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Utilization of ruthenium complex as pharmacological strategy to revert and/or prevent the endothelial dysfunction

Grant number: 12/24477-8
Support type:Research Grants - Young Investigators Grants
Duration: April 01, 2013 - March 31, 2017
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal Investigator:Gerson Jhonatan Rodrigues
Grantee:Gerson Jhonatan Rodrigues
Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
Assoc. researchers:Lusiane Maria Bendhack ; Roberto Santana da Silva
Associated scholarship(s):14/02231-2 - Use of ruthenium complex cis-[Ru (bpy) 2 (NO2) (no)] (PF6) 2) to reverse and / or prevent endothelial dysfunction in arterial hypertension, BP.MS
14/02250-7 - Pharmacological characterization of the effects induced by ruthenium complex cis-[Ru(H-dcbpy-)2(Cl)(NO2-)] in endothelial dysfunction cells, BP.MS

Abstract

The endothelial dysfunction has been considered as an indicator of cardiovascular diseases, considering that low nitric oxide (NO) bioavailability contributes to development and progression of hypertension and atherosclerosis, which can induces cardiac and cerebral ischemic diseases. The endothelial dysfunction is mainly characterized by decrease on capacity of endothelial cells to release NO. The NO has a couple of beneficial physiologic effects, including: modulation of vascular tonus, inhibition of platelet aggregation, decreases the expression of adhesion molecule, decreases vascular smooth muscle cells proliferation and induces a anti-inflammatory effect by PPARg activation and NF-kB inhibition. The NO is a radical specie and reacts rapidly with other molecules that have unpaired electron, being extremely unstable under physiological conditions. The superoxide anion (O2-) decreases the NO bioavailability and activates NF-ºB, an important pro-inflammatory transcription factor, which has been found activated in cells from cardiovascular system in the presence of cardiovascular diseases, including: hypertension, atherosclerosis and heart failure. Thus, the decrease of NF-ºB activity induced by NO and by O2- scavenging can be a good strategy on prevention and/or reversion of cardiovascular diseases. In previous studies we have verified that the ruthenium complex cis-[Ru(H-dcbpy-)2(Cl)(NO)] and cis-[Ru(bpy)2(NO2-)(NO)](PF6)2 actuate as a NO donors and the compound cis-[Ru(H-dcbpy-)2(Cl)(NO)] inactivate the O2- generated by xantine oxidase. This way, our hypothesis is that these compounds can revert and/or prevent the endothelial dysfunction. This effect could normalize the blood pressure, decrease the risk of development of cardiac and cerebral ischemic diseases and heart failure. To test our hypothesis, the hypertension animal model two kidney one clip (2K-1C) and endothelium cells in culture stimulated with angiotensin II will be used, considering that in these conditions will be possible to get dysfunctional endothelial cell with high O2- concentration. The principal aim of this study will be to test our hypothesis and proceed the pharmacological characterization of dependent effects of O2- scavenging and NO release induced by these ruthenium compounds. This project will allow the implantation of an emergent research area on Centro de Ciências Biológicas e da Saúde (CCBS), from Departamento de Ciências Fisiológicas (DCF). The DCF shows a good structure on Cellular Biology, Biochemistry and Endocrinology, which will be available for the development of this project through established collaborations with teachers of this department. Also, this project will have the collaboration of Profa. Dr. Lusiane M. Bendhack and Prof. Dr Roberto S. Da Silva, both from Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP. (AU)

Scientific publications (6)
(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)
MARTINELLI, ARIANE MIGLIATO; DOS SANTOS RODRIGUES, CARLA NASCIMENTO; DE MORAES, THIAGO FRANCISCO; RODRIGUES, GERSON JHONATAN. In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation. JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES, v. 21, p. 38-45, 2018. Web of Science Citations: 1.
VATANABE, IZABELA PEREIRA; DOS SANTOS RODRIGUES, CARLA NASCIMENTO; BUZINARI, TEREZA CRISTINA; DE MORAES, THIAGO FRANCISCO; DA SILVA, ROBERTO SANTANA; RODRIGUES, GERSON JHONATAN. Ruthenium Complex Improves the Endothelial Function in Aortic Rings From Hypertensive Rats. Arquivos Brasileiros de Cardiologia, v. 109, n. 2, p. 124-131, AUG 2017. Web of Science Citations: 1.
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.
OISHI, J. C.; DE MORAES, T. F.; BUZINARI, T. C.; CARNIO, E. C.; PARIZOTTO, N. A.; RODRIGUES, G. J. Hypotensive acute effect of photobiomodulation therapy on hypertensive rats. Life Sciences, v. 178, p. 56-60, JUN 1 2017. Web of Science Citations: 3.
VICTOR FABRICIO; JORGE CAMARGO OISHI; BRUNA GABRIELE BIFFE; LEANDRO DIAS GONÇALVES RUFFONI; KARINA ANA DA SILVA; KEICO OKINO NONAKA; GERSON JHONATAN RODRIGUES. Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats. Arquivos Brasileiros de Cardiologia, v. 108, n. 2, p. 116-121, Fev. 2017. Web of Science Citations: 5.
PESTANA, CEZAR RANGEL; OISHI, JORGE CAMARGO; SALISTRE-ARAUJO, HELOISA SOBREIRO; RODRIGUES, GERSON JHONATAN. Inhibition of Autophagy by Chloroquine Stimulates Nitric Oxide Production and Protects Endothelial Function during Serum Deprivation. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v. 37, n. 3, p. 1168-1177, SEP 2015. Web of Science Citations: 11.

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