protein-Coupled / metabolism*
  • Renin-Angiotensin System / drug effects
  • Signal Transduction / drug effects*
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / metabolism
  • Stomach Ulcer / pathology
  • Stomach Ulcer / prevention & control

Substances

  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Ethanol
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)
  • diminazene aceturate
  • Acetic Acid
  • Diminazene