Cellular Redox Mechanisms in Inflammation and Programmed Cell Death

Redox reactions play an important role in the regulation of various physiological processes, resulting in the diversity of articles featured in this Special Issue (SI), from works studying mechanisms of antioxidant activity to a prospective randomized study of the effects of hypoxia–hyperoxia exposures on metabolic products of the intestinal microbiome in patients. In vitro, microbiota metabolites formed under inflammation and sepsis inhibit cyclooxygenase peroxidase activity. Macrophages are the most persistent cells at inflammatory sites, with phenotypes differing not only in cytokine secretion but also in the production of reactive oxygen species (ROS). Neuronal dysfunction and pain may be caused by an imbalance in ROS/reactive nitrogen species (RNS) and antioxidant defense; thus, compounds with antioxidant properties can be promising therapeutic agents to mitigate oxidative stress and alleviate pathological conditions. An example of this is manganese porphyrins, which target key pathways involved in neuropathic pain. In this SI, flavonoids, polyphenols, and selenium compounds are studied for their protective ability against inflammation and oxidative injury. Pre-treatment with ferroptosis inhibitors or maintenance of mitochondrial functions enables the safe rewarming of cooled cells. In contrast, excess glutamate triggers a cascade of oxidative and metabolic disorders causing neuronal ferroptosis, with mitochondria playing a central role in this vulnerability. While diverse in biological models, the articles in this SI all demonstrate that ROS/RNS disorder is both a driver of pathology and a target for therapeutic intervention.