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Molecular Aspects of Medicine Aug 2011For the past 40 years or so, oxidative stress has been increasingly recognized as a contributing factor in aging and in various forms of pathophysiology generally... (Review)
Review
For the past 40 years or so, oxidative stress has been increasingly recognized as a contributing factor in aging and in various forms of pathophysiology generally associated with aging. Our view of oxidative stress has been largely "superoxide-centric", as we focused on the pathological sources of this oxygen-derived free radical and the types of molecular havoc it can wreak, as well as on the protection provided by the antioxidant enzymes, especially the superoxide dismutases, catalases, and glutathione peroxidases. In the last decade our view of oxidative stress has broadened considerably, and it is now often seen as an imbalance that has its origins in our genes, and the ways in which gene expression is regulated. At the center of this new focus is the transcription factor called nuclear factor (erythroid-derived 2)-like 2, or Nrf2. Nrf2 is referred to as the "master regulator" of the antioxidant response, modulating the expression of hundreds of genes, including not only the familiar antioxidant enzymes, but large numbers of genes that control seemingly disparate processes such as immune and inflammatory responses, tissue remodeling and fibrosis, carcinogenesis and metastasis, and even cognitive dysfunction and addictive behavior. Thus, the dysregulation of Nrf2-regulated genes provides a logical explanation for the connections, both direct and indirect, between observable oxidative stress and perhaps 200 human diseases involving these various physiological processes, each reflecting a network involving many gene products. The evolutionary self-association of these many genes under the common control of Nrf2 suggests that the immune and inflammatory systems may present the largest demand for increased antioxidant protection, apart from constitutive oxidative stress resulting from mitochondrial oxygen consumption for metabolic purposes. Gene expression microarray data on human primary vascular endothelial cells and on the SK-N-MC human neuroblastoma-derived cell line have been obtained in response to the dietary supplement Protandim, a potent composition of highly synergistic phytochemical Nrf2 activators. Pathway analysis of results shows significant modulation by Protandim of pathways involving not only antioxidant enzymes, but of those related to colon cancer, cardiovascular disease, and Alzheimer disease.
Topics: Animals; Antioxidants; Drugs, Chinese Herbal; Humans; Inflammation; NF-E2-Related Factor 2; Oxidative Stress; Signal Transduction
PubMed: 22020111
DOI: 10.1016/j.mam.2011.10.006 -
Redox Report : Communications in Free... Jul 2016Oxidative stress results from a prooxidant-antioxidant imbalance, leading to cellular damage. It is mediated by free radicals, such as reactive oxygen species or... (Review)
Review
Oxidative stress results from a prooxidant-antioxidant imbalance, leading to cellular damage. It is mediated by free radicals, such as reactive oxygen species or reactive nitrogen species, that are generated during physiological aerobic metabolism and pathological inflammatory processes. Skin serves as a protective organ that plays an important role in defending both external and internal toxic stimuli and maintaining homeostasis. It is becoming increasingly evident that oxidative stress is involved in numerous skin diseases and that antioxidative strategies can serve as effective and easy methods for improving these conditions. Herein, we review dysregulated antioxidant systems and antioxidative therapeutic strategies in dermatology.
Topics: Animals; Antioxidants; Dermatology; Humans; Oxidative Stress; Skin
PubMed: 26020527
DOI: 10.1179/1351000215Y.0000000015 -
Nutrients Sep 2019Cardiovascular diseases (CVD) are complex entities with heterogenous pathophysiologic mechanisms and increased oxidative stress has been viewed as one of the potential... (Review)
Review
Cardiovascular diseases (CVD) are complex entities with heterogenous pathophysiologic mechanisms and increased oxidative stress has been viewed as one of the potential common etiologies. A fine balance between the presence of reactive oxygen species (ROS) and antioxidants is essential for the proper normal functioning of the cell. A basal concentration of ROS is indispensable for the manifestation of cellular functions, whereas excessive levels of ROS cause damage to cellular macromolecules such as DNA, lipids and proteins, eventually leading to necrosis and apoptotic cell death. CVD is the main cause of death worldwide with several conditions being affected by oxidative stress. Increased ROS lead to decreased nitric oxide availability and vasoconstriction, promoting arterial hypertension. ROS also negatively influence myocardial calcium handling, causing arrhythmia, and augment cardiac remodeling by inducing hypertrophic signaling and apoptosis. Finally, ROS have also been shown to promote atherosclerotic plaque formation. This review aims at giving an introduction into oxidative stress in CVD, with special focus on endothelial dysfunction, and then examining in detail the role of oxidative stress in the most prevalent of these diseases. Finally, potential nutraceuticals and diets that might be beneficial in diminishing the burden of oxidative stress in CVD are presented.
Topics: Cardiovascular Diseases; Diet; Dietary Supplements; Humans; Inflammation; Oxidative Stress
PubMed: 31487802
DOI: 10.3390/nu11092090 -
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 -
Oxidative Medicine and Cellular... 2018There are different types of nutritionally mediated oxidative stress sources that trigger inflammation. Much information indicates that high intakes of macronutrients... (Review)
Review
There are different types of nutritionally mediated oxidative stress sources that trigger inflammation. Much information indicates that high intakes of macronutrients can promote oxidative stress and subsequently contribute to inflammation via nuclear factor-kappa B- (NF-B-) mediated cell signaling pathways. Dietary carbohydrates, animal-based proteins, and fats are important to highlight here because they may contribute to the long-term consequences of nutritionally mediated inflammation. Oxidative stress is a central player of metabolic ailments associated with high-carbohydrate and animal-based protein diets and excessive fat consumption. Obesity has become an epidemic and represents the major risk factor for several chronic diseases, including diabetes, cardiovascular disease (CVD), and cancer. However, the molecular mechanisms of nutritionally mediated oxidative stress are complex and poorly understood. Therefore, this review aimed to explore how dietary choices exacerbate or dampen the oxidative stress and inflammation. We also discussed the implications of oxidative stress in the adipocyte and glucose metabolism and obesity-associated noncommunicable diseases (NCDs). Taken together, a better understanding of the role of oxidative stress in obesity and the development of obesity-related NCDs would provide a useful approach. This is because oxidative stress can be mediated by both extrinsic and intrinsic factors, hence providing a plausible means for the prevention of metabolic disorders.
Topics: Food; Humans; Oxidative Stress
PubMed: 29643982
DOI: 10.1155/2018/9719584 -
Oxidative Medicine and Cellular... 2019Cardiovascular disease is a leading cause of death and reduced quality of life, proven by the latest data of the Global Burden of Disease Study, and is only gaining in... (Review)
Review
Cardiovascular disease is a leading cause of death and reduced quality of life, proven by the latest data of the Global Burden of Disease Study, and is only gaining in prevalence worldwide. Clinical trials have identified chronic inflammatory disorders as cardiovascular risks, and recent research has revealed a contribution by various inflammatory cells to vascular oxidative stress. Atherosclerosis and cardiovascular disease are closely associated with inflammation, probably due to the close interaction of inflammation with oxidative stress. Classical therapies for inflammatory disorders have demonstrated protective effects in various models of cardiovascular disease; especially established drugs with pleiotropic immunomodulatory properties have proven beneficial cardiovascular effects; normalization of oxidative stress seems to be a common feature of these therapies. The close link between inflammation and redox balance was also supported by reports on aggravated inflammatory phenotype in the absence of antioxidant defense proteins (e.g., superoxide dismutases, heme oxygenase-1, and glutathione peroxidases) or overexpression of reactive oxygen species producing enzymes (e.g., NADPH oxidases). The value of immunomodulation for the treatment of cardiovascular disease was recently supported by large-scale clinical trials demonstrating reduced cardiovascular mortality in patients with established atherosclerotic disease when treated by highly specific anti-inflammatory therapies (e.g., using monoclonal antibodies against cytokines). Modern antidiabetic cardiovascular drugs (e.g., SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 analogs) seem to share these immunomodulatory properties and display potent antioxidant effects, all of which may explain their successful lowering of cardiovascular risk.
Topics: Cardiovascular Diseases; Humans; Inflammation; Oxidative Stress
PubMed: 31341533
DOI: 10.1155/2019/7092151 -
Oxidative Medicine and Cellular... 2022With the acceleration of population aging, nervous system diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), anxiety,... (Review)
Review
With the acceleration of population aging, nervous system diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), anxiety, depression, stroke, and traumatic brain injury (TBI) have become a huge burden on families and society. The mechanism of neurological disorders is complex, which also lacks effective treatment, so relevant research is required to solve these problems urgently. Given that oxidative stress-induced lipid peroxidation eventually leads to ferroptosis, both oxidative stress and ferroptosis are important mechanisms causing neurological disorders, targeting mediators of oxidative stress and ferroptosis have become a hot research direction at present. Our review provides a current view of the mechanisms underlying ferroptosis and oxidative stress participate in neurological disorders, the potential application of molecular mediators targeting ferroptosis and oxidative stress in neurological disorders. The target of molecular mediators or agents of oxidative stress and ferroptosis associated with neurological disorders, such as reactive oxygen species (ROS), nuclear factor erythroid 2-related factor-antioxidant response element (Nrf2-ARE), n-acetylcysteine (NAC), Fe, NADPH, and its oxidases NOX, has been described in this article. Given that oxidative stress-induced ferroptosis plays a pivotal role in neurological disorders, further research on the mechanisms of ferroptosis caused by oxidative stress will help provide new targets for the treatment of neurological disorders.
Topics: Ferroptosis; Humans; Lipid Peroxidation; Nervous System Diseases; Oxidative Stress; Reactive Oxygen Species
PubMed: 35910843
DOI: 10.1155/2022/3999083 -
Biomedicine & Pharmacotherapy =... Dec 2018The role of oxidative stress in the occurrence and development of diabetes mellitus is both critical and pivotal. Several molecular event cascade in different metabolic... (Review)
Review
The role of oxidative stress in the occurrence and development of diabetes mellitus is both critical and pivotal. Several molecular event cascade in different metabolic pathways such as glycolytic, hexosamine, protein kinase C, polyol and advanced glycation end-product (AGE) pathways have been identified as pro-oxidative processes and are usually up-regulated in the diabetics. Inhibition of glyceraldehyde-3-P dehydrogenase by poly-ADP-ribose polymerase 1 and subsequent accumulation of the enzyme substrate (glyceraldehyde-3-P) appears to be central to diabetes-associated oxidative stress. Increased level of glyceraldehyde-3-P activates two major pro-oxidative pathways in diabetes: (i) It activates the AGE pathway, precisely the synthesis of methylglyoxal from non-enzymatic dephosphorylation of the triose phosphates (ii) It activates protein kinase C (PKC) pathway by promoting the synthesis of diacylglycerol. In addition, it causes the accumulation of glycolytic metabolites upstream, and this leads to excessive stimulation of other pro-oxidative pathways such as hexosamine and polyol pathways. This review tends to highlight the main oxidative processes associated with diabetes mellitus.
Topics: Animals; Diabetes Mellitus; Glycolysis; Humans; Metabolic Networks and Pathways; Oxidative Stress
PubMed: 30245465
DOI: 10.1016/j.biopha.2018.09.058 -
Molecular Medicine Reports Nov 2018Endoplasmic reticulum stress (ERS) can be induced by a variety of physiological and pathological factors including oxidative stress, which triggers the unfolded protein...
Endoplasmic reticulum stress (ERS) can be induced by a variety of physiological and pathological factors including oxidative stress, which triggers the unfolded protein response to deal with ERS. Autophagy has been hypothesized to be a means for tumor cells to increase cell survival under conditions of hypoxia, metabolic stress and even chemotherapy. Although they may function independently from each other, there are also interactions between responses to oxidative stress injury induced by pathologic and pharmacological factors. The aim of the present study was to investigate the effects of ERS and autophagy on H2O2‑induced oxidative stress injury in human HepG2 hepatoblastoma cells. It was demonstrated that exposure of HepG2 cells to H2O2 decreased cell viability and increased reactive oxygen species (ROS) levels in a dosage‑dependent manner. In addition, apoptosis and autophagy rates were elevated and reduced following cell exposure to H2O2 + the ERS inducer Tunicamycin (TM), and to H2O2 + the ERS inhibitor Salubrinal (SAL), compared with the cells treated with H2O2 alone, respectively. Further studies revealed that TM enhanced the expression of ERS‑related genes including glucose‑regulated protein‑78/binding immunoglobulin protein, inositol‑requiring kinase‑I and activating transcription factor 6 and C/EBP‑homologous protein 10, which were attenuated by SAL compared with cells exposed to H2O2 alone. The data from the present study also demonstrated that LC3II/LC3‑I and p62, members of autophagy‑related genes, were increased and decreased in cells treated with H2O2 + TM compared with cells treated with H2O2, respectively, indicating that autophagy was stimulated by ERS. Furthermore, a reduction in the levels of pro caspase‑3 and pro caspase‑9, and elevation level of caspase‑12 were observed in cells exposed to H2O2 + TM compared with cells treated with H2O2, respectively, suggesting apoptosis induced by H2O2 was enhanced by ERS or autophagy triggered by H2O2. The above results suggest that the ERS inducer may be a potential target for pharmacological intervention targeted to ERS or autophagy to enhance oxidative stress injury of tumor cells induced by antitumor drugs.
Topics: Apoptosis; Autophagy; Biomarkers; Cell Survival; Dose-Response Relationship, Drug; Endoplasmic Reticulum Stress; Gene Expression Regulation; Hep G2 Cells; Humans; Hydrogen Peroxide; Oxidative Stress; Reactive Oxygen Species
PubMed: 30221706
DOI: 10.3892/mmr.2018.9443 -
European Journal of Applied Physiology Apr 2019This review provides a current perspective on the mechanism of vitamin D on skeletal muscle function with the emphasis on oxidative stress, muscle anabolic state and... (Review)
Review
PURPOSE
This review provides a current perspective on the mechanism of vitamin D on skeletal muscle function with the emphasis on oxidative stress, muscle anabolic state and muscle energy metabolism. It focuses on several aspects related to cellular and molecular physiology such as VDR as the trigger point of vitamin D action, oxidative stress as a consequence of vitamin D deficiency.
METHOD
The interaction between vitamin D deficiency and mitochondrial function as well as skeletal muscle atrophy signalling pathways have been studied and clarified in the last years. To the best of our knowledge, we summarize key knowledge and knowledge gaps regarding the mechanism(s) of action of vitamin D in skeletal muscle.
RESULT
Vitamin D deficiency is associated with oxidative stress in skeletal muscle that influences the mitochondrial function and affects the development of skeletal muscle atrophy. Namely, vitamin D deficiency decreases oxygen consumption rate and induces disruption of mitochondrial function. These deleterious consequences on muscle may be associated through the vitamin D receptor (VDR) action. Moreover, vitamin D deficiency may contribute to the development of muscle atrophy. The possible signalling pathway triggering the expression of Atrogin-1 involves Src-ERK1/2-Akt- FOXO causing protein degradation.
CONCLUSION
Based on the current knowledge we propose that vitamin D deficiency results from the loss of VDR function and it could be partly responsible for the development of neurodegenerative diseases in human beings.
Topics: Animals; Energy Metabolism; Humans; Mitochondria; Muscle, Skeletal; Oxidative Stress; Vitamin D; Vitamin D Deficiency
PubMed: 30830277
DOI: 10.1007/s00421-019-04104-x