What is the difference between an antioxidant and a prooxidant

The lack of dietary intake assessment does not allow us to determine the potential effects of the non-enzymatic dietary antioxidants intakes. It is of note however, that at least during chronic hypoxic exposure, exercise-induced enzymatic adaptations might be more efficient for reducing the systemic oxidative stress [ 25 ] than dietary antioxidant supplementation, which has previously been shown ineffective to alleviate HH induced oxidative stress [ 37 ].

It therefore seems unlikely that the diet could explain the observed differences in oxidative stress and antioxidant status. Although the participants were recruited at the same time of the yearly competitive cycle and did not seem to differ in their general health or performance status, this observation must be taken into account when interpreting these results.

While these measures represent a valid frame for assessment of systemic oxidative stress, they do not necessarily reflect the oxidative status in other tissues and organs [ 38 ]. This is the first study to date demonstrating different oxidative stress responses following two days LHTL protocols; one performed in normobaric hypoxia and one in hypobaric hypoxia. The obtained data suggest that hypobaric LHTL might result in significantly higher levels of oxidative stress compared to the normobaric LHTL of the same duration.

Higher oxidative stress levels following HH LHTL might be explained by the higher overall hypoxic dose and different physiological responses. Our data also suggest that hypoxia modulates oxidative stress in a dose dependent manner. These findings may have important implications for athletes, coaches and scientists employing different LHTL protocols since parameters of performance improvement following such training modalities are closely related to oxidative stress modulation.

The authors have no conflicts of interest, source of funding or financial ties to disclose and no current or past relationship with companies or manufacturers who could benefit from the results of the present study.

Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Data Availability: Due to legal restrictions imposed by the French government, data are accessible upon request from the Center of Research and Innovation on Sports and requests may be sent to Vincent Pialoux vincent.

Materials and Methods Ethics statement This study was part of a comprehensive research program investigating physiological, psychological and performance adaptions of endurance athletes to normobaric and hypobaric LHTL protocol. Participants Initially, twenty-seven highly trained male triathletes were recruited to participate in the study. Download: PPT. Table 1. Study design This cross-over designed study comprised of two main experimental campaigns.

Training quantification Two experienced coaches supervised all training sessions during the lead-in and the LHTL phases of the study. Fig 1. Table 2.

Fig 2. Fig 3. Conclusions This is the first study to date demonstrating different oxidative stress responses following two days LHTL protocols; one performed in normobaric hypoxia and one in hypobaric hypoxia. References 1. Int J Sports Med. Oxidative stress in humans during and after 4 hours of hypoxia at a simulated altitude of m. Aviat Space Environ Med. Ji LL. Exercise, oxidative stress, and antioxidants.

Am J Sports Med. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev. Catecholamine response during 12 days of high-altitude exposure 4, m in women. J Appl Physiol. Cellular reducing equivalents and oxidative stress.

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Dietary vitamin C and the risk for periodontal disease. J Periodontol ; This article has been cited by. Modulation of growth, immunity and antioxidant-related gene expressions in the liver and intestine of juvenile Sillago sihama by dietary vitamin C. Antiplasmodial activity of methanol leaf extract of Citrus aurantifolia Christm Swingle. Are polyphenol antioxidants at the root of medicinal plant anti-cancer success? Ion channels and transporters in adipose-derived stem cells.

Tahmina Monowar,Md. Scher M. Perinatal asphyxia: Timing and mechanisms of injury in neonatal encephalopathy. Curr Neurol Neurosci Rep. Effect of prenatal selenium supplementation on cord blood selenium and lipid profile. Pediatr Neonatol.

Bilirubin is an antioxidant of possible physiological importance. Hyperbilirubinemia results in reduced oxidative injury in neonatal Gunn rats exposed to hyperoxia. Free Radic Biol Med. Bilirubin and ascorbate antioxidant activity in neonatal plasma. FEBS Lett. Biomed Res Ther. Maisels MJ. Phototherapy--traditional and nontraditional. J Perinatol. Phototherapy causes DNA damage in peripheral mononuclear leukocytes in term infants. J Pediatr Rio J. The effect of exchange transfusion on prooxidant-antioxidant balance in newborns Jaundice.

Aycicek A, Erel O. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Mayer M. Association of serum bilirubin concentration with risk of coronary artery disease. Clin Chem. Neonatal blood plasma is less susceptible to oxidation than adult plasma owing to its higher content of bilirubin and lower content of oxidizable fatty acids. Pediatr Res. Neuzil J, Stocker R.

Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J Biol Chem. Increased expression of heme oxygenase-1 and bilirubin accumulation in foam cells of rabbit atherosclerotic lesions.

Arterioscler Thromb Vasc Biol. Stocker R. Antioxidant activities of bile pigments. Antioxid Redox Signal. Bilirubin and endothelial function. J Atheroscler Thromb. Inverse associations of bisphenol A and phthalate metabolites with serum bilirubin levels in Korean population.

Environ Sci Pollut Res Int. Diets rich in fruit and vegetables have been reported to exert a protective effect against a variety of diseases, particularly the cardiovascular disease and cancer [ 4 — 10 ].

The primary nutrients thought to provide protection afforded by fruit and vegetables are the antioxidants [ 11 , 12 ]. In an analysis, Potter [ 13 ] reviewed epidemiological studies, the majority of which showed a protective effect of increased fruit and vegetable intake and concluded that the high content of polyphenolic antioxidants in fruits and vegetables is probably the main factor responsible for the beneficial effects.

This awareness has led to a tremendous increase in the proportion of fruits and vegetables rich in antioxidant molecules on the dining table in the last two decades, but still the risk of chronic health problems refuses to decline, rather it upsurged with an enhanced vigour, giving rise to a very important question—why? If the health associated problems are due to oxidative stress and the dietary constituents are potent antioxidants, then the question of problem arrival should not be there.

What happens when these antioxidants reach the body tissues of interest or are there other factors still to be unrevealed? At that time, it was not accepted, but later on, after the famous address of Hans Selye at the prestigious College of France, it received approval among scientific community, but defining stress again troubled Selye over several years. Today, stress can be defined as a process of altered biochemical homeostasis produced by psychological, physiological, or environmental stressors [ 14 ].

Any stimulus, no matter whether social, physiological, or physical, that is perceived by the body as challenging, threatening, or demanding can be labeled as a stressor.

The presence of a stressor leads to the activation of neurohormonal regulatory mechanisms of the body, through which it maintains the homeostasis [ 14 ]. The overall physiological impact of these factors and the adaptation ability of the body determine the variations in growth, development, productivity, and health status of the animals [ 15 — 17 ].

These alterations can be viewed as a consequence of general adaptation syndrome as postulated by Hans Selye [ 18 ] and usually return to their normal status once the stimulus has disappeared from the scene. Strong and sustained exposure to stress [ 16 , 19 , 20 ] may result in higher energy negative balance and may ultimately result in reduction in adaptation mechanisms, increase in the susceptibility to infection by pathogens, decline in productivity, and finally a huge economical loss [ 16 , 19 , 21 ].

Many of us puzzle between distress, stress, and oxidative stress. Distress differs from stress, which is a physiological reaction that can lead to an adaptive response [ 22 ]. Distress is comparatively difficult to define and generally refers to a state in which an animal cannot escape from or adapt to the external or internal stressors or conditions it experiences resulting in negative effects upon its well-being [ 22 ].

Stress leads to adaptation but distress does not. Stress is a commonly used term for oxidative stress. Any alteration in homeostasis leads to an increased production of these free radicals, much above the detoxifying capability of the local tissues [ 23 ].

These excessive free radicals then interact with other molecules within cells and cause oxidative damage to proteins, membranes, and genes. In this process they often create more free radicals, sparking off a chain of destruction. Oxidative damage has been implicated in the cause of many diseases such as cardiovascular diseases, neuronal degeneration, and cancer and has an impact on the body's aging process too. An altered response to the therapeutic agents has also been observed [ 12 ]. External factors such as pollution, sunlight, and smoking also trigger the production of free radicals.

Most importantly, stress is one of the basic etiologies of disease [ 24 ]. It can have several origins like environmental extremes for example, cold, heat, hypoxia, physical exercise or malnutrition Figure 1.

On the basis of duration and onset, stress might be acute and chronic stress. The stress due to exposure of cold or heat is generally of acute type and is released with the removal of cause. Similarly, stress due to physical exercises or complete immobilization [ 25 ] is also acute in nature. The nutritional and environmental stresses, where the causes persist for a longer period of time, are chronic stress. The decrease in amplitudes is associated with inadequate ATP formation.

While changing perfusion of poststress isolated heart, myocardial rigidity further slows down and this seemed to be associated with activated glycolysis. There are no signs of cardiomyocytic lesion after cold stress. Reduced coronary flow is the only abnormal effect of acute cold stress under these conditions. High cardiac resistance to the damaging effect of cold is likely to be related to increased processes of glycolysis and glycogenolysis in the cardiomyocytes.

The activity of succinate dehydrogenase also gets elevated indicating the influence of cold stress on the Krebs cycle [ 27 ]. Coronary blood flow is also reduced and later on results in an altered basophils activity in the myocardium [ 28 ]. Health benefits of regular physical exercise are undebatable. Low physiological levels of ROS are generated in the muscles to maintain the normal tone and contractility, but excessive generation of ROS promotes contractile dysfunction resulting in muscle weakness and fatigue [ 29 ].

This is perhaps the reason why intense and prolonged exercise results in oxidative damage to both proteins and lipids in the contracting muscle fibers [ 30 ]. Regular exercise induces changes in both enzymatic and nonenzymatic antioxidants in the skeletal muscle. Furthermore, oxidants can modulate a number of cell signaling pathways and regulate the expression of multiple genes in eukaryotic cells. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels.

The magnitude of exercise-mediated changes in superoxide dismutase SOD activity of skeletal muscle increases as a function of the intensity and duration of exercise [ 31 , 32 ].

Chronic stress significantly alters limbic neuroarchitecture and function and potentiates oxidative stress [ 25 ] and emotionality in rats [ 34 ]. Chronic restraining of laboratory animals has been found to increase aggression, potentiate anxiety, and enhance fear conditioning [ 34 ]. Chronic immobilization induces anxiety behavior and dendritic hypertrophy in the basolateral amygdala, which persist beyond a recovery period.

Restraint of rats causes increased mucin release, as measured by [3H] glucosamine incorporation and goblet cell depletion, prostaglandin E2 PGE2 secretion, and mast cell activation in colonic explants [ 35 ]. Upregulation of the neurotensin precursor mRNA in the paraventricular nucleus of the hypothalamus after immobilization has also been reported [ 36 ]. Neurotensin stimulates mucin secretion from human colonic goblet cell line by a receptor mediated mechanism [ 37 ].

Nutrition is one of the most significant external etiologies for oxidative stress including its characteristics, type and quality, ratio of the various nutrients, dietary balance with regard to protein, carbohydrates, fats, macro- and trace elements, and so forth. Feed exercises a considerable influence over the physiological condition and thus the homeostasis of the animal body [ 16 , 19 , 38 — 42 ].

Feeding of endogenous or exogenous antioxidants can sensitively regulate glycolysis and the Warburg effect in hepatoma cells [ 43 ]. The leukocytosis with neutrophilia associated with fasting may be a consequence of an inflammatory reaction, caused by the direct action of ammonia on the rumen wall [ 38 , 44 ].

The monocytopenia may be a result of adaptation and defense mechanism undergoing in the body and leads to higher susceptibility to pathogens [ 21 , 45 ].

Nutritional stress causes adrenal gland hyperfunction and, thus, an increased release of catecholamines in the blood, with a simultaneous inhibition of the production of insulin in the pancreas [ 20 , 38 , 46 — 48 ]. The process of glycogenolysis is observed in the first 24 hours of fasting [ 20 , 39 , 46 — 49 ].

Thereafter, gluconeogenesis from amino acid precursors and lipolysis from glycerol, as well as from lactate through the Cori cycle, maintain a regular supply of glucose. Lactate gets transformed into pyruvate and participates in the gluconeogenesis along with the deaminated amino acids.

The increased production of catecholamines epinephrine and dopamine owing to fasting results in peripheral vasoconstriction and redistribution in blood which is expressed as erythrocytosis, leukocytosis, and neutrophilia [ 47 ]. Under hypoxic conditions, mitochondria participate in a ROS burst generated at complex III of the electron transport chain [ 50 ].

Hypoxia and reoxygenation result in reversible derangement of ATPase and architecture of mitochondrial membrane. Cardiac hemodynamic parameters, which decline immediately under hypoxic conditions, recover during reoxygenation [ 51 ], but the biochemical and histopathological studies provide a complicated pattern [ 52 ]. Furthermore, the number of ATPase particles visible at the inner aspect of mitochondrial membrane decreases.

ATPase activities fluctuate, retaining close contact with the membrane during hypoxia. The mitochondrial ultrastructural damage becomes more evident.

High-energy phosphates reserves of myocardium could help myocardial cells to maintain their structural integrity [ 52 ]. Each cell in the human body maintains a condition of homeostasis between the oxidant and antioxidant species [ 53 ]. Under conditions of normal metabolism, the continuous formation of ROS and other free radicals is important for normal physiological functions like generation of ATP, various catabolic and anabolic processes and the accompanying cellular redox cycles.

However, excessive generation of free radicals can occur due to endogenous biological or exogenous environmental factors, such as chemical exposure, pollution, or radiation. Superoxide is generated through either incomplete reduction of oxygen in electron transport systems or as a specific product of enzymatic systems, while NO is generated by a series of specific enzymes the nitric oxide synthases. Generally, mitochondria are the most important source of cellular ROS where continuous production of ROS takes place [ 55 ].

This is the result of the electron transport chain located in the mitochondrial membrane, which is essential for the energy production inside the cell [ 56 , 57 ]. Additionally, some cytochrome enzymes are also known to produce ROS [ 58 ]. Several endogenous cells and cellular components participate in initiation and propagation of ROS Table 1 [ 59 — 63 ]. All these factors play a crucial role in maintenance of cellular homeostasis. A stressor works by initiating any of these mechanisms.

Oxidative stress occurs when the homeostatic processes fail and free radical generation is much beyond the capacity of the body's defenses, thus promoting cellular injury and tissue damage. This damage may involve DNA and protein content of the cells with lipid peroxidation of cellular membranes, calcium influx, and mitochondrial swelling and lysis [ 60 , 63 , 64 ].

ROS are also appreciated as signaling molecules to regulate a wide variety of physiology. The role of hydrogen peroxide in promoting phosphatase inactivation by cysteine oxidation provided a likely biochemical mechanism by which ROS can impinge on signaling pathways [ 67 ]. The role of ROS in signaling of cytochrome c mediated apoptosis is also well established [ 68 ].

ROS can cause reversible posttranslational protein modifications to regulate signaling pathways. A typical example of the beneficial physiological role of free radicals is a molecule of nitric oxide NO.

NO can cause damage to proteins, lipids, and DNA either directly or after reaction with superoxide, leading to the formation of the very reactive peroxynitrite anion nitroperoxide ONOO— [ 73 — 75 ]. Lipid peroxidation of polyunsaturated lipids is one of the most preferred markers for oxidative stress.

In addition, the unsaturated aldehydes produced from these reactions have been implicated in modification of cellular proteins and other constituents [ 76 ]. The peroxidized lipid can produce peroxy radicals and singlet oxygen. Stress has a significant ecological and evolutionary role and may help in understanding the functional interactions among life history traits [ 77 — 79 ]. Stress leads to a number of physiological changes in the body including altered locomotor activity and general exploratory behavior.

The physiological role of ROS is associated with almost all of the body processes, for example, with reproductive processes [ 80 ]. Since under physiological conditions a certain level of free radicals and reactive metabolites is required, complete suppression of FR formation would not be beneficial [ 81 ]. Stress leads to activation of hypothalamic-pituitary-adrenal axis. The increased endogenous catecholamine release has been observed in cold environmental conditions. The activity of succinate dehydrogenase also gets elevated indicating the influence of ROS as evident in cold environmental conditions [ 27 ].

Coronary blood flow is reduced and an altered basophils activity in the myocardium is also observed [ 28 ]. Free radicals play an irreplaceable role in phagocytosis as one of the significant microbicidal systems [ 82 ], or in several biochemical reactions, for example, hydroxylating, carboxylating, or peroxidating reactions, or in the reduction of ribonucleotides [ 83 ].

At present, free radicals and their metabolites are assumed to have important biomodulating activities and a regulatory ability in signal transduction process during transduction of intercellular information [ 83 ]. Among the reactive oxygen species, H 2 O 2 best fulfills the requirements of being a second messenger [ 84 ].

Its enzymatic production and degradation, along with its functional requirement for thiol oxidation, facilitate the specificity for time and place that are required in signaling. Both the thermodynamic and kinetic considerations support that among different possible oxidation states of cysteine, formation of sulfenic acid derivatives or disulfides can be applicable as thiol redox switches in signaling. H 2 O 2 readily diffuses across biological membranes, and so it is well-suited as a diffusible messenger [ 85 , 86 ].

Increasing evidence indicates that H 2 O 2 is a particularly an intriguing candidate as an intracellular and intercellular signaling molecule because it is neutral and membrane permeable [ 84 , 87 ]. Each of these modifications modifies the activity of the target protein and thus its function in a signaling pathway.

Phosphatases appear to be susceptible to regulation by ROS in this manner, as they possess a reactive cysteine moiety in their catalytic domain that can be reversibly oxidized, which inhibits their dephosphorylation activity [ 67 ]. Any emotional stress leads to a decrease in sympathetic outflow as well as energy production of the tissues [ 27 ].

The harmful effect of free ROS and RNS radicals causing potential biological damage is termed oxidative stress and nitrosative stress, respectively [ 90 — 92 ]. Its impact on the organism depends on the type of oxidant, on the site and intensity of its production, on the composition and activities of various antioxidants, and on the ability of repair systems [ 93 ].

These ROS are generated as byproduct of normal aerobic metabolism, but their level increases under stress which proves to be a basic health hazard. Mitochondrion is the major cell organelle responsible for ROS production [ 50 , 57 ]. It generates ATP through a series of oxidative phosphorylation processes. Some metabolic diseases like diabetes are also associated with an enhanced level of lipoperoxidation Figure 2.

The central nervous system CNS is extremely sensitive to free radical damage because of a relatively small total antioxidant capacity. The ROS produced in the tissues can inflict direct damage to macromolecules, such as lipids, nucleic acids, and proteins [ ].

The polyunsaturated fatty acids are one of the favored oxidation targets for ROS. Once lipid peroxidation is initiated, a propagation of chain reactions will take place until termination products are produced. Therefore, end products of lipid peroxidation, such as malondialdehyde MDA , 4-hydroxynonenol 4-HNE , and F2-isoprostanes, are accumulated in biological systems. DNA bases are also very susceptible to ROS oxidation, and the predominant detectable oxidation product of DNA bases in vivo is 8-hydroxydeoxyguanosine.

These oxidative modifications lead to functional changes in various types of proteins enzymatic and structural , which can have substantial physiological impact.

Similarly, redox modulation of transcription factors produces an increase or decrease in their specific DNA binding activities, thus modifying the gene expression. Among different markers of oxidative stress, malondialdehyde MDA and the natural antioxidants, metalloenzymes Cu, Zn-superoxide dismutase Cu, Zn-SOD , and selenium dependent glutathione peroxidase GSHPx , are currently considered to be the most important markers [ — ].

Malondialdehyde MDA is a three-carbon compound formed from peroxidized polyunsaturated fatty acids, mainly arachidonic acid. It is one of the end products of membrane lipid peroxidation. Since MDA levels are increased in various diseases with excess of oxygen free radicals, many relationships with free radical damage were observed. Cu, Zn-SOD is an intracellular enzyme present in all oxygen-metabolizing cells, which dismutates the extremely toxic superoxide radical into potentially less toxic hydrogen peroxide.

Cu, Zn-SOD is widespread in nature, but being a metalloenzyme, its activity depends upon the free copper and zinc reserves in the tissues. GSHPx, an intracellular enzyme, belongs to several proteins in mammalian cells that can metabolize hydrogen peroxide and lipid hydroperoxides. The relationship between oxidative stress and immune function of the body is well established. The immune defense mechanism uses the lethal effects of oxidants in a beneficial manner with ROS and RNS playing a pivotal role in the killing of pathogens.

The skilled phagocytic cells macrophages, eosinophils, heterophils , as well as B and T lymphocytes, contain an enzyme, the nicotinamide adenine dinucleotide phosphate NADPH oxidase [ , ], which is responsible for the production of ROS following an immune challenge. At the onset of an immune response, phagocytes increase their oxygen uptake as much as 10—20 folds respiratory burst.

Although the use of these highly reactive endogenous metabolites in the cytotoxic response of phagocytes also injures the host tissues, the nonspecificity of these oxidants is an advantage since they take care of all the antigenic components of the pathogenic cell [ ]. Several studies have demonstrated the interdependency of oxidative stress, immune system, and inflammation. Increased expression of NO has been documented in dengue and in monocyte cultures infected with different types of viral infections.

Increased production of NO has also been accompanied with enhancement in oxidative markers like lipid peroxidation and an altered enzymatic and nonenzymatic antioxidative response in dengue infected monocyte cultures [ ]. Moreover, it has been revealed that reduced NADPH oxidase is present in the pollen grains and can lead to induction of airway associated oxidative stress. Such oxidative insult is responsible for developing allergic inflammation in sensitized animals.

There is triggering of production of interleukin IL -8 along with proinflammatory cytokines, namely, tumor necrosis factor TNF -alpha and IL There is initiation of dendritic cell DC maturation that causes significant upregulation of the expression of cluster of differentiation CD , 86 and 83 with a slight overexpression of CD in the membrane.

So altogether, innate immunity locally may be alleviated due to oxidative stress induced by exposure to pollen. This in turn helps in participation to initiate adaptive immune response to pollen antigens [ ]. The immune status directly interplays with disease production process. The role of physical and psychological stressors contributes to incidences and severity of various viral and bacterial infections.

Fatal viral diseases produce severe oxidative stress OS leading to rigorous cellular damage. However, initiation, progress, and reduction of damages are governed by the redox balance of oxidation and antioxidation.

The major pathway of pathogenesis for cell damage is via lipid peroxidation particularly in microsomes, mitochondria, and endoplasmic reticulum due to OS and free radicals [ , ].

All the factors responsible for the oxidative stress directly or indirectly participate in immune system defense mechanism. Any alteration leading to immunosuppression can trigger the disease production Table 2. Oxidative stress can induce production of free radicals that can modify proteins. Alterations in self-antigens i. The end products of these reactions may be stable molecules such as 3-chlorothyrosine and 3-nitrotyrosine that may not only block natural biotransformations of the tyrosine like phosphorylation but also change the antigenic profile of the protein.

The oxidative modification of the proteins not only changes the antigenic profile of latter but also enhances the antigenicity as well [ ]. Moreover, oxidative stress poses an additional threat to the target tissues as in the case of insulin-producing beta cells in the islet of Langerhans [ ]. To add to this, autoimmune diseases often occur only in a single tissue irrespective of the fact that other tissues also contain the same antigen but perhaps lack the level of oxidative stress required to initiate the process.

This pathological autoreactivity targeted towards redox-modified self-antigens and diagnostic assays designed to measure its cross-reactivity to normal self-antigens further complicate the detection of autoimmune diseases [ ].

In the development of autoimmune disease pathogenesis, there is possibly role of psychological stress along with major hormones that are related to stress.

It is thereby presumed that the neuroendocrine hormones triggered by stress lead to dysregulation of the immune system ultimately resulting in autoimmune diseases by alteration and amplification of production of cytokine [ ].

All pathogens, irrespective of their classification, bacterial, viral, or parasitic, with impaired antioxidant defenses show increased susceptibility to phagocytic killing in the host tissues, indicating a microbicidal role of ROS [ 80 ]. Vice versa to this, different studies have proven that individuals deficient in antioxidative mechanism are more susceptible to severe bacterial and fungal infections as in case of HIV infections [ ]. Reactive species are important in killing pathogens but as a negative side effect can also injure the host tissues immunopathology.

This is particularly apparent during chronic inflammation, which may cause extensive tissue damage with a subsequent burst in oxidative stress [ ]. The production of free radicals involves macrophages and neutrophils to combat the invading microbes.

The whole of the process is performed in host cells during the activation of phagocytes or the effect of bacteria, virus, parasites, and their cell products reactivity with specific receptors. These cellular damages in general lead to altering immune response to microbes and ultimately altered susceptibility to bacterial, viral, and parasitic infections [ ].

Carcinogenesis can be defined as a progressive erosion of interactions between multiple activating and deactivating biological activities both immune and nonimmune of host tissue resulting in progressive loss of integrity of susceptible tissues. The primitive steps in development of cancer, mutation, and ageing are the result of oxidative damage to the DNA in a cell.

A list of oxidized DNA products has been identified currently which can lead to mutation and cancer. Alongside with ROS other redox metals also play a critical role in development of ageing, mutation, and tumour [ ]. In regular cellular mechanism, free radicals scavenger vitamin E, C and glutathione along with enzymes like catalase, peroxidases, and superoxide dismutase control the mechanism of DNA repair.

Irregular repair or absence of repair of damaged DNA due to OS might lead to mutagenesis and genetic transformation along with alteration in apoptotic pathway [ ]. Oxidative stress produced due to unresolved and persistent inflammation can be a major factor involved in the change of the dynamics of immune responses. These alterations can create an immunological chaos that could lead to loss of architectural integrity of cells and tissues ultimately leading to chronic conditions or cancers [ ].

Oxidative stress is reported to be the cause of induction of allergies, autoimmune or neurodegenerative diseases along with altered cell growth, chronic infections leading to neoplasia, metastatic cancer, and angiogenesis [ ]. Damage to the cellular components such as proteins, genes, and vasculature is behind such alterations. Moreover, further accumulation of confluent, useless, and complex cells causes additional oxidative stress and maintains continuous activation of immune system and unanswered inflammation [ ].

Tissue necrosis and cellular growth are stimulated by coexpression of inflammatory mediators due to oxidative stress-induced altered activity of the cells of the immune system. Such changes of tissue function are mainly responsible for autoimmune, neurodegenerative, and cancerous conditions [ , ]. Various factors produced due to oxidative stress along with excessively produced wound healing and apoptotic factors, namely, TNF, proteases, ROSs, and kinases, actively participate in tumor growth and proliferation.

These factors are also required for the membrane degradation, invasion of neighboring tissues, and migration of tumor cells through vasculature and lymphatic channels for metastasis [ — ].

The incidences of thyroid cancers have increased in the last decades worldwide which is most likely due to exposure of human population in mass to radiation causing increased free radical generation [ ]. Aging is an inherent mechanism existing in all living cells. There is a decline in organ functions progressively along with the age-related disease development.