Reactive oxygen (ROS) and nitrogen (RNS) species are generated as by-products of normal cellular metabolic activities and have been implicated in the pathogenesis of a variety of diseases. Disruption of normal cellular homeostasis by redox signaling may result in chronic infections, inflammatory disorders, cardiovascular and neurodegenerative diseases, and cancer.

Notwithstanding that the multiple roles of oxidative stress in human normal biology and pathology have been intensely discussed over the last half-a-century, the problem is still far beyond our full comprehension. Thus, in a comparatively short history of oxidative medicine, the roles free radicals and antioxidants have been entirely redefined. Some negative actions of free radicals and ROS in human biology and pathology, widely recognized two-three decades ago, have been subsequently transformed into positive ones, in appreciation of their essential impact in the intracellular signaling on the organism’s defense against biotic and abiotic stresses. On the other hand, the great hope that direct antioxidants could be the panacea resolving practically all health problems has vanished, due to the growing number of inconclusive or negative data from epidemiological and clinical studies. The current state of uncertainty regarding the feasibility of antioxidant therapy is partly due to methodological pitfalls in drug development and delivery, the limited and often overlooked knowledge regarding antioxidant metabolism and their interaction with physiologically important molecular/cellular processes in the organism, and the lack of correlations between biological markers of oxidative stress and clinical outcomes. Modulation of oxidative stress is important to develop new therapies to manage a variety of conditions for which current therapies are not effective.

The main aim of this Special Issue is to address different pharmaceutical and pharmacological aspects of research related to the modulation of oxidative stress. Both original research articles and review articles discussing the current state of the art are welcomed.

Potential topics include but are not limited to the following:

• Synthesis and derivatization of antioxidant compounds with potential pharmacological applications to modulate their antioxidant properties and bioavailability, and synthesis of multifunctional molecules: metal chelation, radical scavenging, acetylcholinesterase/MAO inhibition, inhibition of protein aggregation (amyloid beta, alpha-synuclein etc.)
• Interactions of antioxidant compounds with signaling pathways such as: Nrf2/ARE, insulin (insulin action and resistance), inflammation
• NADPH oxidase inhibitors as antioxidant compounds and their therapeutic potential
• Pharmacokinetics and metabolic pathways of antioxidants and antioxidant activity of metabolites
• Antioxidant delivery systems with a focus on optimization and targeted delivery
• In vitro and in vivo studies on the pharmacological activity of antioxidants
• Epidemiological and clinical studies of antioxidant therapies
• Systematic reviews or meta-analysis of anti-oxidant trials
• Discrepancy between RCTs and long-term follow-up studies
• Biological markers to assess in vivo antioxidant/prooxidant actions, the correlation with clinical efficacy, and imaging of redox compounds/reactions in brain in vivo