RESUMO
Currently, the important role of oxidative stress in the aging process and in neurodegenerative diseases has been highlighted, suggesting the beneficial effect of antioxidants as adjuvant therapy. Resveratrol (RSV) is a polyphenolic compound used in the clinic and has been shown as an antioxidant and anti-inflammatory. Therefore, the objective was to verify neuroprotective and modulating effects of RSV on N2-A cells, pre or post inserted into an oxidative stress environment. For this, two treatment conditions were established: pre-stimulus and post-stimulus. The analysis of AMPK and SIRT1 cell signaling pathways was performed through the chemiluminescence assay using the dorsomorphin and EX527 inhibitors, respectively. The inflammatory profile was also evaluated in these neural cells, through the levels of IL-6, TNF, and IL-10. We observed that RSV in N2-A cells has anti-inflammatory effect and antioxidant property and it mechanism is dependent on the SIRT1 signaling pathway. RSV effects occurs most markedly when cells have been pre-stimulated before inducing an oxidative stress environment. These results are important for conducting more adequate protocols in the medical and nutritional clinic.
Assuntos
Antioxidantes , Sirtuína 1 , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Resveratrol/farmacologia , Estresse Oxidativo , Anti-Inflamatórios/farmacologiaRESUMO
One of the causes for aging is free radical damage. Resveratrol (RSV), a polyphenolic compound has been shown to act as an antioxidant and anti-inflammatory. The objective this study was to verify in an oxidative stress environment in Human Mononuclear cells from Middle aged and Elderly donors, the existence of a change in the SIRT1 and AMPK signaling pattern by RSV. In both age groups there was a reduction in reactive oxygen species (ROS) in cells stimulated with RSV. It was observed that in the Elderly group there was a higher production of ROS and that the reduction from RSV was smaller compared to the other group. There was an increased activity of Superoxide Dismutase in cells exposed to RSV in the elderly group. It was observed that for the Middle Aged group, SIRT 1 and AMPK are antioxidant pathways and RSV acts via SIRT1. In the elderly, the SIRT1 remains antioxidant and RSV ceases its operation via SIRT1. RSV has an antioxidant action in both age groups, and that in aging there was a change in the cellular context characterized by the silencing of the AMPK pathway antioxidant character.
Assuntos
Proteínas Quinases Ativadas por AMP , Estilbenos , Proteínas Quinases Ativadas por AMP/metabolismo , Idoso , Envelhecimento , Humanos , Pessoa de Meia-Idade , Estresse Oxidativo , Resveratrol/farmacologia , Transdução de Sinais , Sirtuína 1/metabolismo , Estilbenos/farmacologiaRESUMO
Aging is characterized by a progressive loss of physiological integrity. One common denominator is the increase of reactive oxygen species (ROS) caused by inhibition of important antioxidant pathways. Resveratrol is a polyphenol known for its potent antioxidant activity. However, antioxidant pathways activated by them change with aging. The objective of our study was to verify the antioxidant effect of resveratrol in an oxidative stress environment in Human Mononuclear Cells (PBMC) from donors with different ages. Resveratrol (5 µM), a stimulus with H2O2 (0,64 % v/v) in addition to inhibitors of PKA, AkT/PKB and MAPK signaling pathways were used in chemiluminescence assay. An incresed basal production of ROS was observed in the elderly than in the middle-aged group. Resveratrol was able to reduce ROS in both groups, but with greater efficiency in the middle-aged group. By inhibiting PKA, Akt/PKB and MAPK signaling pathways we observed that resveratrol presented an altered performance in the aging process, changing signaling pattern of MAPK pathway.