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Concept: Free-radical theory


A novel antioxidant regenerating system consisting of cellobiose dehydrogenase (CDH), cellobiose and phenolic antioxidants with potential application for continuous quenching of free radical species in chronic wounds was developed. This antioxidant regenerating system, continuously quenched in situ produced .NO, O(2)(•-) and OH(•) radicals and the produced oxidized phenolic antioxidants were regenerated back to their original parent compounds by CDH using cellobiose as electron donor. This system therefore prevented the accumulation of oxidized phenolic antioxidants. Interestingly, this study also challenges the relevance of using total antioxidant capacities values of plant crude extracts obtained using biologically none relevant radical species like (2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox Equivalent Antioxidant Capacity (TEAC) etc. when applied as medicinal remedies. This is because methoxylated phenolic antioxidants like sinapic acid, ferulic acid; 2,6-dimethoxyphenol readily donate their electrons to these radicals (DPPH, TEAC etc.) thereby greatly influencing the total antioxidant values although this study showed that they are not at all effective in quenching O(2)(•-) radicals and again are not the most effective quenchers of .NO and OH(•) radicals as demonstrated during this study.

Concepts: Atherosclerosis, Oxidative stress, Radical, Vitamin C, Nitric oxide, Free-radical theory, Matrix-assisted laser desorption/ionization, Oxygen radical absorbance capacity


Longevity and aging are differently regulated. Longevity has an important part of genetic determinants, aging is essentially post-genetic. Among the genes involved in longevity determination, sirtuins, activated also by calorie restriction and some others as the TOR pathway, attracted special interest after the insulin-IGF pathway first shown to regulate longevity in model organisms. For most of these genes, postponement of life-threatening diseases is the basis of their action which never exceeds about 35% of all determinants, in humans. Among the post-genetic mechanisms responsible for age-related decline of function, free radicals attracted early interest as well as the Maillard reaction, generating also free radicals. Most attempts to remediate to free radical damage failed however, although different scavenger mechanisms and protective substances are present in the organism. Synthetic protectors were also tested without success. The only example of a successful treatment of a free radical mediated pathology is the case of xanthine oxidase, involved in cardiovascular pathology, essentially during the ischemia-reperfusion process. Its inhibition by allopurinol is currently used to fight this deadly syndrome.

Concepts: DNA, Gene, Senescence, Biology, Organism, Chemical reaction, Free-radical theory, Free radicals


In this study, five different kinds of polysaccharides (AAP1, AAP2, AAP3, AAP4, and AAP5) were extracted from different varieties of Auricularia auricula through an alkali extraction process. Furthermore, the crude polysaccharides were deproteinized by the Sevag method. Auricularia auricula produced in the Shanxi province had the highest content of polysaccharide, 53.02%. The monosaccharide composition was determined by the GC method. Their antioxidant capacities in vitro were assessed by radical-scavenging capacity (DPPH, superoxide, and hydroxyl radicals), metal chelating ability and reducing-power methods. In addition, the evaluation of their antioxidant effects in vivo was performed using the C. elegans model. The yield of crude polysaccharides, monosaccharide composition and antioxidant activity of Auricularia auricula polysaccharides (AAPs) were different among samples from various sources. Among them, the strongest antioxidant activity was shown for AAP1, consisting of arabinose, xylose, 2-deoxy-d-glucose, mannose, glucose, and N-acetyl-d-glucosamine with the molar ratio of 1 : 0.44 : 0.33 : 1.67 : 1 : 0.17. It could scavenge free radicals, up-regulate stress-resistance-related enzymes including superoxide dismutase (SOD) by 70.04 ± 8.75% and CAT by 117.32 ± 8.06% and reduce the level of reactive oxygen species (ROS) in C. elegans under oxidative stress. The present results suggested that variety was an important factor that affects the antioxidant activity of A. auricula polysaccharides.

Concepts: Antioxidant, Oxidative stress, Oxidative phosphorylation, Reactive oxygen species, Superoxide dismutase, Carbohydrate, Free-radical theory, Monosaccharide


While oxidative damage owing to reactive oxygen species (ROS) often increases with advancing age and is associated with many age-related diseases, its causative role in ageing is controversial. In particular, studies that have attempted to modulate ROS-induced damage, either upwards or downwards, using antioxidant or genetic approaches, generally do not show a predictable effect on lifespan. Here, we investigated whether dietary supplementation with either vitamin E (α-tocopherol) or vitamin C (ascorbic acid) affected oxidative damage and lifespan in short-tailed field voles, Microtus agrestis. We predicted that antioxidant supplementation would reduce ROS-induced oxidative damage and increase lifespan relative to unsupplemented controls. Antioxidant supplementation for nine months reduced hepatic lipid peroxidation, but DNA oxidative damage to hepatocytes and lymphocytes was unaffected. Surprisingly, antioxidant supplementation significantly shortened lifespan in voles maintained under both cold (7 ± 2°C) and warm (22 ± 2°C) conditions. These data further question the predictions of free-radical theory of ageing and critically, given our previous research in mice, indicate that similar levels of antioxidants can induce widely different interspecific effects on lifespan.

Concepts: Antioxidant, Oxidative stress, Oxidative phosphorylation, Reactive oxygen species, Vitamin C, Free-radical theory, Lipid peroxidation, Ascorbic acid


Overproduction of oxidants (reactive oxygen species and reactive nitrogen species) in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought to be an effective measure to depress the level of oxidative stress of organisms. It has been reported that intake of vegetables and fruits is inversely associated with the risk of many chronic diseases, and antioxidant phytochemicals in vegetables and fruits are considered to be responsible for these health benefits. Antioxidant phytochemicals can be found in many foods and medicinal plants, and play an important role in the prevention and treatment of chronic diseases caused by oxidative stress. They often possess strong antioxidant and free radical scavenging abilities, as well as anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative diseases. This review summarizes recent progress on the health benefits of antioxidant phytochemicals, and discusses their potential mechanisms in the prevention and treatment of chronic diseases.

Concepts: Oxygen, Medicine, Nutrition, Antioxidant, Oxidative stress, Oxidative phosphorylation, Reactive oxygen species, Free-radical theory


Life-history theory assumes that reproduction entails a cost, and research on cooperatively breeding societies suggests that the cooperative sharing of workloads can reduce this cost. However, the physiological mechanisms that underpin both the costs of reproduction and the benefits of cooperation remain poorly understood. It has been hypothesized that reproductive costs may arise in part from oxidative stress, as reproductive investment may elevate exposure to reactive oxygen species, compromising survival and future reproduction and accelerating senescence. However, experimental evidence of oxidative costs of reproduction in the wild remains scarce. Here, we use a clutch-removal experiment to investigate the oxidative costs of reproduction in a wild cooperatively breeding bird, the white-browed sparrow weaver, Plocepasser mahali. Our results reveal costs of reproduction that are dependent on group size: relative to individuals in groups whose eggs were experimentally removed, individuals in groups that raised offspring experienced an associated cost (elevated oxidative damage and reduced body mass), but only if they were in small groups containing fewer or no helpers. Furthermore, during nestling provisioning, individuals that provisioned at higher rates showed greater within-individual declines in body mass and antioxidant protection. Our results provide rare experimental evidence that reproduction can negatively impact both oxidative status and body mass in the wild, and suggest that these costs can be mitigated in cooperative societies by the presence of additional helpers. These findings have implications for our understanding of the energetic and oxidative costs of reproduction, and the benefits of cooperation in animal societies.

Concepts: Antioxidant, Oxidative stress, Oxidative phosphorylation, Reactive oxygen species, Superoxide dismutase, Hydrogen peroxide, Glutathione, Free-radical theory


It is well known that oxidative stress induces larynx cancer, although antioxidants induce modulator role on etiology of the cancer. It is well known that electromagnetic radiation (EMR) induces oxidative stress in different cell systems. The aim of this study was to investigate the possible protective role of melatonin on oxidative stress induced by Wi-Fi (2.45 GHz) EMR in laryngotracheal mucosa of rat. For this purpose, 32 male rats were equally categorized into four groups, namely controls, sham controls, EMR-exposed rats, EMR-exposed rats treated with melatonin at a dose of 10 mg/kg/day. Except for the controls and sham controls, the animals were exposed to 2.45 GHz radiation during 60 min/day for 28 days. The lipid peroxidation levels were significantly (p < 0.05) higher in the radiation-exposed groups than in the control and sham control groups. The lipid peroxidation level in the irradiated animals treated with melatonin was significantly (p < 0.01) lower than in those that were only exposed to Wi-Fi radiation. The activity of glutathione peroxidase was lower in the irradiated-only group relative to control and sham control groups but its activity was significantly (p < 0.05) increased in the groups treated with melatonin. The reduced glutathione levels in the mucosa of rat did not change in the four groups. There is an apparent protective effect of melatonin on the Wi-Fi-induced oxidative stress in the laryngotracheal mucosa of rats by inhibition of free radical formation and support of the glutathione peroxidase antioxidant system.

Concepts: Antioxidant, Oxidative stress, Reactive oxygen species, Radical, Glutathione, Glutathione peroxidase, Free-radical theory, Antioxidants


Testing the predictions of the Mitochondrial Free Radical Theory of Ageing (MFRTA) has provided a deep understanding of the role of reactive oxygen species (ROS) and mitochondria in the ageing process. However those data, which support MFRTA are in the majority correlative (e.g. increasing oxidative damage with age). In contrast the majority of direct experimental data contradict MFRTA (e.g. changes in ROS levels do not alter longevity as expected). Unfortunately, in the past, ROS measurements have mainly been performed using isolated mitochondria, a method which is prone to experimental artefacts and does not reflect the complexity of the in vivo process. New technology to study different ROS (e.g. superoxide or hydrogen peroxide) in vivo is now available; these new methods combined with state-of-the-art genetic engineering technology will allow a deeper interrogation of, where, when and how free radicals affect ageing and pathological processes. In fact data that combine these new approaches, indicate that boosting mitochondrial ROS in lower animals is a way to extend both healthy and maximum lifespan. In this review, I discuss the latest literature focused on the role of mitochondrial ROS in ageing, and how these new discoveries are helping to better understand the role of mitochondria in health and disease. This article is part of a Special Issue entitled ‘EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016’, edited by Prof. Paolo Bernardi.

Concepts: Oxygen, Senescence, Mitochondrion, Oxidative stress, Oxidative phosphorylation, Reactive oxygen species, Hydrogen peroxide, Free-radical theory


Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals. In response to paraquat stress, young individuals generated more ROS and activated signaling pathways including p-ERK, p-AKT and p-AMPKα/β. After the initial response, young individuals then promoted NRF2 translocation and induced additional antioxidant enzymes and higher expression of phase II enzymes, including SOD, CAT, GPX, HO-1, GSTP-1and others, to maintain redox homeostasis. Moreover, young individuals also demonstrated a better ability to degrade damaged proteins by up-regulating the expression of chaperones and improving proteasome activity. Based on these data, we propose a new concept “Redox-stress Response Capacity (RRC)”, which suggests cells or organisms are capable of generating dynamic redox responses to activate cellular signaling and maintain cellular homeostasis. The decay of RRC is the substantive characteristic of aging, which gives a new understand of the redox theory of aging.

Concepts: Senescence, Antioxidant, Redox, Oxidative stress, Reactive oxygen species, Radical, Vitamin C, Free-radical theory


The theory stating that oxidative stress (OS) is at the root of several diseases is extremely popular. However, so far, no antioxidant is recommended or offered by healthcare systems neither approved as therapy by regulatory agencies that base their decisions on evidence-based medicine (EBM). This is simply because, so far, despite many preclinical and clinical studies indicating a beneficial effect of antioxidants in many disease conditions, randomised clinical trials have failed to provide the evidence of efficacy required for drug approval. In this review, we discuss the levels of evidence required to claim causality in preclinical research on OS, the weakness of the oversimplification associated with OS theory of disease and the importance of the narrative in its popularity. Finally, from a more translational perspective, we discuss the reasons why antioxidants acting by scavenging reactive oxygen species (ROS) might not only prevent their detrimental effects but also interfere with essential signalling roles. We propose that ROS have a complex metabolism and are generated by different enzymes at diverse sites and with different timing. Aggregating this plurality of systems in a single theory of disease may not be the best way to develop new drugs, and future research may need to focus on specific oxygen-toxifying pathways rather than on non-specific ROS scavengers. Finally, similarly to what is nowadays required for clinical trials, we recommend making unpublished data available in repositories (open data), as this will allow big data approaches or meta-analyses without the blinders of the publication bias.

Concepts: Antioxidant, The Canon of Medicine, Evidence-based medicine, Oxidative stress, Oxidative phosphorylation, Reactive oxygen species, Avicenna, Free-radical theory