Oxidative stress plays an essential role in the pathogenesis and progression of many conditions and diseases including aging, cardiovascular and dermatological diseases. Accumulating evidence, in fact, revealed the multiple mechanisms by which oxidants contribute to cellular damage(1). Oxidative stress is caused by the overproduction of reactive oxygen species (ROS), which include both the free radicals and their non-radical intermediates, such as superoxide anion (O2¿¿), hydroxyl ion (OH¿), hydrogen peroxide (H2O2) and peroxyl radicals (ROO¿), alkoxyl (RO¿), singlet oxygen (O2), and ozone (O3). The burst of ROS is associated with an imbalance between the generated ROS and the antioxidant defense systems. Evidence shows that oxidative stress plays an important role in the progression of various diseases, but its evaluation results controversial(2). This is partly due to the incorrect evaluation of biomarkers of oxidative stress, and in particular, to the lack of the assessment of key ROS-producing enzymes, such as Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). NADPH oxidase is a multisubunit enzyme complex that participates in the generation of superoxide or hydrogen peroxide (H2O2) and plays a key role in several biological functions. Among seven known NOX isoforms, NOX2 was the first identified in phagocytes but it is also expressed in several other cell types including endothelial cells, platelets, microglia, neurons and muscle cells. NOX2 has been assigned multiple roles in regulating many aspects of innate and adaptive immunity and human and mouse models of NOX2 genetic deletion highlighted this key role. On the other side, NOX2 hyperactivation is involved in the pathogenesis of several diseases with different etiologies but all are characterized by an increase in oxidative stress and inflammatory process(3). From this point of view, the evaluation and modulation of oxidative stress NOX2-mediated could represent an important tool to stratify and predict the onset and worsening associated to many diseases. Moreover, oxidative stress and inflammation are closely linked. Indeed, oxidative stress can cause inflammation, a pathological condition characterized by continued active inflammation response and tissue destruction that involves many of the immune cells directly or by production of inflammatory cytokine production. This, in turn, induces oxidative stress generating a vicious circle(4) that results in cell damage, which promotes a pro-inflammatory environment(4). Oxidative stress can also act as a signal in the intracellular pathways involved in normal cell growth and homeostasis, as well as in response to metabolic adaptations, immunity, differentiation and cell aging, the latter of which is an important characteristic in acute and chronic pathologies. To date, oxidative stress is assessed through indirect methodologies, which are expensive and difficult to apply in the clinical setting. This project would use a direct and effective method for evaluating oxidative stress. In particular, it will be evaluated and identified a soluble peptide fragment of NOX2 (sNOX2-dp) which is released into the circulation following activation of the enzyme during an inflammatory process. Thus, the measurement of oxidative stress levels of patients in different clinical conditions could enable to predict not only the severity of the inflammatory response but also its subsequent potential outcome. References 1. Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem. 2015;30(1):11-26. 2. Cammisotto V, Nocella C, Bartimoccia S, Sanguigni V, Francomano D, Sciarretta S, et al. The Role of Antioxidants Supplementation in Clinical Practice: Focus on Cardiovascular Risk Factors. Antioxidants (Basel). 2021;10(2). 3. Nocella C, D'Amico A, Cammisotto V, Bartimoccia S, Castellani V, Loffredo L, et al. Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies. Antioxidants (Basel). 2023;12(2). 4. Petrie JR, Guzik TJ, Touyz RM. Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. Can J Cardiol. 2018;34(5):575-84.
