Anti-diarrheal therapeutic potential of diminazene aceturate stimulation of the ACE II/Ang-(1-7)/Mas receptor axis in mice: A trial study
| Autor: | Thiago M. Sales, Thiago S.L. Araújo, Karine Lima Silva, Marcellus H.L.P. Souza, Kerolayne M. Nogueira, Talita Magalhães Rocha, Nayara A. Sousa, Ana Patrícia de Oliveira, Francisca Beatriz M. Sousa, Luan Kelves Miranda de Souza, Pedro Jorge Caldas Magalhães, Luzia Kalyne Almeida Moreira Leal, Jand V.R. Medeiros |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Diarrhea Male Castor Oil Stimulation Inflammation Pharmacology Biochemistry Proto-Oncogene Mas Proinflammatory cytokine Receptors G-Protein-Coupled Renin-Angiotensin System 03 medical and health sciences Mice 0302 clinical medicine Proto-Oncogene Proteins Renin–angiotensin system Medicine Animals Receptor Antidiarrheals chemistry.chemical_classification Gastrointestinal tract Dose-Response Relationship Drug business.industry Angiotensin II Peptide Fragments Gastrointestinal Tract 030104 developmental biology Enzyme Metabotropic receptor chemistry 030220 oncology & carcinogenesis medicine.symptom Angiotensin I business Diminazene |
| Zdroj: | Biochemical pharmacology. 186 |
| ISSN: | 1873-2968 |
| Popis: | The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects on the body, especially on the cardiac system and gastrointestinal tract. ACE II is responsible for converting Ang II into the active peptide Ang-(1-7), which in turn binds to a metabotropic receptor, the Mas receptor (MasR). Recent studies have demonstrated that Diminazene Aceturate (DIZE), a trypanosomicide used in animals, activates the ACE II pathway. In this study, we aimed to evaluate the antidiarrheal effects promoted by the administration of DIZE to activate the ACE II/Ang-(1-7)/MasR axis in induced diarrhea mice models. The results show that activation of the ACE II pathway exerts antidiarrheal effects that reduce total diarrheal stools and enteropooling. In addition, it increases Na+/K+-ATPase activity and reduces gastrointestinal transit and thus inhibits contractions of intestinal smooth muscle; decreases transepithelial electrical resistance, epithelial permeability, PGE2-induced diarrhea, and proinflammatory cytokines; and increases anti-inflammatory cytokines. Enzyme-linked immunosorbent assay (ELISA) demonstrated that DIZE, when activating the ACE II/Ang-(1-7)/MasR axis, can still interact with GM1 receptors, which reduces cholera toxin-induced diarrhea. Therefore, activation of the ACE II/Ang-(1-7)/MasR axis can be an important pharmacological target for the treatment of diarrheal diseases. |
| Databáze: | OpenAIRE |
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