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Redox Biology 2015"Oxidative stress" as a concept in redox biology and medicine has been formulated in 1985; at the beginning of 2015, approx. 138,000 PubMed entries show for this term.... (Review)
Review
"Oxidative stress" as a concept in redox biology and medicine has been formulated in 1985; at the beginning of 2015, approx. 138,000 PubMed entries show for this term. This concept has its merits and its pitfalls. Among the merits is the notion, elicited by the combined two terms of (i) aerobic metabolism as a steady-state redox balance and (ii) the associated potential strains in the balance as denoted by the term, stress, evoking biological stress responses. Current research on molecular redox switches governing oxidative stress responses is in full bloom. The fundamental importance of linking redox shifts to phosphorylation/dephosphorylation signaling is being more fully appreciated, thanks to major advances in methodology. Among the pitfalls is the fact that the underlying molecular details are to be worked out in each particular case, which is bvious for a global concept, but which is sometimes overlooked. This can lead to indiscriminate use of the term, oxidative stress, without clear relation to redox chemistry. The major role in antioxidant defense is fulfilled by antioxidant enzymes, not by small-molecule antioxidant compounds. The field of oxidative stress research embraces chemistry, biochemistry, cell biology, physiology and pathophysiology, all the way to medicine and health and disease research.
Topics: Antioxidants; Humans; Oxidation-Reduction; Oxidative Stress; Signal Transduction
PubMed: 25588755
DOI: 10.1016/j.redox.2015.01.002 -
Nature Reviews. Drug Discovery Sep 2021Oxidative stress is a component of many diseases, including atherosclerosis, chronic obstructive pulmonary disease, Alzheimer disease and cancer. Although numerous small... (Review)
Review
Oxidative stress is a component of many diseases, including atherosclerosis, chronic obstructive pulmonary disease, Alzheimer disease and cancer. Although numerous small molecules evaluated as antioxidants have exhibited therapeutic potential in preclinical studies, clinical trial results have been disappointing. A greater understanding of the mechanisms through which antioxidants act and where and when they are effective may provide a rational approach that leads to greater pharmacological success. 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.
Topics: Animals; Antioxidants; Drug Development; Drug Evaluation, Preclinical; Humans; Molecular Targeted Therapy; Oxidation-Reduction; Oxidative Stress; Signal Transduction
PubMed: 34194012
DOI: 10.1038/s41573-021-00233-1 -
International Journal of Molecular... May 2022Oxidative 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... (Review)
Review
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 disease, and amyotrophic lateral sclerosis. Oxidative stress was also noted to modify the inflammatory response. Even though oxidative stress and neuroinflammation are two totally different pathological events, they are linked and affect one another. Nonetheless, there are still several mechanisms that need to be understood regarding the onset and the progress of neurodegenerative diseases in order to develop efficient therapies. As antioxidants are a means to alter oxidative stress and slow down the symptoms of these neurodegenerative diseases, the most common antioxidants, enzymatic as well as non-enzymatic, have been mentioned in this paper as therapeutic options for the discussed disorders.
Topics: Antioxidants; Humans; Neurodegenerative Diseases; Neuroinflammatory Diseases; Oxidative Stress; Reactive Oxygen Species
PubMed: 35682615
DOI: 10.3390/ijms23115938 -
Neuroscience Bulletin Apr 2014Oxidative stress plays a significant role in the pathogenesis of Alzheimer's disease (AD), a devastating disease of the elderly. The brain is more vulnerable than other... (Review)
Review
Oxidative stress plays a significant role in the pathogenesis of Alzheimer's disease (AD), a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons (lipids, proteins, and nucleic acids) can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid (Aβ) peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.
Topics: Alzheimer Disease; Animals; Humans; Oxidative Stress
PubMed: 24664866
DOI: 10.1007/s12264-013-1423-y -
Cell Death and Differentiation Mar 2015Autophagy is a catabolic process aimed at recycling cellular components and damaged organelles in response to diverse conditions of stress, such as nutrient deprivation,... (Review)
Review
Autophagy is a catabolic process aimed at recycling cellular components and damaged organelles in response to diverse conditions of stress, such as nutrient deprivation, viral infection and genotoxic stress. A growing amount of evidence in recent years argues for oxidative stress acting as the converging point of these stimuli, with reactive oxygen species (ROS) and reactive nitrogen species (RNS) being among the main intracellular signal transducers sustaining autophagy. This review aims at providing novel insight into the regulatory pathways of autophagy in response to glucose and amino acid deprivation, as well as their tight interconnection with metabolic networks and redox homeostasis. The role of oxidative and nitrosative stress in autophagy is also discussed in the light of its being harmful for both cellular biomolecules and signal mediator through reversible posttranslational modifications of thiol-containing proteins. The redox-independent relationship between autophagy and antioxidant response, occurring through the p62/Keap1/Nrf2 pathway, is also addressed in order to provide a wide perspective upon the interconnection between autophagy and oxidative stress. Herein, we also attempt to afford an overview of the complex crosstalk between autophagy and DNA damage response (DDR), focusing on the main pathways activated upon ROS and RNS overproduction. Along these lines, the direct and indirect role of autophagy in DDR is dissected in depth.
Topics: Animals; Autophagy; Homeostasis; Humans; Oxidative Stress; Signal Transduction
PubMed: 25257172
DOI: 10.1038/cdd.2014.150 -
American Journal of Physiology. Cell... Oct 2008Free radical-induced macromolecular damage has been studied extensively as a mechanism of oxidative stress, but large-scale intervention trials with free radical... (Review)
Review
Free radical-induced macromolecular damage has been studied extensively as a mechanism of oxidative stress, but large-scale intervention trials with free radical scavenging antioxidant supplements show little benefit in humans. The present review summarizes data supporting a complementary hypothesis for oxidative stress in disease that can occur without free radicals. This hypothesis, which is termed the "redox hypothesis," is that oxidative stress occurs as a consequence of disruption of thiol redox circuits, which normally function in cell signaling and physiological regulation. The redox states of thiol systems are sensitive to two-electron oxidants and controlled by the thioredoxins (Trx), glutathione (GSH), and cysteine (Cys). Trx and GSH systems are maintained under stable, but nonequilibrium conditions, due to a continuous oxidation of cell thiols at a rate of about 0.5% of the total thiol pool per minute. Redox-sensitive thiols are critical for signal transduction (e.g., H-Ras, PTP-1B), transcription factor binding to DNA (e.g., Nrf-2, nuclear factor-kappaB), receptor activation (e.g., alphaIIbbeta3 integrin in platelet activation), and other processes. Nonradical oxidants, including peroxides, aldehydes, quinones, and epoxides, are generated enzymatically from both endogenous and exogenous precursors and do not require free radicals as intermediates to oxidize or modify these thiols. Because of the nonequilibrium conditions in the thiol pathways, aberrant generation of nonradical oxidants at rates comparable to normal oxidation may be sufficient to disrupt function. Considerable opportunity exists to elucidate specific thiol control pathways and develop interventional strategies to restore normal redox control and protect against oxidative stress in aging and age-related disease.
Topics: Free Radicals; Oxidants; Oxidative Stress
PubMed: 18684987
DOI: 10.1152/ajpcell.00283.2008 -
Annual Review of Pharmacology and... 2013Organismal life encounters reactive oxidants from internal metabolism and environmental toxicant exposure. Reactive oxygen and nitrogen species cause oxidative stress... (Review)
Review
Organismal life encounters reactive oxidants from internal metabolism and environmental toxicant exposure. Reactive oxygen and nitrogen species cause oxidative stress and are traditionally viewed as being harmful. On the other hand, controlled production of oxidants in normal cells serves useful purposes to regulate signaling pathways. Reactive oxidants are counterbalanced by complex antioxidant defense systems regulated by a web of pathways to ensure that the response to oxidants is adequate for the body's needs. A recurrent theme in oxidant signaling and antioxidant defense is reactive cysteine thiol-based redox signaling. The nuclear factor erythroid 2-related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants. Nrf2 controls the basal and induced expression of an array of antioxidant response element-dependent genes to regulate the physiological and pathophysiological outcomes of oxidant exposure. This review discusses the impact of Nrf2 on oxidative stress and toxicity and how Nrf2 senses oxidants and regulates antioxidant defense.
Topics: Animals; Antioxidants; Humans; NF-E2-Related Factor 2; Oxidants; Oxidative Stress
PubMed: 23294312
DOI: 10.1146/annurev-pharmtox-011112-140320 -
Pediatric Nephrology (Berlin, Germany) Jun 2019Oxidative stress (OS), defined as disturbances in the pro-/antioxidant balance, is harmful to cells due to the excessive generation of highly reactive oxygen (ROS) and... (Review)
Review
Oxidative stress (OS), defined as disturbances in the pro-/antioxidant balance, is harmful to cells due to the excessive generation of highly reactive oxygen (ROS) and nitrogen (RNS) species. When the balance is not disturbed, OS has a role in physiological adaptations and signal transduction. However, an excessive amount of ROS and RNS results in the oxidation of biological molecules such as lipids, proteins, and DNA. Oxidative stress has been reported in kidney disease, due to both antioxidant depletions as well as increased ROS production. The kidney is a highly metabolic organ, rich in oxidation reactions in mitochondria, which makes it vulnerable to damage caused by OS, and several studies have shown that OS can accelerate kidney disease progression. Also, in patients at advanced stages of chronic kidney disease (CKD), increased OS is associated with complications such as hypertension, atherosclerosis, inflammation, and anemia. In this review, we aim to describe OS and its influence on CKD progression and its complications. We also discuss the potential role of various antioxidants and pharmacological agents, which may represent potential therapeutic targets to reduce OS in both pediatric and adult CKD patients.
Topics: Animals; Humans; Oxidative Stress; Renal Insufficiency, Chronic
PubMed: 30105414
DOI: 10.1007/s00467-018-4005-4 -
Oncotarget Jul 2016Aging and cancer are the most important issues to research. The population in the world is growing older, and the incidence of cancer increases with age. There is no... (Review)
Review
Aging and cancer are the most important issues to research. The population in the world is growing older, and the incidence of cancer increases with age. There is no doubt about the linkage between aging and cancer. However, the molecular mechanisms underlying this association are still unknown. Several lines of evidence suggest that the oxidative stress as a cause and/or consequence of the mitochondrial dysfunction is one of the main drivers of these processes. Increasing ROS levels and products of the oxidative stress, which occur in aging and age-related disorders, were also found in cancer. This review focuses on the similarities between ageing-associated and cancer-associated oxidative stress and mitochondrial dysfunction as their common phenotype.
Topics: Aging; Animals; Humans; Mitochondria; Neoplasms; Oxidative Stress
PubMed: 27270647
DOI: 10.18632/oncotarget.9821 -
European Journal of Heart Failure Apr 2019Advances in cardiovascular research have identified oxidative stress as an important pathophysiological pathway in the development and progression of heart failure.... (Review)
Review
Advances in cardiovascular research have identified oxidative stress as an important pathophysiological pathway in the development and progression of heart failure. Oxidative stress is defined as the imbalance between the production of reactive oxygen species (ROS) and the endogenous antioxidant defence system. Under physiological conditions, small quantities of ROS are produced intracellularly, which function in cell signalling, and can be readily reduced by the antioxidant defence system. However, under pathophysiological conditions, the production of ROS exceeds the buffering capacity of the antioxidant defence system, resulting in cell damage and death. Over the last decades several studies have tried to target oxidative stress with the aim to improve outcome in patients with heart failure, with very limited success. The reasons as to why these studies failed to demonstrate any beneficial effects remain unclear. However, one plausible explanation might be that currently employed strategies, which target oxidative stress by exogenous inhibition of ROS production or supplementation of exogenous antioxidants, are not effective enough, while bolstering the endogenous antioxidant capacity might be a far more potent avenue for therapeutic intervention. In this review, we provide an overview of oxidative stress in the pathophysiology of heart failure and the strategies utilized to date to target this pathway. We provide novel insights into modulation of endogenous antioxidants, which may lead to novel therapeutic strategies to improve outcome in patients with heart failure.
Topics: Animals; Antioxidants; Disease Models, Animal; Heart Failure; Humans; Oxidative Stress; Reactive Oxygen Species
PubMed: 30338885
DOI: 10.1002/ejhf.1320