Acute hypoxia increases the formation of reactive oxygen species (ROS) in the brain. However, the effect of reoxygenation, unavoidable to achieve full recovery of the hypoxic organ, has not been clearly established. The aim of the present study was to evaluate the effects of exposition to acute severe respiratory hypoxia followed by reoxygenation on the evolution of oxidative stress and apoptosis in the brain. We investigated the effect of in vivo acute severe normobaric hypoxia (rats exposed to 7% O2 for 6h) and reoxygenation in normoxia (21% O2 for 24h or 48h) on oxidative stress markers, the antioxidant system and apoptosis in the brain. After respiratory hypoxia we found increased levels of HIF-1α expression, lipid peroxidation, protein oxidation and nitric oxide in brain extracts. Antioxidant defence systems such as superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GPx) and the reduced/oxidized glutathione (GSH/GSSG) ratio were significantly decreased in the brain. After 24h of reoxygenation, oxidative stress parameters and the anti-oxidant system returned to control values. Regarding the apoptosis parameters, acute hypoxia increased cytochrome c, AIF and caspase 3 activity in the brain. The apoptotic effect is greatest after 24h of reoxygenation. Immunohistochemistry suggests that CA3 and dentate gyrus in the hippocampus seem more susceptible to hypoxia than the cortex. Severe acute hypoxia increases oxidative damage, which in turn could activate apoptotic mechanisms. Our work is the first to demonstrate that after 24h of reoxygenation oxidative stress is attenuated, while apoptosis is maintained mainly in the hippocampus, which may, in fact, be the cause of impaired brain function.

In response to stress signal, nuclear factor‐erythroid 2‐related factor 2 (Nrf2) induces the expression of target genes involved in antioxidant defense and detoxification. Nrf2 activity is strictly regulated through a variety of mechanisms, including regulation of Keap1‐Nrf2 stability, transcriptional regulation (NF‐ĸB, ATF3, ATF4), and post‐transcriptional regulation (miRNA), evidencing that transcriptional responses of Nrf2 are critical for the maintenance of homeostasis. Ischemia‐reperfusion (IR) injury is a major cause of graft loss and dysfunction in clinical transplantation and organ resection. During the IR process, the generation of reactive oxygen species (ROS) leads to damage from oxidative stress, oxidation of biomolecules, and mitochondrial dysfunction. Oxidative stress can trigger apoptotic and necrotic cell death. Stress factors also result in the assembly of the inflammasome protein complex and the subsequent activation and secretion of proinflammatory cytokines. After Nrf2 activation, the downstream antioxidant upregulation can act as a primary cellular defense against the cytotoxic effects of oxidative stress and help to promote hepatic recovery during IR. The complex crosstalk between Nrf2 and cellular pathways in liver IR injury and the potential therapeutic target of the Nrf2 inducers will be discussed in the present review.

Ischemic stroke is characterized by the disruption of cerebral blood flow, which produces a central core of dead neurons surrounded by a penumbra of damaged but partially functional neurons. Many factors are associated with such brain injury, including excitotoxicity and free radicals. Recent clinical studies have shown that high plasma ferritin levels are detrimental in acute ischemic stroke. As an iron-storage protein, ferritin can act both as a scavenger and as a donor of free iron, which is a source of hydroxyl radicals. Following disruption of the blood-brain barrier, the ferritin and the free iron that have accumulated in endothelial cells in brain capillaries, together with plasma ferritin, can enter the penumbra. Iron-dependent oxidative stress in the penumbra can lead to necrosis and further neurological deterioration following ischemic stroke. An excess of iron should be considered pathological in the ischemic brain. Therapeutic strategies for ischemic stroke should attempt to restore brain function within the penumbra. Consequently, the iron content of systemic stores should be measured, and anti-oxidant treatment should be considered when it is excessive.

MicroRNAs (miRNAs) are small RNAs that do not encode for proteins and play key roles in the regulation of gene expression. miRNAs are involved in a comprehensive range of biological processes such as cell cycle control, apoptosis, and several developmental and physiological processes. Oxidative stress can affect the expression levels of multiple miRNAs and, conversely, miRNAs may regulate the expression of redox sensors, alter critical components of the cellular antioxidants, interact with the proteasome, and affect DNA repair systems. The number of publications identifying redox-sensitive miRNAs has increased significantly over the last few years, and some miRNA targets such as Nrf2, SIRT1 and NF-κB have been identified. The complex interplay between miRNAs and ROS is discussed together with their role in myocardial ischemia-reperfusion injury and the potential use of circulating miRNAs as biomarkers of myocardial infarction. Detailed knowledge of redox-sensitive miRNAs is needed to be able to effectively use individual compounds or sets of miRNA-modulating compounds to improve the health-related outcomes associated with different diseases.

Hypothermia is a condition in which core temperature drops below the level necessary to maintain bodily functions. The decrease in temperature may disrupt some physiological systems of the body, including alterations in microcirculation and reduction of oxygen supply to tissues. The lack of oxygen can induce the generation of reactive oxygen and nitrogen free radicals (RONS), followed by oxidative stress, and finally, apoptosis and/or necrosis. Furthermore, since the hypothermia is inevitably followed by a rewarming process, we should also consider its effects. Despite hypothermia and rewarming inducing injury, many benefits of hypothermia have been demonstrated when used to preserve brain, cardiac, hepatic, and intestinal function against ischemic injury. This review gives an overview of the effects of hypothermia and rewarming on the oxidant/antioxidant balance and provides hypothesis for the role of reactive oxygen species in therapeutic hypothermia.

Nitric oxide (NO ⋅) has a complex role in the inflammatory response. In this study, we modified the levels of endogenous NO ⋅ in vivo in an acute model of inflammation and evaluated the interactions between NO ⋅ and superoxide anion ([ ]) produced by polymorphonuclear leukocytes (PMNs) accumulated in the inflamed area. We injected phosphate-buffered saline (control group), 6 μmol ofl- N ⁵-(1-iminoethyl)ornithine (l-NIO group), or 6 μmol ofl-arginine (l-arginine group) into the granuloma pouch induced by carrageenan in rats.[ ] plus[ ] (indicative of NO ⋅ generation) was 188 nmol in the exudate of the control group, but it decreased in the l-NIO group ( P < 0.05) and increased in thel-arginine group ( P < 0.05). When PMNs from treated rats were incubated in vitro, the production of superoxide anion ([ ]) decreased by ∼46% in thel-arginine group. Furthermore,[ ] was inhibited in PMNs whenl-arginine was added to the incubation medium before phorbol 12-myristate 13-acetate stimulation but not when added simultaneously. Our results suggest a protective role for NO ⋅ in inflammation, through the inactivation of NADPH oxidase and the consequent impairment of[ ] production for cell-mediated injury.