Oxidative Stress, Classification and Quantitation

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 40145

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Department of Physiology and Pharmacology, Sackler Medical School, Tel Aviv University, Tel Aviv 6997801, Israel
Interests: physical chemistry of lipids, liposomes, and micelles; detergent solubilization of lipid free radicals; oxidative stress; antioxidants; pro-oxidants
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Dear Colleagues,

Oxidative stress (OS) is an ill-defined term, being dependent on the method used to evaluate it. Quantitation based on the steady state concentration of any given biomarker quite often correlates with the OS based on other biomarkers, but even when the correlation is highly significant, it is low. This may be attributed to the nature of the different biomarkers. Specifically, different biomarkers may reflect different manifestations of the OS or different types of OS. We think that different manifestations of the same process are more likely to correlate with each other than different “types”. Hence, we hypothesize that several types of OS exist. This conclusion accords with the proposal of Halliwell and Gutteridge. These authors proposed that “chemistries of different ROS entities are distinct”. This means that OS can be divided into subgroups with different ROS (“types of OS”).

Given the very large number of oxidants and the huge differences between the reactivity of different targets, the concentration of a single biomarker cannot be expected to give an answer to the overall capacity of an individual to resist oxidative damage and cannot be of diagnostic value. Several researchers have tried to quantitate OS by integrating a battery of oxidation-relevant biomarkers. The way to integrate the information on the steady state concentrations of several biomarkers is very complex, particularly because antioxidants contribute to the overall oxidative status, and we know that low molecular weight antioxidants may either reduce or promote the OS, depending on the conditions.

Another important aspect of the specific type of OS is that it may be relevant to the prevailing hypothesis that high-risk groups benefit most from antioxidant interventions. This hypothesis is the basis for the “identify and treat” approach, which is that high OS is a risk factor of oxidative damages, so that monitoring of the OS, followed by antioxidant treatment of people under high OS, “may improve patient management decisions and patient outcomes”. The lack of a universal criterion of OS is of course a major problem. In addition, the “identify and treat” approach ignores the possible pro-oxidative effect of low molecular weight antioxidants. Altogether, as long as we do not know the pathophysiological meaning of the different types of OS, the search for improved methods of quantifying OS is of limited applied value.

Prof. Dr. Dov Lichtenberg
Guest Editor

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Keywords

  • oxidative stress
  • antioxidants
  • evaluation
  • types
  • subgroups
  • classification
  • quantitation

Published Papers (6 papers)

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Research

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21 pages, 5092 KiB  
Article
Development of an Analytical Assay for Electrochemical Detection and Quantification of Protein-Bound 3-Nitrotyrosine in Biological Samples and Comparison with Classical, Antibody-Based Methods
by Ksenija Vujacic-Mirski, Kai Bruns, Sanela Kalinovic, Matthias Oelze, Swenja Kröller-Schön, Sebastian Steven, Milos Mojovic, Bato Korac, Thomas Münzel and Andreas Daiber
Antioxidants 2020, 9(5), 388; https://doi.org/10.3390/antiox9050388 - 6 May 2020
Cited by 7 | Viewed by 3568
Abstract
Reactive oxygen and nitrogen species (RONS) cause oxidative damage, which is associated with endothelial dysfunction and cardiovascular disease, but may also contribute to redox signaling. Therefore, their precise detection is important for the evaluation of disease mechanisms. Here, we compared three different methods [...] Read more.
Reactive oxygen and nitrogen species (RONS) cause oxidative damage, which is associated with endothelial dysfunction and cardiovascular disease, but may also contribute to redox signaling. Therefore, their precise detection is important for the evaluation of disease mechanisms. Here, we compared three different methods for the detection of 3-nitrotyrosine (3-NT), a marker of nitro-oxidative stress, in biological samples. Nitrated proteins were generated by incubation with peroxynitrite or 3-morpholino sydnonimine (Sin-1) and subjected to total hydrolysis using pronase, a mixture of different proteases. The 3-NT was then separated by high performance liquid chromatography (HPLC) and quantified by electrochemical detection (ECD, CoulArray) and compared to classical methods, namely enzyme-linked immunosorbent assay (ELISA) and dot blot analysis using specific 3-NT antibodies. Calibration curves for authentic 3-NT (detection limit 10 nM) and a concentration-response pattern for 3-NT obtained from digested nitrated bovine serum albumin (BSA) were highly linear over a wide 3-NT concentration range. Also, ex vivo nitration of protein from heart, isolated mitochondria, and serum/plasma could be quantified using the HPLC/ECD method and was confirmed by LC-MS/MS. Of note, nitro-oxidative damage of mitochondria results in increased superoxide (O2•–) formation rates (measured by dihydroethidium-based HPLC assay), pointing to a self-amplification mechanism of oxidative stress. Based on our ex vivo data, the CoulArray quantification method for 3-NT seems to have some advantages regarding sensitivity and selectivity. Establishing a reliable automated HPLC assay for the routine quantification of 3-NT in biological samples of cell culture, of animal and human origin seems to be more sophisticated than expected. Full article
(This article belongs to the Special Issue Oxidative Stress, Classification and Quantitation)
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Review

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24 pages, 1692 KiB  
Review
Approaches for Reactive Oxygen Species and Oxidative Stress Quantification in Epilepsy
by Rhoda Olowe, Sereen Sandouka, Aseel Saadi and Tawfeeq Shekh-Ahmad
Antioxidants 2020, 9(10), 990; https://doi.org/10.3390/antiox9100990 - 14 Oct 2020
Cited by 50 | Viewed by 5127
Abstract
Oxidative stress (OS) and excessive reactive oxygen species (ROS) production have been implicated in many neurological pathologies, including acute seizures and epilepsy. Seizure-induced damage has been demonstrated both in vitro and in several in vivo seizure and epilepsy models by direct determination of [...] Read more.
Oxidative stress (OS) and excessive reactive oxygen species (ROS) production have been implicated in many neurological pathologies, including acute seizures and epilepsy. Seizure-induced damage has been demonstrated both in vitro and in several in vivo seizure and epilepsy models by direct determination of ROS, and by measuring indirect markers of OS. In this manuscript, we review the current reliable methods for quantifying ROS-related and OS-related markers in pre-clinical and clinical epilepsy studies. We first provide pieces of evidence for the involvement of different sources of ROS in epilepsy. We then discuss general methods and assays used for the ROS measurements, mainly superoxide anion, hydrogen peroxide, peroxynitrite, and hydroxyl radical in in vitro and in vivo studies. In addition, we discuss the role of these ROS and markers of oxidative injury in acute seizures and epilepsy pre-clinical studies. The indirect detection of secondary products of ROS such as measurements of DNA damage, lipid peroxidation, and protein oxidation will also be discussed. This review also discusses reliable methods for the assessment of ROS, OS markers, and their by-products in epilepsy clinical studies. Full article
(This article belongs to the Special Issue Oxidative Stress, Classification and Quantitation)
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20 pages, 1260 KiB  
Review
Polyphenols by Generating H2O2, Affect Cell Redox Signaling, Inhibit PTPs and Activate Nrf2 Axis for Adaptation and Cell Surviving: In Vitro, In Vivo and Human Health
by Joseph Kanner
Antioxidants 2020, 9(9), 797; https://doi.org/10.3390/antiox9090797 - 27 Aug 2020
Cited by 55 | Viewed by 6117
Abstract
Human health benefits from different polyphenols molecules consumption in the diet, derived mainly by their common activities in the gastrointestinal tract and at the level of blood micro-capillary. In the stomach, intestine and colon, polyphenols act as reducing agents preventing lipid peroxidation, generation [...] Read more.
Human health benefits from different polyphenols molecules consumption in the diet, derived mainly by their common activities in the gastrointestinal tract and at the level of blood micro-capillary. In the stomach, intestine and colon, polyphenols act as reducing agents preventing lipid peroxidation, generation and absorption of AGEs/ALEs (advanced glycation end products/advanced lipid oxidation end products) and postprandial oxidative stress. The low absorption of polyphenols in blood does not support their activity as antioxidants and their mechanism of activity is not fully understood. The results are from in vitro, animal and human studies, detected by relevant oxidative stress markers. The review carries evidences that polyphenols, by generating H2O2 at nM concentration, exogenous to cells and organs, act as activators of signaling factors increasing cell Eustress. When polyphenols attain high concentration in the blood system, they generate H2O2 at µM concentration, acting as cytotoxic agents and Distress. Pre-treatment of cells or organisms with polyphenols, by generating H2O2 at low levels, inhibits cellular PTPs (protein tyrosine phosphatases), inducing cell signaling through transcription of the Nrf2 (nuclear factor erythroid 2-related factor 2) axis of adaptation and protection to oxidation stress. Polyphenols ingestion at the right amount and time during the meal acts synergistically at the level of the gastrointestinal tract (GIT) and blood system, for keeping the redox homeostasis in our organism and better balancing human health. Full article
(This article belongs to the Special Issue Oxidative Stress, Classification and Quantitation)
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18 pages, 733 KiB  
Review
Cellular Aging Characteristics and Their Association with Age-Related Disorders
by Magdalena Rudzińska, Alessandro Parodi, Anastasia V. Balakireva, Olga E. Chepikova, Franco M. Venanzi and Andrey A. Zamyatnin, Jr.
Antioxidants 2020, 9(2), 94; https://doi.org/10.3390/antiox9020094 - 22 Jan 2020
Cited by 23 | Viewed by 4130
Abstract
Different molecular signaling pathways, biological processes, and intercellular communication mechanisms control longevity and are affected during cellular senescence. Recent data have suggested that organelle communication, as well as genomic and metabolic dysfunctions, contribute to this phenomenon. Oxidative stress plays a critical role by [...] Read more.
Different molecular signaling pathways, biological processes, and intercellular communication mechanisms control longevity and are affected during cellular senescence. Recent data have suggested that organelle communication, as well as genomic and metabolic dysfunctions, contribute to this phenomenon. Oxidative stress plays a critical role by inducing structural modifications to biological molecules while affecting their function and catabolism and eventually contributing to the onset of age-related dysfunctions. In this scenario, proteins are not adequately degraded and accumulate in the cell cytoplasm as toxic aggregates, increasing cell senescence progression. In particular, carbonylation, defined as a chemical reaction that covalently and irreversibly modifies proteins with carbonyl groups, is considered to be a significant indicator of protein oxidative stress and aging. Here, we emphasize the role and dysregulation of the molecular pathways controlling cell metabolism and proteostasis, the complexity of the mechanisms that occur during aging, and their association with various age-related disorders. The last segment of the review details current knowledge on protein carbonylation as a biomarker of cellular senescence in the development of diagnostics and therapeutics for age-related dysfunctions. Full article
(This article belongs to the Special Issue Oxidative Stress, Classification and Quantitation)
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Other

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12 pages, 782 KiB  
Opinion
The Cutaneous Physiological Redox: Essential to Maintain but Difficult to Define
by Sapir Ron-Doitch and Ron Kohen
Antioxidants 2020, 9(10), 942; https://doi.org/10.3390/antiox9100942 - 1 Oct 2020
Cited by 9 | Viewed by 2507
Abstract
Skin is a unique tissue, possessing extremely efficient protective and regulative mechanisms, similar only to the gut and lungs. These tissues serve as an interface with the environment and are exposed to stressors from both endogenous and exogenous sources. Interestingly, all these stressors [...] Read more.
Skin is a unique tissue, possessing extremely efficient protective and regulative mechanisms, similar only to the gut and lungs. These tissues serve as an interface with the environment and are exposed to stressors from both endogenous and exogenous sources. Interestingly, all these stressors lead downstream to a cellular production of reactive oxygen species (ROS) and other electrophiles, which, in turn could have deleterious outcomes for the living organism. Hence, such tissues should always maintain a “high-alert” condition in order to cope with these various insults. Nevertheless, a moderate production of ROS induced by stressors could actually be beneficial, although it is impossible to predict if and which exposure would lead to which outcome. Consequently, a parameter which would indicate the skin’s readiness to cope with continuously fluctuating conditions is required. It has been proposed that the redox status may serve as a suitable indicator. In this opinion manuscript, we argue that the redox status is a vague parameter that is difficult to characterized and quantify due to its extremely dynamic nature. The common convention that the redox status is composed solely of the balance between oxidants and reductants (ROS and antioxidants) is also thought-provoking. Since this parameter in vivo behaves in a dynamic and complex manner, it better fits the description of a process, rather than an individual parameter. We suggest that the homeostatic modulation of the physiological redox (PR) should be in focus, rather than the redox status parameter itself. It is further suggested that low molecular weight antioxidants (LMWA) are, in fact, rather insignificant concerning the PR maintenance, and that the major contributors to this delicate modulation are regulative, protein-based systems such as the protective phase II antioxidant enzymes. Moreover, we show that skin microbiome and cutaneous advanced lipid peroxidation end-products (ALEs) take part in sustaining the cutaneous PR homoeostasis via activation of the Nrf2–Keap1 protective pathway. Full article
(This article belongs to the Special Issue Oxidative Stress, Classification and Quantitation)
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6 pages, 1181 KiB  
Commentary
Oxidative Stress: Concept and Some Practical Aspects
by Helmut Sies
Antioxidants 2020, 9(9), 852; https://doi.org/10.3390/antiox9090852 - 10 Sep 2020
Cited by 207 | Viewed by 17581
Abstract
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”. This Commentary presents basic features of this global concept which has attracted interest in biology [...] Read more.
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”. This Commentary presents basic features of this global concept which has attracted interest in biology and medicine. The term “antioxidants” in cellular defense against oxidants predominantly includes antioxidant enzymes with their substrates and coenzymes. Exogenous low-molecular-mass compounds also have a role, but this is more limited. 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. Full article
(This article belongs to the Special Issue Oxidative Stress, Classification and Quantitation)
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