Envelhecimento: avaliação da capacidade antioxidante e anti-inflamatória do Resveratrol através do estudo das vias de sinalização celular PKA, MAPK E AKT/PKB em células mononucleares humanas in vitro

Abstract

Aging is characterized by a slow and progressive process in which various morphological, functional and biochemical changes occur which contribute to the increased vulnerability and incidence of pathological processes in the organism such as diabetes, cardiovascular disorders, Alzheimer's disease and other morbidities. These changes can be generated through "Oxidative Stress", which is marked by imbalance in the redox state, due to the exacerbation of the pro-oxidants or dysfunction of the antioxidant mechanisms. This imbalance is closely associated with immunosenescence, in which the elderly individual presents functional reduction of the innate immune system, increased basal inflammatory activity and elevated expression of proinflammatory cytokines that provide a state of chronic inflammation called Inflammaging. In counterpoint, there are the antioxidant compounds, produced in an endogenous or exogenous way in order to block and / or eliminate such oxidant species, preventing the oxidation of biomolecules. As part of the exogenous antioxidant substances classified as non-enzymatic, Resveratrol (RSV) is a polyphenol that has several proven biological activities as antioxidant, anti-inflammatory and anti-tumor capacity. The objective of our study was to verify the possible antioxidant and/or anti-inflammatory effect of Resveratrol in an environment of oxidative stress in Human Mononuclear Cells (PBMC) of donors aged 40-59 and 60-80 years. For that, 5 ìM of Resveratrol and a stimulus with 0.64% v/v H2O2 were used, in which through the luminol-dependent chemiluminescence assay there was a higher performance of RSV in the middle age group, a profile also found in dosages of IL-6, TNF and IL- 10. This profile related to the effect of RSV on the middle age group was also found in relation to the concentration of lipoprotein A and Fosfolipase A2 heart biomarkers in an in vivo interventional study. When interfering with the compound in the signaling pathways PKA, Akt/PKB and MAPK, only the third pathway promoted the regulation of RSV activity in the experiments. Through the nitric oxide production test, RSV did not promote significant alteration in both age groups studied. We observed in this study that RSV presents a better anti-inflammatory and anti-inflammatory activity in a preventive way in human PBMC and its performance is altered in aging by changing the signaling pattern of the MAPK pathway