Positive Aspects of Oxidative Stress at Different Levels of the Human Body: A Review

Abstract

Oxidative stress is the subject of numerous studies, most of them focusing on the negative effects exerted at both molecular and cellular levels, ignoring the possible benefits of free radicals. More and more people admit to having heard of the term "oxidative stress", but few of them understand the meaning of it. We summarized and analyzed the published literature data in order to emphasize the importance and adaptation mechanisms of basal oxidative stress. This review aims to provide an overview of the mechanisms underlying the positive effects of oxidative stress, highlighting these effects, as well as the risks for the population consuming higher doses than the recommended daily intake of antioxidants. The biological dose-response curve in oxidative stress is unpredictable as reactive species are clearly responsible for cellular degradation, whereas antioxidant therapies can alleviate senescence by maintaining redox balance; nevertheless, excessive doses of the latter can modify the redox balance of the cell, leading to a negative outcome. It can be stated that the presence of oxidative status or oxidative stress is a physiological condition with well-defined roles, yet these have been insufficiently researched and explored. The involvement of reactive oxygen species in the pathophysiology of some associated diseases is well-known and the involvement of antioxidant therapies in the processes of senescence, apoptosis, autophagy, and the maintenance of cellular homeostasis cannot be denied. All data in this review support the idea that oxidative stress is an undesirable phenomenon in high and long-term concentrations, but regular exposure is consistent with the hormetic theory.

Keywords: antioxidants; hormesis; neurodegeneration; oxidative stress; physical exercise.

Figure 1

Thiol (-SH) groups are susceptible to redox reactions, and at physiological pH values, they are found in an anionic form. The oxidation of this form generates a sulfenic derivative, which can reverse to its initial form through the disulfidic form, and, in this case, the protein can change its functionality.

Figure 2

Schematic representation of mitochondrial biogenesis pathways of influence and of reactive oxygen species (ROS). Antihyperlipidemic medication, such as fibrates and antihyperglycemic medication, such as thiazolidinedione derivatives, activate peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) via peroxisome proliferator-activated receptor γ and α (PPARα, PPARγ), respectively, and determine the onset of mitogenesis and the decrease in ROS levels. Similarly, caloric restriction or physical effort, via activation of the same receptors, following the activation of 5′ protein kinase by the AMP (AMPK) pathway, lead to the same processes.

Figure 3

Schematic representation of the mechanism by which caloric restriction and physical activity prolong the lifespan and improve health, using 5′ adenosine monophosphate-activated protein kinase (AMPK) and reactive oxygen species (ROS) as mediators, and ROS generated through oxidative phosphorylation (OXPHOS)—schematic mechanism.

Figure 4

In cellular homeostasis, nuclear factor erythroid 2-related factor (Nrf-2) stabilizes by attaching to Keap-1 in the cytoplasm. The appearance of a stressor/reactive oxygen species (ROS) generator, under the action of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase–protein kinase B (PI3K–Akt system), the thiol (-SH) groups belonging to Kelch-like ECH-associated protein 1 (Keap-1) are oxidized (S-S cross links). This leads to Nrf-2 dissociation and translocation in the nucleus, where it attaches to a specific sequence, antioxidant responsive element (ARE), thus increasing cellular antioxidant activity.

Figure 5

Mitochondrial dynamics through the 5′ adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor gamma coactivator 1-alpha (AMPK-PGC-1α) system, with increased expression of nuclear factor erythroid 1-related factor (Nrf-1), nuclear factor erythroid 1-related factor (Nrf-2), myocyte enhancer factor-2 (Mef2), and cAMP response element-binding protein (CREB). At the same time, in the AMPK pathway, an improvement in glycemic status can be observed, through translocation of glucose transporter GLUT4 in the cellular membrane. Regarding the immune system, reactive oxygen species (ROS) enhance the activity of mitogen-activated protein kinase (MAPK) and nuclear Factor kappa B (NF-kB), which further favors interleukin and cytokine secretion (IL-1β, IL-6, tumor necrosis factor, TNF).