Homeostatic control of redox status and health

Abstract

Research on oxidants and electrophiles has shifted from focusing on damage to biomolecules to the more fine-grained physiological arena. Redox transitions as excursions from a steady-state redox set point are continually ongoing in maintenance of redox balance. Current excitement on these topics results from the fact that recent research provided mechanistic insight, which gives rise to more concrete and differentiated questions. This Commentary focuses on redox eustress and the feedback restoration of steady state as concepts in active maintenance of physiological health, with brief discussion of redox stress response to viral infection, exemplified by COVID-19.

Sepsis, pyruvate, and mitochondria energy supply chain shortage

“…1,10,11 First, during resistance, excessive inflammation activation generates reactive oxygen species inducing oxidative stress within the microvasculature that can precipitate septic shock. 12,13 Second, the low-energy supply and antioxidative disease tolerance compromise immune and vital organ cells' abilities to promote growth and reverse immunometabolic paralysis. 14 Figure 1 is a simplified scheme of the infection-induced trade-off between the high energy resistance and low energy disease tolerance phenotypes that is imbedded in our previous understanding of proinflammatory and anti-inflammatory responses in sepsis.…”

“…Sepsis, however, fails the host's resistance‐to‐tolerance shift in 2 ways 1,10,11 . First, during resistance, excessive inflammation activation generates reactive oxygen species inducing oxidative stress within the microvasculature that can precipitate septic shock 12,13 . Second, the low‐energy supply and antioxidative disease tolerance compromise immune and vital organ cells’ abilities to promote growth and reverse immunometabolic paralysis 14 .…”

Influence of Oxidative Stress and Inflammation on Nutritional Status and Neural Plasticity: New Perspectives on Post-Stroke Neurorehabilitative Outcome

“…Free radicals are short-living reactive chemical species that, under physiological conditions, remain confined to their site of formation because of their short life span and endogenous antioxidant defense mechanisms that counteract their progression and damaging oxidative effects. A disturbance in this balance leads to oxidative stress, which causes damage to important macromolecules such as DNA, proteins, and lipids, resulting in the production of oxidative metabolites that persist in the systemic circulation as critical elements with multiple functional targets [ 43 , 44 , 45 , 46 ]. As is widely known, a strong relationship exists between oxidative stress and inflammation.…”

“…Free radicals such as superoxide, nitric oxide, and hydroxyl radicals, and other reactive species such as hydrogen peroxide, peroxynitrite, and hypochlorous acid, when over-produced, as in the case of an ischemic stroke, start complex chain reactions leading to the production of oxidative metabolites capable of maintaining oxidative stress in the systemic circulation and thus interfering as critical factors with multiple functional targets [ 43 , 44 ]. A wide array of enzymatic and non-enzymatic compounds acting as antioxidants have been ascribed to play a crucial role by synergically cooperating to maintain the homeostasis of redox balance and inflammation [ 44 ]. The neuronal redox state represents a particular model of homeostatic equilibrium that is established between the generation of radicals and the antioxidant defense.…”

A Dynamic Model for Estimating the Interaction of ROS–PUFA–Antioxidants in Rabbit

“…When the primary defences are not sufficient, other mechanisms, such as transcription of genes and transduction of essential proteins, interfere with the oxidative response (i.e., the cytochrome P450 [CYP450] family [32]). Furthermore, the tocopheroxyl radical can be reduced back to tocopherol by the activity of a redox antioxidant system that includes AA and thiol-dependent enzymes (e.g., glutathione reductase) as the main players [12], and the scavenging function of vitamin E (Vit E) cooperates with that of the membrane peroxidase, especially phospholipid hydroperoxide 4 (GPx4) [33].…”