The pathogenesis of sepsis and its progression to multiple organ dysfunction syndrome and septic shock have been the subject of investigations for nearly half a century. Controversies still exist with regard to understanding the molecular pathophysiology of sepsis in relation to the complex roles played by reactive oxygen species, nitric oxide, complements and cytokines. In the present review we categorise the key turning points in sepsis development and outline the most probable sequence of events leading to cellular dysfunction and organ failure under septic conditions. We have applied an integrative approach in order to fuse current state-of-the-art knowledge about redox processes involving hydrogen peroxide, nitric oxide, superoxide, peroxynitrite and hydroxyl radical, which lead to mitochondrial respiratory dysfunction. Finally, from this point of view, the potential of redox therapy targeting sepsis is discussed.

Radicava™ (Edaravone) was approved the Food and Drug Administration (FDA) as a new treatment for amyotrophic lateral sclerosis (ALS). Edaravone is a synthetic antioxidant that specifically targets oxidative damage interacting with lipid radicals in the cell. In ALS disease the multiple cell types are involved in devastating loss of motor neurons. Mutations and biochemical changes in various cell types jointly contribute to motor neuron death, disease onset, and disease progression. The overall mechanism of neurodegeneration in ALS is still not completely understood. Dying motor neurons have been reported to exhibit features of apoptosis. However, non-apoptotic features of dying motor neurons have also been reported such as ferroptosis. The role of Edaravone in the prevention of ferroptosis in parallel with other therapeutic approaches to ALS therapy is discussed.

The present review is aimed at elucidating the neonatal 'sepsis redox cycle' - the cascade of inflammatory and redox events involved in the pathogenesis of sepsis in neonates. While adult and neonatal sepses share some common features, there are some substantial differences: higher mortality rates occur in adult sepsis and worse long-term effects are evident in neonatal sepsis survivors. Such epidemiological data may be explained by the lower ability of IL6 and IL8 to activate NF-κB-regulated transcription in neonatal sepsis in comparison to TNF-α, which is involved in the mechanisms of adult sepsis. The activation of NF-κB in neonatal sepsis is further promoted by hydrogen peroxide and results in mitochondrial dysfunction and energy failure as septic neonates experience decreased O2 consumption as well as lower heat production and body temperature in comparison to healthy peers. In neonates, specific organs that are still under development are vulnerable to sepsis-provoked stress, which may lead to brain, lung, and heart injury, as well as vision and hearing impairments. In the light of the processes integrated here, it is clear that therapeutic approaches should also target specific steps in the neonatal 'sepsis redox cycle' in addition to the current therapeutic approach that is mainly focused on pathogen eradication.

Pectin is the main soluble fiber in apples or citruses. It may be fermented by gut microbiota to metabolites showing local intestinal and systemic effects. A wide range of beneficial effects of dietary pectin includes impacts on the redox milieu and microbiota profile. We prepared pectin-derived oligosaccharides (apple (APDO) and citrus) and polygalacturonic acid-derived oligosaccharides, using alkaline hydrolysis by hydrogen peroxide, and analyzed them by Fourier Transform Infrared spectrometry. Furthermore, we analyzed the effects of pectin-derived oligosaccharides on hydroxyl radical (HO)-generating Fenton reaction using electron paramagnetic resonance spin-trapping spectroscopy, and the effects on the growth of Escherichia coli and Staphylococcus aureus in the presence of dietary-relevant HO-generating system (iron+ascorbate). The oligosaccharides react with HO radical to produce carbon dioxide radical anion (CO2-). A comparative analysis showed that APDO has the most prominent bacteriostatic effect. This might be at least partially related to the higher capacity of APDO to produce CO2-, which specifically targets proteins and appears to have a longer lifetime and larger diffusion radius in biological systems compared to HO.

In physiological settings, biliverdin and Cu²⁺build a paramagnetic complex with formal structure: radical cation/Cu¹⁺or radical anion/Cu³⁺.