Oxidative stress damage occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the ability of cells to detoxify or repair the resulting damage. Reactive oxygen species are highly reactive molecules containing oxygen, such as superoxide radicals, hydrogen peroxide, and hydroxyl radicals.
Under normal physiological conditions, ROS play essential roles in cell signaling, immune defense, and various metabolic processes. However, excessive ROS production, often due to factors such as environmental toxins, radiation, inflammation, or metabolic dysfunction, can overwhelm the body's antioxidant defenses, leading to oxidative stress.
Oxidative stress can damage cellular components such as lipids, proteins, and DNA, leading to various pathological consequences:
Lipid Peroxidation: ROS can attack lipids, particularly unsaturated fatty acids in cell membranes, leading to lipid peroxidation. This process generates lipid peroxides and other reactive byproducts that disrupt membrane integrity, alter membrane fluidity, and impair cellular function.
Protein Oxidation: ROS can oxidize amino acid residues in proteins, leading to structural changes, loss of function, and aggregation. Protein oxidation can impair enzymatic activity, disrupt signaling pathways, and contribute to the accumulation of damaged proteins associated with aging and neurodegenerative diseases.
DNA Damage: ROS can directly damage DNA, causing base modifications, single-strand breaks, and double-strand breaks. DNA damage can impair DNA replication and transcription, leading to mutations, chromosomal aberrations, and genomic instability associated with cancer and aging.
Cellular Dysfunction and Death: Prolonged oxidative stress can disrupt cellular homeostasis and trigger programmed cell death pathways, such as apoptosis and necrosis. Oxidative stress-induced cell death contributes to tissue damage and organ dysfunction observed in various diseases, including neurodegenerative disorders, cardiovascular diseases, and inflammatory conditions.
Inflammation and Immune Dysregulation: Oxidative stress can activate inflammatory pathways and immune responses, leading to the production of proinflammatory cytokines, chemokines, and reactive molecules. Chronic inflammation driven by oxidative stress can exacerbate tissue damage and contribute to the pathogenesis of chronic inflammatory diseases.
To mitigate oxidative stress damage, cells employ a network of antioxidant defenses, including enzymatic antioxidants (e.g., superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic antioxidants (e.g., vitamins C and E, glutathione). Enhancing antioxidant defenses through dietary interventions, lifestyle modifications, and pharmacological interventions is a potential strategy for reducing oxidative stress-related pathology and promoting health and longevity.
Oxidative stress is implicated in the progression of many neurological diseases, which could be induced by various chemicals, such as hydrogen peroxide (H2O2) and acrylamide.
Traumatic brain injury (TBI) is frequently associated with abnormal blood-brain barrier function, resulting in the release of factors that can be used as molecular biomarkers of TBI, among them GFAP, UCH-L1, S100B, and NSE. Although many experimental studies have been conducted, clinical consolidation of these biomarkers is still needed to increase the predictive power and reduce the poor outcome of TBI. Interestingly, several of these TBI biomarkers are oxidatively modified to carbonyl groups, indicating that markers of oxidative stress could be of predictive value for the selection of therapeutic strategies 1).
Oxidative stress is a major contributor to macrovascular complications of diabetes (MCD). Nuclear factor (erythroid-derived 2)-like 2 (NRF2) governs cellular antioxidant defense system by activating the transcription of various antioxidant genes, combating diabetes-induced oxidative stress. Accumulating experimental evidence has demonstrated that NRF2 activation protects against MCD. Structural inhibition of Kelch-like ECH-associated protein 1 (KEAP1) is a canonical way to activate NRF2. More recently, novel approaches, such as activation of the Nfe2l2 gene transcription, decreasing KEAP1 protein level by microRNA-induced degradation of Keap1 mRNA, prevention of proteasomal degradation of NRF2 protein and modulation of other upstream regulators of NRF2, have emerged in the prevention of MCD. A review of Wu et al. provided a brief introduction of the pathophysiology of MCD and the role of oxidative stress in the pathogenesis of MCD. By reviewing previous work on the activation of NRF2 in MCD, we summarize strategies to activate NRF2, providing clues for the future intervention of MCD. Controversies over NRF2 activation and future perspectives are also provided in this review 2).
Oxidative stress is considered as major culprit for neurodegenerative diseases and triggers cognitive and memory impairments.
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling.
In humans, oxidative stress is thought to be involved in the development of cancer, Parkinson's disease, Alzheimer's disease, atherosclerosis, heart failure, myocardial infarction, fragile X syndrome, Sickle Cell Disease, lichen planus, vitiligo, autism, infection, and chronic fatigue syndrome. However, reactive oxygen species can be beneficial, as they are used by the immune system as a way to attack and kill pathogens. Short-term oxidative stress may also be important in prevention of aging by induction of a process named mitohormesis.
Oxidative stress and the inflammatory response are thought to promote brain damage in the setting of subarachnoid hemorrhage (SAH).
Results indicate that puerarin can ameliorate oxidative neurodegeneration after TBI, at least in part, through the activation of PI3K-Akt pathway 3).