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Effects of oral N-acetylcysteine supplementation on walking capacity, vasodilatory capacity and oxidative stress markers in patients with peripheral arterial disease

Grant number: 13/05883-8
Support Opportunities:Regular Research Grants
Duration: July 01, 2013 - May 31, 2015
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Nelson Wolosker
Grantee:Nelson Wolosker
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Bruno Tesini Roseguini ; Cláudia Lúcia de Moraes Forjaz ; Edilamar Menezes de Oliveira ; Sang Won Han


Peripheral arterial disease is a common manifestation of atherosclerosis that is strongly associated with accelerated decline in functional capacity, decreased levels of daily physical activity and poor quality of life. A central mechanism in the pathophysiology of this disease is chronic increase in oxidative stress that contributes, among others, to dysfunction in vasodilatory capacity and consequently for the exercise intolerance characteristic of this condition. The main objective of this proposal is to test the hypothesis that oral supplementation with the antioxidant N-acetylcysteine (NAC) reduces oxidative stress and systemic inflammation, leading to improvement in exercise tolerance in patients with PAD. Specifically, we hypothesized that the administration of NAC favors the bioavailability of vasodilators such as nitric oxide and decrease the levels of inflammatory substances and vasoconstrictor agents, such as endothelin-1. Consequently, we expect that supplementation with this compound enhances vasodilation, resulting in increased muscle oxygenation during exercise and thus increasing the time of exercise tolerance in these patients. To test these hypotheses will be conducted a randomized, crossover, double-blind study in which twelve patients with PAD (ankle-brachial index <0.9) will be submitted after oral administration of NAC or placebo, to: 1) evaluation of vasodilatory capacity of the forearm and leg, and 2) a progressive exercise test on a treadmill. Blood samples will be collected before and after the exercise test for determination of plasma levels of oxidative stress markers (thiobarbituric acid reactive substances, 8-isoprostane, glutathione), inflammatory agents (TNF-a and IL-2), substances vasoactive (nitrite / nitrate and endothelin-1) and gene expression of microRNAs known to be related to the process of ischemia. The data will be compared by using t-test for repeated samples or the Wilcoxon test and by ANOVA for two factors for repeated samples, using P <0.05. (AU)

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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)
DA SILVA, JR., NATAN D.; ROSEGUINI, BRUNO T.; CHEHUEN, MARCEL; FERNANDES, TIAGO; MOTA, GLORIA F.; MARTIN, PRISCILA K. M.; HAN, SANG W.; FORJAZ, CLAUDIA L. M.; WOLOSKER, NELSON; DE OLIVEIRA, EDILAMAR M.. Effects of oral N-acetylcysteine on walking capacity, leg reactive hyperemia, and inflammatory and angiogenic mediators in patients with intermittent claudication. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 309, n. 5, p. H897-H905, . (13/05883-8)

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