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Effects of luteolin on the endothelial generation of reactive oxygen species induced by Angiotensin II.


The endothelial cell integrates mechanical and biochemical signals capable of stimulating the production of nitric oxide (NO) and superoxide anion (O2*¯). O2*¯ reacts directly with NO, reducing its bioavailability and generating peroxynitrite (ONOO-). In the vasculature the O2*¯ levels are determined mainly by the activity of the enzyme NAD(P) H oxidase and its metabolism in H2O2 by the enzyme superoxide dismutase (SOD). It is assumed that the interactions and the balance between these endothelial mediators are fundamental for the maintenance of several vascular functions, such as regulation of blood flow and blood pressure. Angiotensin II (Ang II) is a potent oxidative stress inducing agent in vascular cells via activation of the enzyme NAD(P)H oxidase. This mechanism is well described in the vascular smooth muscle, but little elucidated in the endothelium. Luteolin is a flavonoid with antioxidant properties, and recent studies have indicated its ability to prevent some of the pro-oxidant actions induced by Ang II in cardiovascular tissues. The present project aims to evaluate the endothelial effects of luteolin per se, and its possible interference with the pro-oxidant actions of Ang II at the endothelium. For this, immortalized cultures of rat vena cava endothelium will be incubated with Ang II and / or luteolin, followed by analysis of the production of the reactive species NO, O2*¯ and the ONOO- and H2O2 metabolites, using specific fluorescent probes. The biochemical pathways involved in the generation or degradation of these molecules will be evaluated by determining the protein density and / or activity of the corresponding enzymes. Further, other parameters will be addressed by the investigation of end products of these reactive species in the endothelial cell. Thus, the present proposal aims at an overall evaluation of the effects of Ang II and luteolin, separately and in association, on the various pathways involved in the balance of pro-and anti-oxidant endothelial agents. (AU)

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(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)
REIS ASSUNCAO, HENRIQUE CHARLANTI; COELHO CRUZ, YAN MILEN; BERTOLINO, JESSICA SILVA; TAMBORELLI GARCIA, RAPHAEL CAIO; FERNANDES, LILIAM. Protective effects of luteolin on the venous endothelium. Molecular and Cellular Biochemistry, v. 476, n. 4, . (17/22028-5, 17/21834-8)

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