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Background: One of the most studied theories about aging comes from the accumulation of free radical generation, leading to oxidative stress. Resveratrol (RSV) is a polyphenolic compound that has been shown to act as an antioxidant in medical practice. Objective: To verify the antioxidant action of resveratrol (and its correlation with aging) in leukocytes from donors of different ages, mainly through the analysis of the three main enzymes of the antioxidant complex and the analysis of the SIRT1 signaling pathway. Methods: Luminol-dependent chemiluminescence assay was used to evaluate ROS and SIRT1. Antioxidant enzymes were evaluated by commercial kits. *p<0.05. Results: In all age groups, there was a reduction in reactive oxygen species (ROS) in cells stimulated with RSV. There was a positive correlation between its antioxidant effect and donor age. In younger individuals (20-39 years old), there was an increase in catalase activity in cells exposed to RSV. In the older groups (40-59 years old and 60-80 years old), RSV was able to increase the activity of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). Through the analysis of SIRT1 it was possible to observe a silencing of the pathway in leukocytes treated with RSV during aging. Conclusion: RSV showed antioxidant activity in all age groups, although more pronounced in younger individuals. One of the mechanisms of action of the RSV is due to the increase in the activity of antioxidant enzymes, which varies according to the individual's age, especially through the modulation of important antioxidant pathways.

Introduction:Despite advances in treatment of diabetes mellitus, its prevalence continues to rise globally. Medications available are unable to control the vascular complications. Proposals for new therapeutic targets must take into account the hyperglycemia-induced signaling pathways that give rise to the inflammatory profile of the disease.Areas covered:How high-mobility-group box-1 (HMGB1) protein, acting as an activator of Toll-like receptors (TLR) and receptors for advanced glycation end products (RAGE), creates a functional tripod that contributes to increased production of pro-inflammatory mediators, and sustains the chronic inflammatory state associated with diabetes. The interaction of TLR2 and TRL4 with host-derived ligands, which links diabetic complications with the innate immune response, and the activation of RAGE, which induces a cascade of metabolic responses, leading to the production and secretion of pro-inflammatory cytokines.Expert opinion:Considering the involvement of the innate immune system, in association with the role of HMGB1 as an activator of TLR and RAGE, diabetes should be considered and treated as a metabolic and immunological disease, triggered by hyperglycemia. HMGB1 plays a central role in mediating injury and inflammation, and interactions involving HMGB1––TLR––RAGE constitute a tripod that trigger NF-κκB activation. Blockade or downregulation of HMGB1, and/or control of the inflammatory tripod, represent a promising therapeutic approach for the treatment of diabetes.

Background: Diabetes mellitus constitutes a serious public health problem. Recent advances in therapies are unable to control its vascular complications. New medications have been suggested but without comprehensive knowledge of the signaling pathways induced by hyperglycemia. Objective: To review the mechanisms of the inducer and effector phases of the metabolic cascade in diabetes, with emphasis on the steps that have been targeted to date The route from hyperglycemia to advanced glycation end products (AGE)–receptor of advanced glycation end products (RAGE) complex formation is suggested as a target for new therapies. Methods: A review of literature, including historical papers and recent manuscripts. Results: All the components of the suggested route are initially activated or indirectly formed due to hyperglycemia via a two-phase cascade that represents a dangerous metabolic route, especially for diabetics. Recent experiments with new drugs and clinical trials targeting this pathway are examined. Conclusions: In order to control vascular injury in diabetes, several steps in the cascade need to be inhibited simultaneously together with aggressive glycemic control.

Background: Diabetes is associated with a pro-inflammatory status characterized by an increased production of inflammatory molecules. Reactive Oxygen Species (ROS) and cAMP elevating agents represent two molecular systems, normally generated during inflammation. These molecules could be responsible for the alteration of signaling pathways. In the present paper we have studied the correlation between ROS generation and inositolpolyphosphates (InsP1, InsP2 InsP3 and InsP4) released by granulocytes from Type 1 diabetic patients (DM1) in the presence or in the absence of cyclic AMP-elevating agents. The effect of cAMP on ROS production was quantified in a chemoluminescence assay luminol-dependent (RLU/min). InsP1, InsP2 InsP3 and InsP4 were quantified by inositol-H3 in a Beta-counter and the results were expressed as count per minute (CPM). The elevation of intracellular level of cAMP inhibited both InsP3 and ROS production in granulocytes from healthy subjects and activated in the cells from Type 1 diabetic patients. InsP1, InsP2 and InsP4 did not show significant alteration in both studied cells. There was a significant correlation between InsP3 and ROS in the presence of elevated content of cAMP. This correlation was observed in a 15 minutes reaction for healthy subjects and in 120 minutes for DM1. The importance of both InsP3 release and ROS production in an inflammatory process and tissue pathophysiology in Type 1 diabetic patients is still under debate because hyperglycemia accelerates generation of oxidative stress and may play an important role in the development of complications in diabetes. Thus, our results demonstrated alteration in metabolic response in granulocytes from Type 1 diabetic patients and it may be important for the development of therapeutic processes and drugs that interfere with signaling of ROS generation and may contribute to the improvement of the severe complications of diabetes.