Pharmacological characterization of the effects induced by ruthenium complex cis-[Ru(H-dcbpy-)2(Cl)(NO2-)] in endothelial dysfunction cells

• Grant number: 14/02250-7
• Support type: Scholarships in Brazil - Master
• Effective date (Start): July 01, 2014
• Effective date (End): February 29, 2016
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Gerson Jhonatan Rodrigues
• Grantee: Tereza Cristina Buzinari
• Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 12/24477-8 - Utilization of ruthenium complex as pharmacological strategy to revert and/or prevent the endothelial dysfunction, AP.JP

Abstract

Endothelial dysfunction is characterized mainly by decreasing the ability of endothelial cells to release nitric oxide (NO). There is evidence that reduction in bioavailability of NO contribute to development and progression of atherosclerosis and hypertension, which may lead to the development of ischemic heart disease, myocardial infarction, and even heart failure. One of the factors contributing to endothelial dysfunction is the presence of high intracellular levels of superoxide (O2-), which reacts with NO and form peroxynitrite (ONOO-), lowering NO levels. The ruthenium complexes have been studied as NO donors, which are very attractive because of their low toxicity and be active in their stable forms under physiological conditions. In previous studies it was shown that the cis-[Ru(H-dcbpy-)2(Cl)(NO2-)] generates NO in rat artery and is able to inactivate the O2- formed in the extracellular medium. Thus, our hypothesis is that this compound can inactivate O2- formed intracellularly and increase NO levels. To test this hypothesis, it will be used endothelial cell culture stimulated with angiotensin II, where it will be possible to obtain dysfunctional endothelial cells with high concentrations of intracellular O2-. This study will allow evaluate the pharmacological effect of the cis-[Ru(H-dcbpy-)2(Cl)(NO2-)] compound to reverse and/or prevent endothelial dysfunction and pharmacological characterization of dependent effects of removal of O2- and induced release of NO by this drug.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BUZINARI, TEREZA CRISTINA; OISHI, JORGE CAMARGO; DE MORAES, THIAGO FRANCISCO; VATANABE, IZABELA PEREIRA; SELISTRE-DE-ARAUJO, HELOISA SOBREIRO; PESTANA, CEZAR RANGEL; RODRIGUES, GERSON JHONATAN. Treatment with sodium nitroprusside improves the endothelial function in aortic rings with endothelial dysfunction. European Journal of Pharmaceutical Sciences, v. 105, p. 144-149, JUL 15 2017. Web of Science Citations: 2.