Table of Contents
Overview
Definition of Oxidative Stress
Oxidative stress (OS) is defined as the physiological condition that occurs when there is an imbalance between pro-oxidants and antioxidants, favoring the former, which leads to molecular and cellular damage due to oxidation.[1.1] The concept of oxidative stress was first introduced in 1985, highlighting the disruption in redox signaling and control caused by the excess of oxidants that attack cells, countered by antioxidants.[4.1] This imbalance is primarily triggered by the overproduction of reactive oxygen species (ROS) and their inadequate elimination by the antioxidant system.[3.1] While ROS can function as second messengers under physiological conditions, their overproduction is associated with the onset and progression of various diseases, including neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease.[5.1] The significance of oxidative stress in redox biology and medicine has garnered extensive interest and research, emphasizing its role in understanding the damaging processes occurring within cells.[6.1]Mechanisms and Effects
Oxidative stress results from an imbalance between reactive oxygen species (ROS) production and the body's antioxidant defenses, leading to cellular damage. This imbalance is particularly critical during tissue repair, where increased oxygen consumption elevates ROS and reactive nitrogen species (RNS) levels, impairing repair mechanisms by damaging lipids, proteins, and DNA.[8.1] Cells counteract oxidative stress through mechanisms integral to normal physiology, such as pathways promoting cell survival or programmed cell death. The oxidative stress response is one of several cellular defenses activated against harmful stimuli, alongside heat shock and DNA damage responses.[9.1] Environmental pollutants, including ozone, nitrogen oxides, and particulates, significantly contribute to oxidative stress by disrupting redox balance and generating ROS.[12.1] This stress can trigger inflammatory responses, potentially leading to apoptosis or cell death if damage remains unresolved.[11.1] Understanding these cellular responses and environmental impacts is crucial for addressing oxidative stress's health effects. Air pollution, particularly particulate matter less than 2.5 micrometers (PM2.5), is a leading global environmental risk factor, contributing to numerous health issues and deaths.[14.1] The health effects of air pollution involve inflammation and oxidative stress, impacting tissues like the lungs and heart.[13.1] Exposure to pollutants, cigarette smoke, and UV radiation disrupts the pro-oxidant and antioxidant balance, increasing oxidative stress.[15.1] This imbalance occurs when ROS production exceeds the body's neutralization capacity, causing cellular damage.[16.1] Understanding these mechanisms is vital for developing strategies to mitigate pollutant exposure and reduce health impacts. Oxidative stress significantly influences central nervous system (CNS) diseases, such as Alzheimer's and stroke, due to the brain's vulnerability to oxidative damage.[17.1] Mitochondrial dysfunction and oxidative stress play critical roles in neurodegenerative disease pathogenesis, with mitochondrial dysfunction in neurons leading to energy metabolism disorders and cell death, potentially triggering CNS dysfunction.[20.1] Oxidative stress is also linked to tau hyperphosphorylation and synapse dysfunction, highlighting the need for therapeutic strategies to prevent Alzheimer's disease.[18.1] Emerging research suggests that addressing mitochondrial dysfunction and oxidative stress through enhanced mitochondrial biogenesis and antioxidant defenses may offer promising treatment avenues for neurodegenerative diseases.[20.1] Additionally, exploring intracellular antioxidant mechanisms to reduce ROS is crucial, as deficiencies can contribute to neurodegenerative disorder progression.[19.1]In this section:
History
Early Research and Concepts
Early research on oxidative stress (OS) defined it as an imbalance between oxidants and antioxidants, with a predominance of oxidants, leading to a disruption of redox signaling and control, as well as potential molecular damage.[46.1] This discovery not only highlighted these critical biochemical processes but also opened an exciting field of study regarding the membrane transport of hydrogen peroxide by peroxiporins.[46.1] This foundational understanding has significantly advanced our knowledge of oxidative stress mechanisms and their implications in biological systems, paving the way for further investigations into its role in various biological processes and diseases.[46.1] The relevance of hydrogen peroxide transport by peroxiporins in health and disease underscores the importance of this research area.[46.1]Evolution of the Oxidative Stress Paradigm
The concept of oxidative stress was first formulated in 1985 and is defined as an imbalance between oxidants and antioxidants that favors oxidants, leading to a disruption of redox signaling and potential molecular damage.[50.1] Since its introduction, the oxidative stress paradigm has experienced significant development within the broader field of redox biology and medicine.[51.1] This concept is now widely accepted and extensively utilized in both basic and applied biological sciences.[47.1] Research has uncovered molecular mechanisms by which reactive oxygen species (ROS) induce the up-regulation of antioxidant enzymes, particularly through the ROS-sensitive Nrf2/Keap1 system, which responds to mild oxidative stress by modifying cysteine residues in the sensor protein Keap1.[47.1] The early research on oxidative stress primarily focused on understanding the basic principles of stress responses, which were initially conceptualized by Hans Selye in 1936. However, the specific framework of oxidative stress emerged later, leading to significant advancements in redox biology and medicine over the past three decades.[51.1] As the field evolved, it became clear that oxidative stress plays a critical role in the pathogenesis of various diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders.[52.1] The concept of oxidative stress has undergone significant development over the past 30 years, becoming a well-accepted and extensively utilized framework in both basic and applied fields of biology and medicine.[47.1] Defined as "an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage," oxidative stress plays a crucial role in various biological processes.[50.1] Its regulation is particularly important in tumor development and responses to anticancer therapies, highlighting its relevance in cancer research.[48.1] Furthermore, the discovery of molecular mechanisms, such as the ROS-sensitive Nrf2/Keap1 system, has enhanced our understanding of how organisms respond to mild oxidative stress.[47.1] This growing recognition of oxidative stress underscores its significance in understanding health and disease across diverse scientific disciplines.[47.1]Recent Advancements
Current Understanding of Oxidative Stress in Disease
Oxidative stress (OS) is increasingly recognized as a critical factor in the pathogenesis of various diseases, including diabetes, cancer, and neurological disorders. Defined as an imbalance between reactive oxygen species (ROS) and antioxidants, oxidative stress leads to significant molecular damage, affecting proteins, lipids, and DNA.[96.1] The concept of oxidative stress was first introduced in 1985, highlighting the detrimental effects of oxidants on biological systems and prompting extensive research into its implications for health and disease.[97.1] Recent basic and clinical studies have uncovered new insights into the role of oxidative stress in diabetic complications, suggesting innovative approaches to causal antioxidant therapy.[102.1] Modern therapeutic strategies in the treatment of diabetes mellitus are focused on developing personalized antioxidant therapies that target specific sources of reactive oxygen species (ROS) while improving antioxidant delivery methods.[103.1] Additionally, oxidative stress, primarily driven by ROS, plays a significant role in the development and progression of cancer, contributing to various pathological conditions, including diabetes and metabolic disorders.[104.1] This highlights the importance of addressing oxidative stress in the pathogenesis of age-related chronic diseases, such as diabetes and neurological disorders, and emphasizes the need for continued progress in developing therapeutics based on antioxidants and other related compounds.[105.1] In addition to diabetes and cancer, oxidative stress is also linked to neurological disorders such as Alzheimer's and Parkinson's diseases. Excessive ROS can lead to cellular damage that exacerbates these conditions, highlighting the importance of antioxidants in therapeutic strategies aimed at neuroprotection.[105.1] The interplay between oxidative stress and inflammation further complicates these diseases, suggesting that comprehensive treatment approaches must consider both factors.[101.1]In this section:
Physiological Roles Of Reactive Oxygen Species
Cell Signaling Functions
Reactive oxygen species (ROS) play a crucial role in cellular signaling, acting as second messengers that facilitate various physiological processes. Among the different types of ROS, hydrogen peroxide (H₂O₂) is particularly significant due to its ability to fulfill the requirements of a second messenger, including its specific enzymatic production and degradation, which provide temporal and spatial specificity in signaling pathways.[173.1] The Hippo signaling pathway, known for its involvement in cell differentiation, proliferation, survival, and tissue regeneration, has recently been linked to the regulation of oxidative stress and ROS.[175.1] This connection underscores the importance of ROS in maintaining cellular homeostasis and promoting survival under stress conditions. Furthermore, in cancer cells, high levels of ROS are generated to activate signaling pathways that enhance proliferation and metabolic adaptation, while simultaneously maintaining antioxidant defenses to prevent excessive oxidative damage.[177.1] In various experimental models, alterations in ROS levels have demonstrated both beneficial and detrimental effects. For instance, the deletion of the Prx1 gene in mice leads to increased ROS production and oxidative damage, ultimately resulting in a decreased lifespan.[176.1] Conversely, certain genetic modifications in yeast that elevate intracellular ROS levels can paradoxically extend lifespan, highlighting the complex role of ROS in cellular aging and stress responses.[176.1]Balance Between Oxidants and Antioxidants
Oxidative stress is characterized by an imbalance between the production of reactive oxygen species (ROS) and the ability of cells to detoxify them, leading to significant disruptions in normal cellular function, inflammation, tissue injury, and organ dysfunction.[137.1] Under physiological conditions, a certain level of ROS is necessary for various biological processes, including cell signaling and the regulation of biochemical transformations.[136.1] This state, referred to as oxidative eustress or "good stress," is marked by low to mild levels of oxidants that facilitate essential cellular functions.[135.1] However, excessive production of ROS, often triggered by environmental stressors such as UV radiation, pollutants, and heavy metals, can overwhelm the body's antioxidant defenses, resulting in oxidative stress.[136.1] This overproduction is linked to numerous disorders, including neurodegenerative diseases, where oxidative stress contributes to mitochondrial dysfunction and neuronal death.[144.1] The dual nature of ROS, acting as both signaling molecules and damaging agents, complicates the understanding of their roles in health and disease.[139.1] Antioxidants play a crucial role in neutralizing free radicals and mitigating oxidative stress, thus maintaining the delicate balance between oxidants and antioxidants.[145.1] Research into natural compounds with antioxidant properties is ongoing, as these may offer promising therapeutic strategies for managing oxidative stress-related diseases.[145.1] The challenge remains in effectively targeting oxidative stress to harness the beneficial aspects of ROS while minimizing their harmful effects, particularly in the context of chronic diseases.[142.1]Implications In Health And Disease
Chronic Diseases Associated with Oxidative Stress
Oxidative stress is an unavoidable consequence of life in an oxygen-rich atmosphere, defined as the disturbance of the delicate balance between oxidants and antioxidants in favor of the oxidants. This imbalance leads to a disruption of redox signaling and control, as well as direct molecular damage.[179.1] In living organisms, oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species (ROS) and the biological system's ability to detoxify these reactive intermediates or repair the resulting damage. Such disturbances can cause toxic effects through the production of peroxides and free radicals, damaging all cellular components, including proteins, lipids, and DNA.[180.1] Oxidative stress is implicated in various chronic diseases, including cardiovascular disease and cancer, as exacerbated oxidative stress leads to the accelerated formation of advanced glycation end products (AGEs), which are a complex mixture of crosslinked proteins and protein modifications.[182.1] Additionally, oxidative stress plays a significant role in the pathogenesis of AGE-related chronic diseases, including diabetes and neurological disorders.[183.1] In the context of cancer, oxidative stress affects genomic stability and alters signaling pathways within the cellular microenvironment, making cancer cells more susceptible to oxidative stress-induced apoptosis.[186.1] This modulation of ROS can influence critical signaling pathways, including those involving tumor suppressor genes, thereby contributing to cancer development.[186.1] Furthermore, oxidative stress has been linked to neurological disorders, including Alzheimer's disease and Parkinson's disease, where it exacerbates cellular damage and contributes to disease progression.[184.1] The identification of multiple biomarkers associated with oxidative stress has facilitated the understanding of its implications in health and disease. These biomarkers reflect damage to various molecular classes, including proteins, lipids, carbohydrates, and DNA, highlighting the extensive impact of oxidative stress on cellular integrity.[181.1] As research continues to elucidate the mechanisms by which oxidative stress contributes to chronic diseases, it becomes increasingly clear that addressing oxidative stress through therapeutic interventions, such as antioxidants and AGE breakers, may offer potential strategies for disease prevention and management.[184.1]Antioxidants And Their Mechanisms
Types of Antioxidants
Antioxidants can be classified into various types based on their sources and mechanisms of action, including endogenous antioxidants, dietary antioxidants, and synthetic antioxidants. Endogenous antioxidants are produced within the body and are essential for modulating levels of reactive oxygen species (ROS), which play critical roles in physiological functions while minimizing oxidative damage.[240.1] Dietary antioxidants, primarily sourced from a diverse array of plant-based foods, have been linked to a reduced risk of chronic diseases such as cancer, heart disease, and stroke. To enhance antioxidant intake, it is recommended to consume a variety of antioxidant-rich plant foods.[234.1] Antioxidants function by hindering oxidative processes, thereby delaying or preventing oxidative stress, which is associated with significant health issues, including cardiovascular disease and cancer.[244.1] Understanding the mechanisms of action of these antioxidants is crucial for developing effective strategies to combat diseases related to oxidative stress.[240.1] Antioxidants are essential for maintaining health, and polyphenols, a category of dietary antioxidants, are particularly noteworthy. Research indicates that individuals who consume polyphenol-rich diets—specifically, more than 650 milligrams per day—exhibit lower mortality risks compared to those who consume less than 500 milligrams per day.[256.1] Foods abundant in polyphenols include apples, berries, broccoli, carrots, chili peppers, cumin, and dark chocolate, with cocoa being a significant source.[258.1] Notably, cocoa powder is recognized for its high polyphenol content, containing 3,448 mg of polyphenols per 100 grams.[259.1] Additionally, red beans are a valuable source of polyphenols and possess potent antioxidant properties, while red raspberries are rich in antioxidants such as vitamin C and flavonoids, including cyanidin and quercetin.[257.1] Incorporating these foods into a balanced diet can enhance antioxidant intake and support overall health. Antioxidants play a crucial role in protecting the body from oxidative stress, with vitamins such as vitamin C and vitamin E being significant dietary sources. These vitamins are known to prevent oxidative modification of low-density lipoproteins, which is essential for cardiovascular health.[241.1] The mechanisms of action of these antioxidants include scavenging reactive oxygen and nitrogen species, as well as contributing to redox signaling and the generation of bioactive secondary metabolites.[242.1] Furthermore, the effectiveness of natural antioxidants in inhibiting oxidative stress is influenced by various factors, including their chemical structures and concentrations at the reaction site.[243.1] This highlights the complexity of antioxidant action and the importance of understanding their specific mechanisms to enhance their protective effects against oxidative damage. In addition to natural sources, synthetic antioxidants have been developed for therapeutic purposes. These compounds aim to mimic the action of natural antioxidants and are utilized in various medical applications to mitigate oxidative stress-related diseases.[240.1] However, the effectiveness of both natural and synthetic antioxidants can vary based on their chemical structures, concentrations, and the specific oxidative stress conditions they are intended to address.[243.1]Mechanisms of Action in Disease Prevention
Antioxidants play a crucial role in mitigating oxidative stress, which is characterized by an imbalance between reactive oxygen species (ROS) and the body's antioxidant defenses. This imbalance can lead to cellular damage and is implicated in the pathogenesis of various chronic diseases, including cardiovascular diseases, cancer, and neurodegenerative disorders.[223.1] The mechanisms through which antioxidants exert their protective effects involve both endogenous and exogenous sources. Antioxidants are essential in managing oxidative stress, which is implicated in various chronic diseases. They can be categorized into endogenous antioxidants, produced within the body, and exogenous antioxidants, sourced from dietary intake. The body's antioxidant defense network modulates levels of reactive oxygen species (ROS), allowing for their physiological functions while minimizing oxidative damage that can lead to disease development.[222.1] Exogenous antioxidants, particularly phytochemicals found in a wide range of foods and medicinal plants, play a pivotal role in preventing and treating diseases associated with oxidative stress. These compounds, including polyphenols, exhibit significant antioxidant and bioactive properties, which are crucial for maintaining health and preventing non-communicable diseases.[228.1] The effectiveness of these antioxidants is influenced by their chemical structures, interactions with other food compounds, and their concentrations at the site of reaction with ROS.[220.1] Recent studies underscore the importance of a balanced incorporation of dietary antioxidants to enhance the overall antioxidant defense system and improve health outcomes.[228.1] Research has highlighted the complex relationship between oxidative stress and various diseases, emphasizing the mechanisms through which oxidative stress can contribute to pathology and the role of antioxidant defenses in mitigating these effects.[221.1] Despite extensive research into the potential benefits of antioxidants in the context of aging, cancer, cardiovascular diseases, and neurodegenerative diseases, there remains a lack of clear clinical evidence supporting the efficacy of antioxidant supplementation.[227.1] While experimental studies have shown promising results, the translation of these findings into clinical practice has not demonstrated definitive benefits, indicating a need for further investigation into the effectiveness of antioxidant therapies.[227.1] Recent findings emphasize the importance of dietary antioxidants in managing oxidative stress-related diseases. Phytochemicals found in fruits, vegetables, and medicinal plants have been shown to possess significant antioxidant properties, contributing to the prevention and treatment of chronic diseases.[228.1] Moreover, the incorporation of these antioxidants into a balanced diet is essential for maintaining health and preventing non-communicable diseases.[228.1]In this section:
Challenges In Antioxidant Therapy
Limitations of Current Antioxidant Strategies
Current antioxidant strategies face significant limitations that impact their clinical efficacy. Clinical trial results have shown that antioxidants, such as selenium, vitamin C, vitamin E, and vitamin A, yield inconsistent outcomes, often benefiting only specific subgroups of the population.[270.1] This inconsistency can be attributed to several factors, including differences in intervention age, enrollment criteria, genetic variation, and the choice and dosage of antioxidants administered during trials.[268.1] Despite initial optimism regarding the potential of antioxidants observed in preclinical studies, there has been a notable failure in clinical translation, underscoring the need for a greater understanding of the molecular events associated with these compounds to enhance treatment development and improve chemoprevention strategies.[266.1] The clinical application of antioxidant therapies faces significant challenges due to various factors related to free radical generation and the specific types of therapies employed. The intricate network associated with oxidative stress complicates the effectiveness of these treatments, as antioxidants may not adequately neutralize free radicals, leading to a state of oxidative stress that is linked to a wide range of severe and debilitating disorders, including neurodegenerative diseases.[266.1] Furthermore, the efficacy of antioxidant therapies, such as selenium, vitamin C, vitamin E, and vitamin A, has been notably inconsistent in clinical trials, highlighting the need for a more targeted and specific approach to antioxidant therapy.[266.1] Collectively, these factors underscore the observed shortcomings in the application of antioxidant therapies within clinical settings.[266.1] Additionally, the bioavailability of certain antioxidants, such as polyphenols, poses a challenge in achieving effective therapeutic concentrations in patients. This issue, combined with the complexity of disease pathophysiology and patient compliance, complicates the design and execution of randomized clinical trials.[267.1]Future Directions in Antioxidant Research
The integration of nanotechnology into antioxidant therapy represents a promising avenue for addressing the limitations of conventional antioxidant compounds. Traditional antioxidants often face challenges such as non-specific distribution, high renal clearance, and low delivery efficiency, which can hinder their therapeutic efficacy.[283.1] However, advancements in nanotechnology have the potential to overcome these obstacles, leading to the development of novel classes of nanoantioxidants that exhibit potent radical scavenging and quenching capacities.[281.1] These innovations could significantly enhance the effectiveness of antioxidant therapies in clinical settings. Despite the potential benefits, the efficacy of existing antioxidant therapies, including well-known compounds like selenium, vitamin C, and vitamin E, has been inconsistent in clinical trials.[282.1] This inconsistency may stem from various factors, including the nature of free radical generation and the specific type of therapy employed.[282.1] Therefore, future research must focus on understanding the mechanisms of oxidative stress and how they can be effectively integrated into the design of clinical trials for antioxidant therapies. By elucidating the pathways through which oxidative stress contributes to disease, researchers can develop more targeted and reliable therapeutic strategies.[286.1] Future directions in antioxidant research highlight the significance of personalized nutrition in optimizing antioxidant therapy. The understanding of how nutritional interventions and diet interact with oxidative stress and inflammation is an area of high importance, suggesting that tailored dietary strategies could play a crucial role in preventing and managing oxidative stress-related diseases.[288.1] Furthermore, it is essential to consider individual factors, such as age and health status, when designing these interventions, particularly in vulnerable populations like premature infants, where restoring redox homeostasis is critical.[287.1] This personalized approach underscores the need for further exploration into the interplay between diet, oxidative stress, and inflammation to enhance the effectiveness of antioxidant strategies.[288.1]In this section:
Clinical TrialGenetic VariationClinical TranslationTreatment DevelopmentChemoprevention Strategies
Interplay With Other Biological Systems
Gut Microbiota and Antioxidants
The gut microbiota interacts with dietary antioxidants, such as vitamins C and E, to enhance their effectiveness in combating oxidative stress. These antioxidants work together to reduce the effects of oxidative stress, which is a normal process that occurs in the body. Excellent sources of vitamin E include nuts (such as almonds and hazelnuts), seeds (like sunflower seeds), avocadoes, spinach, and olive oil, which can contribute to improved antioxidant capacity.[316.1] Moreover, polyphenol-rich supplements have been shown to reduce oxidative stress and inflammation, which is particularly beneficial for individuals in high-stress environments, such as healthcare professionals.[317.1] Foods rich in antioxidants, including cherries, berries, sweet potatoes, spinach, and dark chocolate, not only support muscle recovery but also help combat oxidative stress that could lead to inflammation and other health issues.[318.1] Artichokes, which are abundant in antioxidants like polyphenols, quercetin, and rutin, also contribute to cellular protection against oxidative damage.[319.1] Additionally, dietary antioxidants such as selenium and β-carotene have been recognized for their ability to counteract oxidative damage to biomolecules, suggesting that increased intake of these compounds may offer protective benefits.[320.1] Incorporating lesser-known antioxidant-rich foods into the diet can significantly enhance its overall antioxidant profile. Maqui berries, native to South America, particularly Argentina and Chile, are recognized for their high antioxidant content and numerous health benefits.[216.1] Similarly, camu camu is noted not only for its immune-boosting properties but also for containing antioxidants such as ellagic acid and catechins, which help protect cells from oxidative damage.[217.1] Additionally, chaga mushrooms are distinguished by their exceptionally high antioxidant content, particularly in the form of polyphenols, beta-glucans, and melanin. These compounds work synergistically to combat oxidative stress, support immune function, and promote overall longevity.[218.1]Redox Signaling and Cellular Responses
Oxidative stress is defined as an imbalance between oxidants and antioxidants, favoring oxidants, which disrupts redox signaling and can lead to molecular damage across various biological systems.[300.1] This imbalance is implicated in numerous pathophysiological conditions, including cancer, cardiovascular diseases, and neurodegenerative disorders, highlighting the critical role of oxidative stress in cellular responses.[299.1] The concept of oxidative stress has gained acceptance in both basic and applied biology, with significant advancements in understanding the molecular mechanisms involved, particularly the role of reactive oxygen species (ROS) in modulating cellular functions.[301.1] The response to oxidative stress is intricately regulated by redox-sensitive signaling pathways. For instance, the Nrf2/Keap1 system is a key regulator that responds to mild oxidative stress by upregulating antioxidant enzymes, thereby enhancing the cellular antioxidant defense mechanisms.[301.1] This system operates through the oxidation or electrophilic modification of specific cysteine residues in the Keap1 protein, which serves as a sensor for oxidative stress.[301.1] Such regulatory mechanisms are essential for maintaining cellular redox homeostasis and preventing oxidative damage. Moreover, oxidative stress markers serve as valuable tools for assessing the biological redox status and the progression of diseases. These markers can indicate oxidative damage to biomolecules, including proteins, lipids, and DNA, thereby providing insights into the health-enhancing effects of antioxidants.[195.1] However, the application of these biomarkers in clinical settings requires careful validation due to the variability of oxidative stress levels across different diseases.[303.1] For example, in chronic obstructive pulmonary disease (COPD), oxidative stress is recognized as a significant mechanism in disease development, underscoring the importance of identifying oxidative stress-related biomarkers for improving diagnosis and treatment.[304.1]In this section:
References
[1] Oxidative Stress - an overview | ScienceDirect Topics — Oxidative stress. Oxidative stress is defined as the stress occurring when the physiological balance between pro-oxidants and antioxidants tips in favour of pro-oxidants, eliciting molecular and therefore cellular damage due to oxidation. Recent studies 8,26 have provided sufficient evidence to show that oxidative stress plays an important role in EBI. . The most important producers of free
[3] RONS and Oxidative Stress: An Overview of Basic Concepts - MDPI — Oxidative stress (OS) has greatly interested the research community in understanding damaging processes occurring in cells. OS is triggered by an imbalance between reactive oxygen species (ROS) production and their elimination by the antioxidant system; however, ROS function as second messengers under physiological conditions. ROS are produced from endogenous and exogenous sources. Endogenous
[4] Oxidative stress: an overview of past research and future insights — Molecularswitches;oxidative stress;proteomics;redox biology 1. Introduction The concept of oxidative stress (OS) first emerged in 1985 in reference to an imbalance between the oxidants which attack the cell and the antioxidants responsible for defending it, leading to the disrup-tion in redox signaling and control, and thus caus-
[5] An Overview of Oxidative Stress, Neuroinflammation, and ... - PubMed — Oxidative stress has been linked with a variety of diseases, being involved in the debut and/or progress of several neurodegenerative disorders. This review intends to summarize some of the findings that correlate the overproduction of reactive oxygen species with the pathophysiology of Alzheimer's disease, Parkinson's disease, Huntington's
[6] Oxidative Stress: Concept and Some Practical Aspects - PMC — Keywords: oxidative stress, antioxidants, biomarkers. 1. Introduction "Oxidative stress" is a global concept in redox biology and medicine. Since its introduction in 1985 , it has attracted widespread interest and also some critical comments , and it is covered in detail in a textbook (pp. 199-283). The literature on oxidative stress is
[8] Oxidative Stress and Tissue Repair: Mechanism, Biomarkers, and ... — The balance between ROS production and antioxidant defense is important for efficient tissue repair in organs such as the skin, liver, lungs, kidneys, heart, and testes [4-6]. When the tissue is damaged by reactive species, it is common to observe lipid, protein, and DNA damage, leading to oxidative stress that disables tissue repair .
[9] Oxidative Stress to Promote Cell Death or Survival - PMC — Oxidative stress is one of the mechanisms through which cells respond by activating pathways of cell survival or programmed cell death. The initial response of the cell to a stressful stimulus is activated for helping the cell to defend itself and respond positively to the insult. If the insult is very harmful and unresolved, it is the
[11] Molecular mechanisms underlying mitochondrial damage, endoplasmic ... — Environmental pollutants have been shown to induce oxidative stress, and many of them alter the redox balance, leading to ROS generation and cellular damage. 83, 84 Oxidative stress can induce an inflammatory response, which may lead to apoptosis or cell death. At the early stages of exposure, oxidative stress, as a cellular response to
[12] Environmental Oxidant Pollutant Effects on Biologic Systems | A Focus ... — The environmental oxidant pollutants, including ozone (O 3), oxides of nitrogen, and particulates with chemically active surfaces (e.g., containing redox-cycling substances), represent an important source of oxidative stress to terrestrial plants and invertebrates and to vertebrate organisms including humans.
[13] Oxidative Stress and Air Pollution Exposure - PMC — The general consensus does indicate that the mechanism of air pollution-induced health effects involves an inflammation-related cascade and oxidation stress both in lung, vascular, and heart tissue [14–19]. reported that 1-nitropyrene, one of the most abundant nitro-PAHs in diesel exhausts, induces DNA damage by ROS formation in human endothelial cells, and this effect was mainly mediated by metabolites mainly generating by reduction of nitro group, as it has been previously reported by Topinka et al. Several studies have demonstrated that air pollution particles induce inflammatory mediator release and oxidative stress in lung epithelial cells and alveolar macrophages.
[14] Oxidative stress pathways of air pollution mediated toxicity: Recent ... — Air pollution is the leading environmental risk factor in the world today. Particulate matter <2.5 μm (PM 2.5) is the most commonly implicated constituent that causes a disproportionate number of global deaths and contributes significantly to global disability.The global burden of disease study report indicated that ambient outdoor air pollution, particularly PM 2.5, was the fifth leading
[15] Environmental factors and unhealthy lifestyle influence oxidative ... — Exposure to environmental or pathological agents such as atmospheric pollutants, cigarette smoking, ultraviolet rays, radiation, and toxic chemicals results in an imbalance between the pro-oxidants and antioxidants, which leads to oxidative stress (Videla 2009).Pro-oxidant antioxidant balance in the cell is shifted towards the pro-oxidants if the production of oxygen species is increased
[16] Oxidative Stress: Causes, Symptoms & Treatment - Cleveland Clinic — Oxidative stress is an imbalance of free radicals and antioxidants in your body that leads to cell damage. Toxins like pollution and cigarette smoke can cause oxidative stress, while foods rich in antioxidants can help reduce it. Oxidative stress is an imbalance between two different types of molecules in your body: free radicals and antioxidants. Free radicals can harm you if there are too many in your body (oxidative stress). Free radicals and antioxidants are two different types of molecules, or chemical compounds, that play a role in how your body works. Extensive sun exposure, stress and smoking can cause your body to make more free radicals than it needs. Anything that raises the number of free radicals in your body to unhealthy levels can cause oxidative stress.
[17] Oxidative stress: A target to treat Alzheimer's disease and stroke — Oxidative stress is a common factor responsible for the onset and progression of several prominent diseases of CNS such as stroke and Alzheimer's disease (AD). Oxidative stress continues to remain a key therapeutic target for neurological diseases due to the unique vulnerability of the brain to oxidative damage and knowledge that high levels of
[18] Mechanism of Oxidative Stress and Synapse Dysfunction in the ... — We suggest that oxidative stress mediated through NMDAR and their interaction with other molecules might be a driving force for tau hyperphosphorylation and synapse dysfunction. Thus, understanding the oxidative stress mechanism and degenerating synapses is crucial for the development of therapeutic strategies designed to prevent AD pathogenesis.
[19] Role of oxidative stress in neurodegenerative disorders: a review of ... — This review aims to examine some intracellular antioxidant mechanisms that reduce reactive oxygen species (ROS) and the effects of oxidative stress (OS) in the CNS and explores deficiencies of these mechanisms as a cause of disease in neurodegenerative disorders (ND), focusing particularly on Alzheimer's disease, Parkinson's disease and
[20] Oxidative stress and mitochondrial impairment: Key drivers in ... — Recent evidence has underscored the critical roles of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases (Bai et al., 2022; Catanesi et al., 2020; Keller et al., 2019a). Consequently, mitochondrial dysfunction in neurons leads to energy metabolism disorders and cell death, resulting in CNS dysfunction, which may be a crucial trigger for neurodegenerative diseases (Cozzolino and Carrì, 2012a; Pekkurnaz and Wang, 2022; Rocha et al., 2018). Emerging evidence suggests that strategies aimed at alleviating mitochondrial dysfunction and oxidative stress by enhancing mitochondrial biogenesis, improving mitochondrial dynamics and function, and boosting antioxidant defenses may hold great promise for the treatment of neurodegenerative diseases (Fields et al., 2023; Scarian et al., 2024; Tian et al., 2009).
[46] The Concept of Oxidative Stress After 30 Years | SpringerLink — Oxidative stress is an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage (Sies H, Jones DP, Oxidative stress. ... This discovery opened an exciting field on membrane transport of hydrogen peroxide by peroxiporins [24
[47] Oxidative stress concept updated: Definitions, classifications, and ... — Sies inspired many investigations in the field of oxidative stress such that, at present, the oxidative stress concept is well accepted and extensively used in both basic and applied fields of biology and medicine (Storey, 1996; Freire et al., 2011; Jones and Sies, 2015; Cadenas et al., 2016; Salim, 2017; Islam, 2017; Garaschuk et al., 2018; Lushchak, 2021). Since the first definition of oxidative stress (Sies, 1985), molecular mechanisms of ROS-induced up-regulation of antioxidant enzymes have been discovered. In animals, the response to mild oxidative stress is coordinated by the ROS-sensitive Nrf2/Keap1 system that is based on the oxidation or electrophylic modification of cysteine residue/s of the sensor protein Keap1 (Nguyen et al., 2009; Lushchak, 2012, 2014; Baxter and Hardingham, 2016; Sies, 2017).
[48] Modulation of oxidative stress as an anticancer strategy — The regulation of oxidative stress is an important factor in both tumour development and responses to anticancer therapies. ... This paper reports the discovery that hyperactivation of the PI3K
[50] On the history of oxidative stress: Concept and some ... - ScienceDirect — Oxidative stress as a concept in redox biology and medicine has witnessed fulminant development of the past 30-odd years. It is a global concept, defined as "an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage" (Sies H, Jones DP: Oxidative stress.
[51] Oxidative Stress: Eustress and Distress in Redox Homeostasis — The basic principle of stress and stress responses was originated by Selye in 1936, 1 and the concept of oxidative stress and oxidative stress responses was formulated in 1985 in the book entitled "Oxidative Stress." 2 Since then, there has been lively development within the wider field of redox biology and medicine. "Oxidative stress" is a global concept, which by definition does not
[52] Strategies to Counteract Oxidative Stress and Inflammation in Chronic ... — Oxidative stress and inflammation are recognized as pivotal contributors and common features of several chronic degenerative diseases, including cancer, metabolic syndrome, type 2 diabetes, cardiovascular diseases and neurodegenerative disorders, affecting a high percentage of the population .Oxidative stress is characterized by an imbalance between the production of reactive oxygen
[96] Oxidative Stress: Concept and Some Practical Aspects - PMC — Oxidative stress is defined as “an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage”. Multiple biomarkers of damage due to oxidative stress have been identified for different molecular classes (protein, lipid, carbohydrate, and DNA), and the current state of practical aspects in health and disease is delineated. Keywords: oxidative stress, antioxidants, biomarkers The complement of antioxidant enzymes is subject to regulation by redox master switches as part of the oxidative stress response (see Ref. Redox systems analysis of antioxidant networks will help to further understand the interplay of nutrition and oxidative stress . 5.Sies H., Berndt C., Jones D.P. Oxidative stress. 44.Dennis K.K., Go Y.M., Jones D.P. Redox systems biology of nutrition and oxidative stress.
[97] Frontiers | Oxidative stress: fundamentals and advances in ... — Introduction "Oxidative stress" is a term that was first coined in 1985 by the German physician, Helmut Sies as an imbalance between the production of oxidants and antioxidant defenses that may result in damage to biological systems (Forman and Zhang, 2021).Since then, the phenomenon has been extensively studied, as it has been implicated in a wide range of diseases, including cancer
[101] Cells | Special Issue : Recent Advances of Oxidative Stress and ... - MDPI — The purpose of this Special Issue is to highlight the research advances regarding the interactions between oxidative stress and inflammation in diabetes. Our goal is to provide research papers and reviews related to endogenous and external antioxidant defense systems and to present modern therapeutic strategies in the treatment of DM that aim
[102] New Insights on Oxidative Stress and Diabetic Complications May Lead to ... — Recent basic and clinical studies have uncovered new insights into the role of oxidative stress in diabetic complications, suggesting a different and innovative approach to a possible "causal" antioxidant therapy. The aim of this review is to give an update on this topic.
[103] Oxidative Stress: Pathogenetic Role in Diabetes Mellitus and Its ... — Modern therapeutic strategies in the treatment of diabetes mellitus are aimed at developing new methods of personalized antioxidant therapy, including ROS sources targeting combined with new ways of antioxidant delivery. Keywords: antioxidants; diabetes mellitus; experiment; oxidative stress; patients.
[104] Oxidative Stress and Cancer Therapy: Controlling Cancer Cells Using ... — Oxidative stress, primarily driven by ROS, plays a significant role in cancer development and progression and contributes to other pathological conditions, such as diabetes, metabolic disorders, and atherosclerosis, which amplify these harmful effects .
[105] Oxidative Stress in Health and Disease - PMC - PubMed Central (PMC) — This review addresses the role of oxidative stress in the pathogenesis of AGE-related chronic diseases, including diabetes and neurological disorders, and recent progress in the development of therapeutics based on antioxidants, AGE breakers and RAGE inhibitors. Keywords: oxidative stress, Alzheimer’s disease, diabetes, reactive oxygen species, reactive nitrogen species, 4-hydroxy-trans-2-nonenal (HNE), lipid peroxidation, nanozymes, receptors for advanced glycation end products (RAGE) Although ROS and RNS act as signaling molecules under physiological concentrations, under oxidative conditions, excessive amounts of ROS and RNS exert cellular damage through their deleterious reactions with proteins, lipids, and DNA, thereby leading to the pathogenesis of various oxidative stress-related diseases, including diabetes, obesity, and neurological diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) .
[135] Reactive oxygen species, toxicity, oxidative stress, and antioxidants ... — A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or "good stress" and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulation of signal transduction pathways such as
[136] Oxidative Stress: Harms and Benefits for Human Health — ROS can play, and in fact they do it, several physiological roles (i.e., cell signaling), and they are normally generated as by-products of oxygen metabolism; despite this, environmental stressors (i.e., UV, ionizing radiations, pollutants, and heavy metals) and xenobiotics (i.e., antiblastic drugs) contribute to greatly increase ROS production, therefore causing the imbalance that leads to cell and tissue damage (oxidative stress). Immune cell activation, inflammation, ischemia, infection, cancer, excessive exercise, mental stress, and aging are all responsible for endogenous free radical production. M. Aesculetin-induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway in human cervical cancer cells. J. The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention. K. Hydroxytyrosol induces apoptosis in human colon cancer cells through ROS generation.
[137] Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional ... — Oxidative stress is a physiological condition characterized by an imbalance between the production of ROS and the ability of cells to detoxify them . It plays a significant role in the disruption of normal cellular function and can lead to inflammation, tissue injury and organ dysfunction.
[139] Reactive Oxygen Species: the Dual Role in Physiological and ... — Additionally, there is a growing body of evidence supporting the role of ROS in various pathological states. The binary nature of ROS with their profitable and injurious characteristics indicates the complexities of their specific roles at a biological compartment and the difficulties in establishing convenient intervention procedures to treat
[142] Targeting oxidative stress in disease: promise and limitations of ... — Targeting oxidative stress in disease: promise and limitations of antioxidant therapy | Nature Reviews Drug Discovery Here, we review the relationships between oxidative stress, redox signalling and disease, the mechanisms through which oxidative stress can contribute to pathology, how antioxidant defences work, what limits their effectiveness and how antioxidant defences can be increased through physiological signalling, dietary components and potential pharmaceutical intervention. This article examines the links between oxidative stress and type 2 diabetes mellitus. T., May, J. Am. J. Am. J. Am. J. Can. J. This article examines the role of oxidative stress in Alzheimer disease. Am. J. K. Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene.
[144] Oxidative stress and inflammation in the pathogenesis of neurological ... — Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications - ScienceDirect Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications Oxidative stress, an imbalance between the body's natural defense mechanisms and the generation of reactive oxygen species, is crucial in developing neurological disorders. Several neurological disorders, including Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, multiple sclerosis, and ischemic stroke, are associated with oxidative stress. Oxidative stress triggers a catastrophic cascade: mitochondrial dysfunction, neuronal death, neuroinflammation, and neurodegeneration, leading to devastating neurodegenerative diseases, necessitating advanced therapies to halt this destructive process. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. For all open access content, the Creative Commons licensing terms apply.
[145] Free radicals and their impact on health and antioxidant defenses: a ... — While free radicals are essential for certain physiological processes, such as cell signaling and immune defense, their overproduction can disrupt the delicate balance between oxidants and antioxidants, leading to oxidative stress. Additionally, we explore natural compounds and extracts studied for their antioxidant properties, offering potential therapeutic avenues for managing free radical-induced damage. Free radicals cause oxidative stress, which contributes to the development of chronic diseases. Antioxidants play a key role in neutralizing free radicals and mitigating oxidative stress. Research into these natural antioxidants offers promising avenues for preventive and therapeutic strategies against oxidative stress-related diseases . Free radicals induce cellular damage through lipid peroxidation, protein oxidation, and DNA damage, contributing to various diseases.
[173] Signaling Functions of Reactive Oxygen Species - PMC — Abstract. We review signaling by reactive oxygen species, which is emerging as a major physiological process. However, among the reactive oxygen species, H 2 O 2 best fulfills the requirements of being a second messenger. Its enzymatic production and degradation, along with the requirements for the oxidation of thiols by H 2 O 2, provide the specificity for time and place that are required in
[175] The Hippo Signaling Pathway, Reactive Oxygen Species ... - PubMed — The Hippo signaling pathway is recognized for its significant role in cell differentiation, proliferation, survival, and tissue regeneration. Recently, the Hippo signaling pathway was also found to be associated with oxidative stress and reactive oxygen species (ROS) regulation, which are important in the regulation of cell survival.
[176] Beneficial and Detrimental Effects of Reactive Oxygen Species on ... — Finally, deletion of Prx1 in mice increases ROS production and oxidative damage and decreases lifespan (Neumann et al., 2003; Rani et al., 2012). In mice, a 50% reduction in expression of the mitochondrial thioredoxin gene, Trx2, increases ROS production and oxidative damage and slightly reduces lifespan (Pérez et al., 2008). In yeast, it has been shown that disruption of genes encoding catalase (cta1 or ctt1) increases the levels of intracellular ROS (hydrogen peroxide) and increases oxidative damage (protein carbonylation), but also increases lifespan (Mesquita et al., 2010). In mice, it has been shown that a heterozygous mutation in the mouse homolog of clk-1, Mclk1, results in increased levels of mitochondrial ROS, increased levels of oxidative damage and increased lifespan (Liu et al., 2005).
[177] ROS Function in Redox Signaling and Oxidative Stress - PMC — Additionally, the signaling pathways responsive to hydrogen peroxide are localized to the sources of ROS generation, allowing activation of these pathways despite the high overall antioxidant activity in cancer cells that protects against oxidative stress-induced cell death. In summary, we support a model in which tumorigenic cells generate high levels of ROS to activate proximal signaling pathways that promote proliferation, survival and metabolic adaptation (i.e. redox biology). At the same time, cancer cells maintain a high level of antioxidant activity to prevent buildup of ROS to levels that could induce cell death (i.e. oxidative stress) (Figure 2). By contrast, high levels of ROS impair stem cell function by activating signaling pathways that limit self-renewal, but do not necessarily cause cellular damage.
[179] Oxidative Stress - an overview | ScienceDirect Topics — Oxidative stress is an unavoidable consequence of life in an oxygen-rich atmosphere. In living organisms, it is defined as the disturbance of the delicate balance between the oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or to direct molecular damage (Fig. 1.1) .Whereas an excessive amount of oxidative stress may cause damage
[180] Oxidative stress - Wikipedia — 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. Some of the less reactive of these species (such as superoxide) can be converted by oxidoreduction reactions with transition metals or other redox cycling compounds (including quinones) into more aggressive radical species that can cause extensive cellular damage. Most long-term effects are caused by damage to DNA. DNA damage induced by ionizing radiation is similar to oxidative stress, and these lesions have been implicated in aging and cancer.
[181] Oxidative Stress: Concept and Some Practical Aspects - PMC — Oxidative stress is defined as “an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage”. Multiple biomarkers of damage due to oxidative stress have been identified for different molecular classes (protein, lipid, carbohydrate, and DNA), and the current state of practical aspects in health and disease is delineated. Keywords: oxidative stress, antioxidants, biomarkers The complement of antioxidant enzymes is subject to regulation by redox master switches as part of the oxidative stress response (see Ref. Redox systems analysis of antioxidant networks will help to further understand the interplay of nutrition and oxidative stress . 5.Sies H., Berndt C., Jones D.P. Oxidative stress. 44.Dennis K.K., Go Y.M., Jones D.P. Redox systems biology of nutrition and oxidative stress.
[182] Oxidative Stress in Health and Disease - PubMed — Oxidative stress is also implicated in cardiovascular disease and cancer. Exacerbated oxidative stress leads to the accelerated formation of advanced glycation end products (AGEs), a complex mixture of crosslinked proteins and protein modifications.
[183] (PDF) Oxidative Stress in Health and Disease - ResearchGate — This review addresses the role of oxidative stress in the pathogenesis of AGE-related chronic diseases, including diabetes and neurological disorders, and recent progress in the development of
[184] Oxidative Stress in Health and Disease - PMC — This review addresses the role of oxidative stress in the pathogenesis of AGE-related chronic diseases, including diabetes and neurological disorders, and recent progress in the development of therapeutics based on antioxidants, AGE breakers and RAGE inhibitors. Keywords: oxidative stress, Alzheimer’s disease, diabetes, reactive oxygen species, reactive nitrogen species, 4-hydroxy-trans-2-nonenal (HNE), lipid peroxidation, nanozymes, receptors for advanced glycation end products (RAGE) Although ROS and RNS act as signaling molecules under physiological concentrations, under oxidative conditions, excessive amounts of ROS and RNS exert cellular damage through their deleterious reactions with proteins, lipids, and DNA, thereby leading to the pathogenesis of various oxidative stress-related diseases, including diabetes, obesity, and neurological diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) .
[186] Interplay of oxidative stress, cellular communication and signaling ... — Oxidative stress, characterized by the production of reactive oxygen species (ROS) within cells, plays a critical role in the development of cancer by affecting genomic stability and signaling pathways within the cellular microenvironment. Nitroxide derivatives (e.g., Tempol, Tempone) - generate ROS to induce oxidative stress in cancer cells. These actions lead to the re-expression of genes that encode for antioxidants like glutathione and superoxide dismutases (SOD), thus altering the cellular redox state and making cancer cells more susceptible to oxidative stress-induced apoptosis . By inhibiting this enzyme, the cellular levels of ROS are reduced, which can inhibit the oxidative stress-induced signaling pathways that promote cancer cell proliferation . ROS modulation affects critical signaling pathways like Keap1-Nrf2, which traditionally regulates oxidative stress, and impacts tumor suppressor genes including p53, BRCA1, BRCA2, and RB1.
[195] (PDF) Approaches and Methods to Measure Oxidative Stress in Clinical ... — tive stress in clinical samples: (1) direct measurement of ROS levels, (2) detection of the resulting oxidative damage to bio- molecules (DNA, lipids, and proteins), and (3) determination
[216] Lesser-Known Berry Varieties: Unlocking Their Antioxidant Power — Uncommon berries with incredible antioxidant qualities 1. Maqui berries. One lesser-known variety that is loaded with diverse beneficial antioxidants is maqui berries. Native to South America, particularly Argentina and Chile, maqui berries possess many health benefits due to their high antioxidant content.
[217] 10 Lesser-Known Super foods for Optimal Health - BeRationally — Unlock the secrets to optimal health with these 10 lesser-known super foods! From nutrient-packed moringa to immune-boosting camu camu, discover how these hidden gems can elevate your well-being. ... In addition to its immune-boosting properties, camu camu contains antioxidants like ellagic acid and catechins, which help protect cells from
[218] 32 Lesser-Known Superfoods That Pack More Nutrients Than Kale — Unlike common culinary mushrooms, chaga is prized for its exceptionally high antioxidant content, particularly in the form of polyphenols, beta-glucans, and melanin, which work together to combat oxidative stress, support immune function, and promote overall longevity. One of chaga's standout properties is its ability to stimulate immune
[220] Biochemistry of Antioxidants: Mechanisms and Pharmaceutical ... — Supplementation of exogenous natural antioxidants in the diet to improve the endogenous antioxidant defense system of the body is a strategy to reduce the undesirable effects of RONs. However, screening for natural bioantioxidants with suitable pharmacological properties has turned out to be challenging because the activity of natural antioxidants (or natural extracts) in inhibiting oxidative stress depends, among other factors, on their chemical structures, bond dissociation enthalpies and redox potentials and on their effective concentrations at the reaction site with RONs . Scavenging of peroxyl radicals (ROO•) or repairing of the damaged target molecules can be achieved by enhancing the levels of endogenous antioxidants and/or addition of exogenous antioxidants such as (poly)phenolic compounds or ArO-H (reaction 5 in Figure 1).
[221] Targeting oxidative stress in disease: promise and limitations of ... — Targeting oxidative stress in disease: promise and limitations of antioxidant therapy | Nature Reviews Drug Discovery Here, we review the relationships between oxidative stress, redox signalling and disease, the mechanisms through which oxidative stress can contribute to pathology, how antioxidant defences work, what limits their effectiveness and how antioxidant defences can be increased through physiological signalling, dietary components and potential pharmaceutical intervention. This article examines the links between oxidative stress and type 2 diabetes mellitus. T., May, J. Am. J. Am. J. Am. J. Can. J. This article examines the role of oxidative stress in Alzheimer disease. Am. J. K. Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene.
[222] Understanding mechanisms of antioxidant action in health and disease — Advertisement View all journals Search Log in Explore content About the journal Publish with us Subscribe Sign up for alerts RSS feed nature nature reviews molecular cell biology review articles article Review Article Published: 15 September 2023 Understanding mechanisms of antioxidant action in health and disease Barry Halliwell ORCID: orcid.org/0000-0002-3560-71231,2 Nature Reviews Molecular Cell Biology volume 25, pages 13–33 (2024)Cite this article 12k Accesses 50 Altmetric Metrics details Subjects Cell signalling Mechanisms of disease Physiology Abstract Several different reactive oxygen species (ROS) are generated in vivo. ROS are counterbalanced by an antioxidant defence network, which functions to modulate ROS levels to allow their physiological roles whilst minimizing the oxidative damage they cause that can contribute to disease development. This Review describes the mechanisms of action of antioxidants synthesized in vivo, antioxidants derived from the human diet and synthetic antioxidants developed as therapeutic agents, with a focus on the gaps in our current knowledge and the approaches needed to close them. The Review also explores the reasons behind the successes and failures of antioxidants in treating or preventing human disease.
[223] Reactive oxygen species, toxicity, oxidative stress, and antioxidants ... — Attention is focused on the chemistry of ROS and RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl radicals, nitric oxide, peroxynitrite), and their role in oxidative damage of DNA, proteins, and membrane lipids. Oxidative stress, characterized by a shifted equilibrium between the formation and elimination of free radicals toward the formation, is a common denominator of the pathogenesis of chronic diseases and aging (Harman 1956; Valko et al. Under the conditions of disturbed redox metal homeostasis (e.g. Alzheimer’s diseases and some cancers), free (unbound) metal ions can catalyze heterolytic cleavage of hydrogen peroxide (formed by the SOD-catalyzed dismutation reaction), resulting in the formation of hydroxyl radicals (·OH) and OH−.
[227] Effect of Antioxidant Therapy on Oxidative Stress in Vivo — Over the last few decades, many efforts have been put into fields that explore the potential benefits of antioxidants, especially with regards to aging, cancer, cardiovascular diseases, and neurodegenerative diseases .However, despite the positive results in experimental studies, there is no clear evidence of clinical benefit of antioxidant supplementation.
[228] Oxidative Stress: The Role of Antioxidant Phytochemicals in the ... — Phytochemicals, present in a wide range of foods and medicinal plants, play a pivotal role in preventing and treating chronic diseases induced by oxidative stress by working as antioxidants. The reported structural composition and interactions with other food compounds play a pivotal role in influencing the activities and bioavailability of polyphenols, thereby causing diverse biological effects. Recent studies highlight the significance of a balanced incorporation of polyphenols into diets, emphasizing their high antioxidant and bioactive properties essential for maintaining good health and preventing prevalent human NCDs. Several studies have elucidated the antioxidant and anti-inflammatory effects of polyphenols derived from various sources in diverse in vitro and in vivo experimental settings.
[234] Antioxidants Explained In Simple Terms - Klarity Health Library — Higher intakes of plant antioxidants are associated with a lower risk of cancers, heart disease, and stroke. The best way to increase your intake is to eat a variety of antioxidant-rich plant foods. A comprehensive list of more than 3,100 foods, beverages, spices, herbs and supplements and their total antioxidant content can be found here.
[240] Understanding mechanisms of antioxidant action in health and disease — Advertisement View all journals Search Log in Explore content About the journal Publish with us Subscribe Sign up for alerts RSS feed nature nature reviews molecular cell biology review articles article Review Article Published: 15 September 2023 Understanding mechanisms of antioxidant action in health and disease Barry Halliwell ORCID: orcid.org/0000-0002-3560-71231,2 Nature Reviews Molecular Cell Biology volume 25, pages 13–33 (2024)Cite this article 12k Accesses 50 Altmetric Metrics details Subjects Cell signalling Mechanisms of disease Physiology Abstract Several different reactive oxygen species (ROS) are generated in vivo. ROS are counterbalanced by an antioxidant defence network, which functions to modulate ROS levels to allow their physiological roles whilst minimizing the oxidative damage they cause that can contribute to disease development. This Review describes the mechanisms of action of antioxidants synthesized in vivo, antioxidants derived from the human diet and synthetic antioxidants developed as therapeutic agents, with a focus on the gaps in our current knowledge and the approaches needed to close them. The Review also explores the reasons behind the successes and failures of antioxidants in treating or preventing human disease.
[241] Reactive oxygen species and antioxidant vitamins: mechanisms of action — Reactive oxygen species and antioxidant vitamins: mechanisms of action - PubMed Search: Search Your saved search Name of saved search: Reactive oxygen species and antioxidant vitamins: mechanisms of action Reactive oxygen species and antioxidant vitamins: mechanisms of action The mechanisms of lipid peroxidation and antioxidant protection are explained using a specific example, viz., oxidative modification of human low density lipoprotein and its prevention by vitamin C, vitamin E, and beta-carotene. Oxidative modification and antioxidant protection of human low density lipoprotein at high and low oxygen partial pressures. Antioxidant vitamins and low-density-lipoprotein oxidation. Antioxidant effect of ethanol toward in vitro peroxidation of human low-density lipoproteins initiated by oxygen free radicals. Vitamins E and C, beta-carotene, and other carotenoids as antioxidants.
[242] The mechanism(s) of action of antioxidants: From scavenging reactive ... — The mechanism(s) of action of antioxidants: From scavenging reactive oxygen/nitrogen species to redox signaling and the generation of bioactive secondary metabolites - PubMed The mechanism(s) of action of antioxidants: From scavenging reactive oxygen/nitrogen species to redox signaling and the generation of bioactive secondary metabolites The mechanism(s) of action of antioxidants: From scavenging reactive oxygen/nitrogen species to redox signaling and the generation of bioactive secondary metabolites This implies that exploring the free radical scavenging-related metabolite fingerprint of each antioxidant molecule, collectively defined here as the scavengome, will lead to a deeper understanding of the bioactivity of these compounds. Keywords: antioxidant mechanism of action; bioactive metabolite; free radical scavenging; oxidative stress; scavengome.
[243] Biochemistry of Antioxidants: Mechanisms and Pharmaceutical ... — Supplementation of exogenous natural antioxidants in the diet to improve the endogenous antioxidant defense system of the body is a strategy to reduce the undesirable effects of RONs. However, screening for natural bioantioxidants with suitable pharmacological properties has turned out to be challenging because the activity of natural antioxidants (or natural extracts) in inhibiting oxidative stress depends, among other factors, on their chemical structures, bond dissociation enthalpies and redox potentials and on their effective concentrations at the reaction site with RONs . Scavenging of peroxyl radicals (ROO•) or repairing of the damaged target molecules can be achieved by enhancing the levels of endogenous antioxidants and/or addition of exogenous antioxidants such as (poly)phenolic compounds or ArO-H (reaction 5 in Figure 1).
[244] Antioxidants and prevention of chronic disease - PubMed — Oxidative stress has been related to cardiovascular disease, cancer, and other chronic diseases that account for a major portion of deaths today. Antioxidants are compounds that hinder the oxidative processes and thereby delay or prevent oxidative stress.
[256] 8 Foods High in Polyphenols and Why You Need Them - WebMD — Healthy Foods High in Polyphenols Studies show that people who have polyphenol-rich diets — consuming more than 650 milligrams per day — have lower death risks than those who get less than 500 milligrams per day. Berries are low in calories and high in vitamin C, fiber, and polyphenols, making them an easy addition to any diet. Because most vegetables contain polyphenols, getting enough in your diet helps you benefit from these antioxidants’ health effects. We consume teas like black, green, or ginger in smaller amounts, but a cup can still add some polyphenols to your diet. Therapeutic Advances in Chronic Disease: “Evidence for a protective effect of polyphenols-containing foods on cardiovascular health: an update for clinicians.”
[257] 19 Foods High in Antioxidants to Eat More Often | livestrong — Red beans contain polyphenols, plant substances with potent antioxidant properties, per a November 2017 study in the International Journal of Molecular Sciences. Although the USDA researchers measured the antioxidant capacity of dried kidney beans, you'll still get plenty of antioxidants and other perks from cooked kidney beans: A 1/2 cup of cooked red kidney beans contains 18 percent of the DV of manganese (which also has antioxidant properties), 7.7 grams of protein and 6.5 grams of heart-healthy fiber. Red raspberries are rich in antioxidants such as vitamin C and flavonoid compounds, including cyanidin and quercetin, per a June 2012 study in the Journal of Agricultural and Food Chemistry.
[258] What Are Polyphenols? Benefits and Foods - Cleveland Clinic Health ... — But a short list of polyphenol-rich foods includes things like: Apples. Berries. Broccoli. Carrots. Chili peppers. Cumin. Dark chocolate (because cocoa is a major source of polyphenols). Flax
[259] Polyphenols Food List: Seasonings, Berries, and More - Healthline — Cocoa powder was the fourth richest polyphenol food identified, with 3,448 mg polyphenols per 100 g of the powder. It's not a surprise that dark chocolate fell close behind on the list and was
[266] Limitations and Challenges of Antioxidant Therapy - PubMed — Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search: Search Your saved search Name of saved search: If these free radicals are not neutralized by antioxidants, they can lead to a state of oxidative stress, which has been linked to a wide range of severe and debilitating disorders affecting various systems in the human body. However, the efficacy of antioxidant therapies in clinical trials, including selenium, vitamin C, vitamin E, and vitamin A, has been notably inconsistent. Collectively, these factors will be explored in this review article to decipher the observed shortcomings in the application of antioxidant therapies within clinical settings. Keywords: antioxidants; clinical trials; free radicals; oxidative stress; therapy. 2024 Dec 6;14(4):e23.00094. E. Rotimi, et al. https://doi.org/10.3390/molecules28114322.
[267] How We Can Change Clinical Practice Using Antioxidant Molecules? - MDPI — There are, in fact, several factors that need to be considered when will be design and execute a randomized clinical trial. In particular, future clinical trials involving DED patients have to take care of low polyphenols bioavailability, the complexity of the DED pathophysiology and patient's compliance and perception of treatment effectiveness.
[268] Antioxidants for prostate cancer chemoprevention: Challenges and ... — Inconsistencies between preclinical and clinical outcomes There has been a general failure of clinical translation despite the optimism regarding antioxidants in the preclinical setting. We propose that differences in intervention age, enrollment criteria, genetic variation, and the choice and dose of antioxidant are important contributing
[270] Anti-Oxidants as Chemopreventive Agents in Prostate Cancer: A Gap ... — However, the clinical trial results showed that antioxidants have yielded mixed outcomes or benefitted only a subgroup of the population. Conclusion: A greater understanding of the molecular events associated with antioxidants will enhance the development of treatment and could result in better strategies for the chemoprevention of prostate cancer.
[281] Nanoantioxidants: Pioneer Types, Advantages, Limitations, and Future ... — Indeed, nanoscience has provided promising solutions to address the challenges associated with conventional antioxidant compounds and to enable the development of pioneering classes of nanoantioxidants . More interestingly, many categories of nanoantioxidants have potent radical scavenging and quenching capacities that have shown greater
[282] Limitations and Challenges of Antioxidant Therapy - PubMed — However, the efficacy of antioxidant therapies in clinical trials, including selenium, vitamin C, vitamin E, and vitamin A, has been notably inconsistent. This inconsistency can be primarily ascribed to different factors related to the nature of free radical generation, purpose and the specific type of therapy employed, and the intricate
[283] Antioxidant Nanotherapies for the Treatment of Inflammatory Diseases — Various adverse effects of low molecular weight ROS scavengers are mainly due to their non-specific distribution, high renal clearance, and low delivery efficiency. The emergence of nanotechnology has considerably overcome these limitations and inspires the next wave of technological innovation in antioxidant therapy.
[286] Targeting oxidative stress in disease: promise and limitations of ... — Here, we review the relationships between oxidative stress, redox signalling and disease, the mechanisms through which oxidative stress can contribute to pathology, how antioxidant defences work, what limits their effectiveness and how antioxidant defences can be increased through physiological signalling, dietary components and potential pharmaceutical intervention. Here, Forman and Zhang review the roles of oxidative stress and redox signalling in disease, assess antioxidant therapeutic strategies and highlight key limitations that have challenged their clinical application. The first involves the production of reactive species during oxidative stress — particularly •OH, ONOO− and HOCl — that directly oxidize macromolecules, including membrane lipids, structural proteins, enzymes and nucleic acids, leading to aberrant cell function and death.
[287] Sex-Specificity of Oxidative Stress in Newborns Leading to a ... — Abstract Oxidative stress is a critical process that triggers several diseases observed in premature infants. Growing recognition of the detriment of oxidative stress in newborns warrants the use of an antioxidant strategy that is likely to be nutritional in order to restore redox homeostasis. It appears essential to have a personalized approach that will take into account the age of gestation
[288] The Effect of Nutritional Intervention and Diet on Oxidative Stress and ... — The understanding of how nutritional intervention and diet interact with oxidative stress and inflammation is an open field of high importance. Equally relevant is the design of therapeutic strategies based on dietary habits for preventing and managing oxidative stress-related diseases.
[299] Oxidative stress in biological systems and its relation with ... — Oxidative stress in biological systems and its relation with pathophysiological functions: the effect of physical activity on cellular redox homeostasis - PubMed Oxidative stress in biological systems and its relation with pathophysiological functions: the effect of physical activity on cellular redox homeostasis Elevated levels of pro-oxidants and various markers of the oxidative stress and cells and tissues damage linked with pathogenesis of cancer, atherosclerosis, neurodegenerative diseases hypertension, diabetes mellitus, cardiovascular disease, atherosclerosis, reproductive system diseases, and aging were reported. Future studies are needed to clarify the multifaceted effects of reactive oxygen/nitrogen species on cells and tissues and to continue study on the biochemical roles of antioxidants and physical activity in prevention of oxidative stress-related tissue injury. Keywords: Biological systems; human diseases; inflammation; oxidative stress; physical exercise; reactive oxygen/nitrogen species.
[300] Oxidative Stress: Concept and Some Practical Aspects - PMC — Oxidative stress is defined as “an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage”. Multiple biomarkers of damage due to oxidative stress have been identified for different molecular classes (protein, lipid, carbohydrate, and DNA), and the current state of practical aspects in health and disease is delineated. Keywords: oxidative stress, antioxidants, biomarkers The complement of antioxidant enzymes is subject to regulation by redox master switches as part of the oxidative stress response (see Ref. Redox systems analysis of antioxidant networks will help to further understand the interplay of nutrition and oxidative stress . 5.Sies H., Berndt C., Jones D.P. Oxidative stress. 44.Dennis K.K., Go Y.M., Jones D.P. Redox systems biology of nutrition and oxidative stress.
[301] Oxidative stress concept updated: Definitions, classifications, and ... — Sies inspired many investigations in the field of oxidative stress such that, at present, the oxidative stress concept is well accepted and extensively used in both basic and applied fields of biology and medicine (Storey, 1996; Freire et al., 2011; Jones and Sies, 2015; Cadenas et al., 2016; Salim, 2017; Islam, 2017; Garaschuk et al., 2018; Lushchak, 2021). Since the first definition of oxidative stress (Sies, 1985), molecular mechanisms of ROS-induced up-regulation of antioxidant enzymes have been discovered. In animals, the response to mild oxidative stress is coordinated by the ROS-sensitive Nrf2/Keap1 system that is based on the oxidation or electrophylic modification of cysteine residue/s of the sensor protein Keap1 (Nguyen et al., 2009; Lushchak, 2012, 2014; Baxter and Hardingham, 2016; Sies, 2017).
[303] Oxidative Stress and Its Biomarkers in Cardiovascular Diseases — However, the use of these biomarkers in clinical settings still requires validation because of the considerable variation in oxidative stress levels across different diseases . A biomarker is any substance or process that can be measured in the body or its products and can predict the occurrence of a disease or its outcome .
[304] Identification of Oxidative Stress-Associated Biomarkers in Chronic ... — Purpose Chronic obstructive pulmonary disease (COPD) is among the three leading causes of death worldwide, with its prevalence, morbidity, and mortality rates increasing annually. Oxidative stress (OS) is a key mechanism in COPD development, making the identification of OS-related biomarkers beneficial for improving its diagnosis and treatment.
[316] Oxidative Stress: 7 of the Best Nutrients to Protect Your Health! — It works together with other antioxidants like vitamin C to enhance their effectiveness in combating oxidative stress. Excellent sources of vitamin E include nuts (almonds, hazelnuts), seeds (sunflower seeds), avocadoes, spinach, and olive oil. Reduce the Effects of Oxidative Stress. Oxidative stress is a normal process that occurs in the body.
[317] The Role of Dietary Antioxidants, Food Supplements and Functional Foods ... — Clinical studies have shown that polyphenol-rich supplements can reduce oxidative stress and inflammation, supporting the health and energy levels of healthcare professionals working in high-stress environments . | N-Acetyl Cysteine (NAC) | Not found in foods directly; supplement form derived from cysteine, a component of high-protein foods (e.g., poultry and eggs) | Adults (18+): 600–1200 mg/day; Higher Doses (e.g., for lung health): Up to 2400 mg/day under supervision | Men and Women (18–50): For detoxification and antioxidant support; Elderly (50+): Supports cognitive and respiratory health | Precursor to glutathione, scavenges free radicals, replenishes intracellular GSH levels, and reduces oxidative damage in neurodegenerative disorders | Include high-protein foods such as poultry and eggs, which are staples in the Mediterranean diet, for supporting cysteine intake | Antioxidant supplements such as vitamins C and E, omega-3 fatty acids, and CoQ10 have been shown to reduce oxidative damage and improve cognitive function and energy levels.
[318] 8 Dietitian-Loved Antioxidant Foods to Add to Your Rotation - Peloton — The best antioxidant foods include many staples you probably already have in your pantry and fridge. Stock up on cherries, berries, sweet potatoes, spinach, oranges, walnuts, and dark chocolate for a delicious way to support muscle recovery and combat oxidative stress that could trigger inflammation and other health troubles down the road.
[319] 7 foods to boost antioxidant levels naturally - Times of India — Artichokes are also rich in antioxidants and are said to be rich in polyphenols, quercetin, and rutin, which protect cells from oxidative damage. They also contain vitamin C, luteolin, and
[320] Vitamin C, Vitamin E, Selenium, and β-Carotene and Other Carotenoids ... — This report focuses on vitamin C, vitamin E, selenium, and β-carotene and other carotenoids (α-carotene, β-cryptoxanthin, lutein, lycopene, and zeaxanthin). These compounds have frequently been called dietary antioxidants since in some cases they counteract oxidative damage to biomolecules (Halliwell, 1996), and the possibility exists that increased intakes of these compounds may protect