A via L-arginina-óxido nítrico e o estresse oxidativo associados às alterações imunológicas, inflamatórias e aterotrombóticas na depressão

• Autor(a) principal: Carmo, Monique Bezerra Oliveira Ormonde do
• Data de Publicação: 2016
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/7792
• topic: Major Depression; Neutrophils; Nitric oxide; Oxidative stress; Depressão Maior; Neutrófilos; Óxido nítrico; Estresse oxidativo; Depressão mental; Óxido nítrico; Transtorno depressivo maior; Estresse oxidativo; CNPQ::CIENCIAS DA SAUDE

Major depressive disorder (MDD) is a common, severe and disabling mental disorder, with an increasing prevalence worldwide. In addition to the increased risk of death due to suicide, depressive symptoms are also associated with an increased risk of cardiovascular morbidity and mortality. Additionally, MDD can be considered an independent risk factor for cardiovascular diseases. One of the most important mediators in this relationship is nitric oxide (NO), a molecule synthesized not only by the endothelium but also by figurative blood elements such as neutrophils, platelets and erythrocytes. NO plays a key role in vasodilation, generation of reactive oxygen species, in addition to platelets activation, adhesion and aggregation, and cytotoxic activity of the immune system. Thus, the aim of this study was to investigate the L-arginine-nitric oxide pathway and oxidative stress markers in erythrocytes and neutrophils, as well as to analyze the action of these in the platelet aggregation of MDD patients. L-arginine influx, NO synthase activity and cGMP levels were measured in neutrophils and erythrocytes from 14 untreated (12 F, 2 M) MDD patients and 15 healthy (11 F, 4 M) controls (HC). In addition, the expression of the enzymes iNOS, eNOS and gp91phox NADPH oxidase, the oxidative burst and the amino acid levels in neutrophils, and their effects on platelet aggregation were evaluated. The osmotic fragility, the proteins carbonylation and the antioxidant activity SOD, GPx and catalase enzymes in MDD and controls erythrocytes were also assessed. There was no difference in L-arginine transport in both cells, but NOS activity and cGMP levels were reduced in MDD compared to HC neutrophils. On the other hand, eNOS and iNOS were overexpressed in MDD neutrophils. NADPH oxidase gp91phox expression and oxidative burst did not differ in neutrophils between groups. MDD patients showed an increase in platelet aggregation compared to HC. After neutrophils incubation, a platelet aggregation reduction was observed in both groups. No difference was observed in osmotic fragility, proteins carbonylation, and catalase enzyme activity, but SOD and GPx activity were decreased in erythrocytes in MDD. Based on these results, there could be an oxidative stress increase in MDD due to the low availability of NO in neutrophils, and the decreased antioxidant defenses in erythrocytes. Another important finding was that the neutrophils presence reduced platelet aggregation, suggesting that NO produced by these cells is sufficient to act on platelets as well as on adjacent cells. Finally, a better understanding of the low NO bioavailability in the phagocytic neutrophil function and its interaction with other cells and tissues would help to clarify the mechanisms associated with immune system dysfunction and increased cardiovascular morbidity in MDD.