The cardioprotective effects of (-)-Epicatechin are mediated through arginase activity inhibition in a murine model of ischemia/reperfusion
| Autor: | Marcela Pacheco, Ivan Rubio-Gayosso, Aldo Moreno-Ulloa, Francisco Villarreal, Guillermo Ceballos, Lourdes Vega, Miguel Ortiz-Flores, Alicia Ortiz, Eduardo Meaney, Pilar Ortiz-Vilchis, Israel Ramirez-Sanchez, Nayelli Nájera |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cardiotonic Agents Protein Conformation Ischemia 030204 cardiovascular system & hematology Pharmacology Catechin Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo medicine Animals Enzyme Inhibitors Arginase biology Myocardium medicine.disease In vitro Molecular Docking Simulation Nitric oxide synthase Disease Models Animal 030104 developmental biology Biochemistry chemistry Reperfusion Injury biology.protein Phosphorylation Nitric Oxide Synthase Reperfusion injury |
| Zdroj: | European Journal of Pharmacology. 818:335-342 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2017.11.007 |
| Popis: | The production of nitric oxide (NO) by nitric oxide synthases (NOS) depends on the bioavailability of L-arginine as NOS competes with arginase for this common substrate. As arginase activity increases, less NO is produced and adverse cardiovascular consequences can emerge. (-)-Epicatechin (EPI), the most abundant flavonoid in cacao, has been reported to stimulate endothelial and neuronal NOS expression and function leading to enhanced vascular function and cardioprotective effects. However, little is known about the effects of EPI on myocardial arginase activity. The aim of the present study was to determine if EPI is able to interact and modulate myocardial arginase and NOS expression and activity. For this purpose, in silico modeling, in vitro activity assays and a rat model of ischemia/reperfusion injury were used. In silico and in vitro results demonstrate that EPI can interact with arginase and significantly decrease its activity. In vivo, 10 days of EPI pretreatment reduces ischemic myocardium arginase expression while increasing NOS expression and phosphorylation levels. Altogether, these results may partially account for the cardioprotective effects of EPI. |
| Databáze: | OpenAIRE |
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