European Journal streess Biochemistry : — Anoxic stress leads to hydrogen Antioxidant and oxidative stress formation in plant cells. Reviewed by: Kai HuUniversity Hospital Würzburg, Germany Jun RenUniversity of Washington, United States. Yi, H.

Antioxidant and oxidative stress -

The Nutrition Source Menu. Search for:. Home Nutrition News What Should I Eat? In , a rating tool called the Oxygen Radical Absorbance Capacity ORAC was created by scientists from the National Institute on Aging and the United States Department of Agriculture USDA.

It was used to measure the antioxidant capacity of foods. The USDA provided an ORAC database on its website highlighting foods with high ORAC scores, including cocoa, berries, spices, and legumes. Blueberries and other foods topping the list were heavily promoted in the popular press as disease-fighters even if the science was weak, from cancer to brain health to heart disease.

However, 20 years later the USDA retracted the information and removed the database after determining that antioxidants have many functions, not all of which are related to free radical activity.

Although this was not a primary endpoint for the trial, it nevertheless represents an important outcome. In the Heart Outcomes Prevention Evaluation HOPE trial, the rates of major cardiovascular events were essentially the same in the vitamin E A recent trial of vitamin E in Israel, for example, showed a marked reduction in coronary heart disease among people with type 2 diabetes who have a common genetic predisposition for greater oxidative stress.

In the Supplementation en Vitamines et Mineraux Antioxydants SU. MAX study, 13, French men and women took a single daily capsule that contained mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, mcg selenium, and 20 mg zinc, or a placebo, for seven and a half years. The vitamins had no effect on overall rates of cardiovascular disease.

Lung disease A study from the Journal of Respiratory Research found that different isoforms of vitamin E called tocopherols had opposing effects on lung function. Cancer When it comes to cancer prevention, the picture remains inconclusive for antioxidant supplements.

MAX randomized placebo-controlled trial showed a reduction in cancer risk and all-cause mortality among men taking an antioxidant cocktail low doses of vitamins C and E, beta-carotene, selenium, and zinc but no apparent effect in women, possibly because men tended to have low blood levels of beta-carotene and other vitamins at the beginning of the study.

Age-related eye disease A six-year trial, the Age-Related Eye Disease Study AREDS , found that a combination of vitamin C, vitamin E, beta-carotene, and zinc offered some protection against the development of advanced age-related macular degeneration, but not cataracts, in people who were at high risk of the disease.

However, relatively short trials of lutein supplementation for age-related macular degeneration have yielded conflicting findings. The study found that people taking the vitamins were less likely to progress to late-stage AMD and vision loss.

However, the study authors noted that taking lutein and zeaxanthin alone or vitamin E alone did not have a beneficial effect on these eye conditions. The Selenium and Vitamin E Cancer Prevention Trial SELECT Eye Endpoints Study, which followed 11, men for a mean of five years, did not find that vitamin E and selenium supplements, in combination or alone, protected from age-related cataracts.

It did not find that antioxidant supplements of vitamin E or selenium, alone or in combination, protected against dementia compared with a placebo. Early death A meta-analysis of 68 antioxidant supplement trials found that taking beta-carotene and vitamin A and E supplements increased the risk of dying.

It was also difficult to compare interventions because the types of supplements, the dosages taken, and the length of time they were taken varied widely. The same authors conducted another systematic review of 78 randomized clinical trials on antioxidant supplements including beta-carotene, vitamin A, vitamin C, vitamin E, and selenium alone or in combination.

The study found that both people who were healthy and those with diseases taking beta-carotene and vitamin E supplements had a higher rate of death.

The duration of the studies varied widely from one month to 12 years, with varying dosages. The first inkling came in a large trial of beta-carotene conducted among men in Finland who were heavy smokers, and therefore at high risk for developing lung cancer.

The trial was stopped early when researchers saw a significant increase in lung cancer among those taking the supplement compared to those taking the placebo. Again, an increase in lung cancer was seen in the supplement group.

MAX trial, rates of skin cancer were higher in women who were assigned to take vitamin C, vitamin E, beta-carotene, selenium, and zinc. These results came from the Selenium and Vitamin E Cancer Prevention Trial SELECT that followed 35, men for up to 12 years. References National Center for Complementary and Integrative Health NCCIH.

Antioxidants: In Depth. Carlsen MH, Halvorsen BL, Holte K, Bøhn SK, Dragland S, Sampson L, Willey C, Senoo H, Umezono Y, Sanada C, Barikmo I. The total antioxidant content of more than foods, beverages, spices, herbs and supplements used worldwide.

Nutrition journal. Semba RD, Ferrucci L, Bartali B, Urpí-Sarda M, Zamora-Ros R, Sun K, Cherubini A, Bandinelli S, Andres-Lacueva C. Resveratrol levels and all-cause mortality in older community-dwelling adults.

JAMA internal medicine. Grodstein F, Kang JH, Glynn RJ, Cook NR, Gaziano JM. Archives of internal medicine. USDA Oxygen Radical Absorbance Capacity ORAC of Selected Foods, Release 2 Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE.

Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, Dagenais GR. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial.

GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. The Lancet. Milman U, Blum S, Shapira C, Aronson D, Miller-Lotan R, Anbinder Y, Alshiek J, Bennett L, Kostenko M, Landau M, Keidar S.

Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin genotype: a prospective double-blinded clinical trial. Arteriosclerosis, thrombosis, and vascular biology. Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, Belanger C, LaMotte F, Gaziano JM, Ridker PM, Willett W.

Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. New England Journal of Medicine. Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, Roussel AM, Favier A, Briançon S.

The SU. In CVD, gene expression is altered due to oxidative stress. Increased ROS levels modulate transcription factor activity, especially NF-κB, activator protein-1 AP-1 and the peroxisome proliferators-activated receptor PPAR family of transcriptional activators Elahi et al.

As a result of increasing ROS generation, one of the first events in atherogenesis, as well as in other CVDs correlated with endothelial dysfunction, is the oxidative modification of low-density lipoprotein LDL Singh et al. Indeed, both cell membranes and LDL, enriched with phospholipids, are highly sensitive to oxidative modification.

Oxidized phospholipids, through receptor-mediated or receptor-independent pathways, can therefore then activate endothelial cells, induce endothelium adhesion molecules expression, attract monocytes, have endothelium cytotoxic effects, and increase proinflammatory gene activity and cellular growth factors Esper et al.

All of these processes provoke endothelial dysfunction, platelet aggregation, and metalloproteinase expression and favor thrombogenesis Esper et al. In atherosclerotic plaque, increased matrix metalloproteinase expression and activity triggered by oxidative stress lead to its rupture and consequent thrombosis He and Zuo, The NF-κB activity in atherosclerosis is mainly due to oxidized LDL Singh et al.

At the same time, upregulated NF-κB is detected in smooth muscle cells, endothelial cells, macrophages and T cells of atherosclerotic plaques Mach et al. In the blood vessel wall, all layers can produce ROS under pathological conditions, and most of them are primarily derived from NOX Reid, Due to increased ROS levels, NO bioavailability is decreased, and consequently, endothelium-dependent relaxation is reduced Chen J.

Cardiac myocytes have a more significant number of mitochondria than other cells and use higher oxygen levels for energy production in the form of ATP. In myocytes, ROS trigger cardiac injury, both oxidizing essential proteins for excitation-contraction and decreasing NO bioactivity Hare and Stamler, Furthermore, oxidative stress produced in mitochondria induces mitochondrial DNA mtDNA damage and leads to CVD.

In myocardial ischemia, hypoxia and reoxygenation trigger an increase in free radical production in cardiac tissue Elahi et al. ROS produced during reoxygenation cause direct oxidative damage to cellular components and lead to indirect damage through the activation of localized inflammation Gutteridge and Halliwell, In heart failure, excessive ROS production is based on increased activity of XOR and NOX Battelli et al.

Increased ROS production is a consequence of prolonged endoplasmic reticulum stress and mitochondrial-derived oxidative stress in cardio-metabolic disorders. Furthermore, some disturbance in these organelles activates signaling pathways that alter cardiac ion channels function or expression, involved in the generation of an action potential that promotes arrhythmogenesis Tse et al.

The administration of cytostatics to humans is followed by cardiotoxicity due to increased plasma levels of ROS and lipid peroxidation products and decreased plasma and tissue levels of antioxidants. Myocardial changes that occur after treatment include: myocyte loss through apoptosis or necrosis, loss of myofibrils, distension of the sarcoplasmic reticulum, and mitochondrial ballooning.

Recent studies on transgenic mice have shown that in cardiotoxicity induced by Doxorubicin, free radicals can be counteracted by metallothionein and liensinine Kang, ; Liang et al.

Cancer development in humans is a complex process that includes cellular and molecular changes mediated by various endogenous and exogenous stimuli Docea et al.

It has been established that oxidative DNA damage is one of the key characteristics of carcinogenesis Smith et al. Cancer initiation and promotion are associated with chromosomal defects and activation of oncogenes by free radicals Glasauer and Chandel, A common form of injury is the formation of hydroxylated DNA bases, considered an important event in chemical carcinogenesis.

They interfere with healthy cell growth by causing genetic mutations and altering normal gene transcription. Oxidative lesions also produce many changes in the structure of DNA Li et al.

ROS involvement in a different stage of carcinogenesis has been shown in various model systems. Excessive amounts of these free radicals can lead to cell damage and apoptosis. Many forms of cancer are considered to be the result of free radicals and DNA reactions, leading to mutations that can affect the cell cycle and lead to neoplasia Pizzino et al.

ROS overproduction has an impact on cancer cell proliferation, metastatic potential, and it is associated with invasiveness and poor prognosis Liou et al.

ROS contributes to cancer cell migration through various mechanisms: i matrix degradation, ii cell-cell contact, iii cytoskeleton remodeling, regulation of gene expression, iv invadopodia formation Pizzino et al. For example, mitochondria-derived ROS has an impact on initial extracellular matrix contact, NOX-derived ROS are involved in invadopodia formation.

At the same time, ROS increase in cytosol plays a significant role in cytoskeleton remodeling Herrera et al. The effect of ROS on cancers depends on the type of organ, as well as on the grade of disease progression.

Skin carcinogenesis and exposure to UVA: the ultraviolet component A sunlight UV-A with the wavelength — nm has the potential to generate oxidative stress in cells and tissues, so that endogenous and exogenous antioxidants strongly influence the biological effects of UVA Sage et al.

The physiological doses of UVA determine the expression of some genes collagenase, hem oxygenase-1, and nuclear oncogenes , whose effects can be significantly increased by removing intracellular GSH or by increasing the lifetime of molecular oxygen.

Repeated exposure of human skin to UV radiation leads not only to skin carcinogenesis but also to photo-aging through DNA damage Cortat et al. Hydroxyl radicals can bind to DNA and produce 8-OH deoxyguanosine 8-OHdG , which consequently increases the risk of mutation.

Additionally, increased cancer cell proliferation requires high ATP levels that lead to ROS accumulation, particularly at initial stages of cancer genesis. In cancer cells, there is the condition of constant oxidative stress induced by mitochondrial dysfunction and metabolic changes.

In fact, under normal circumstances, increased ROS levels stimulate cell death, but cancer cells overcome that by activating numerous oncogenes, which then induce nuclear factor erythroid 2-related factor 2 NRF2 expression.

NRF2 is the primary regulator of cell survival that raises cancer progression by protecting cancer cells from ROS and DNA damage Jaramillo and Zhang, ROS are implicated in cancer progression, promoting cyclin D1 expression, extracellular signal-regulated kinase ERK and JUN N-terminal kinase JNK phosphorylation, and MAPK activation Saha et al.

However, cancer cells enable proliferation, avoiding ROS-induced apoptosis, despite high mutagenesis. In neoplastic disorders, ROS promote protein oxidation and lipid peroxidation. Moreover, ROS trigger toxic protein carbonyls formation which has a significant impact on other proteins or lipids Benfeitas et al.

In addition, as a result of lipid peroxidation, cancer cells accumulate products, such as 4-hydroxynon-enal, one of the most studied products of phospholipid peroxidation, owing to its reactivity and cytotoxicity. In the brain, not all neuronal groups are equally sensitive to oxidative stress.

For instance, neurons with longer axons and multiple synapses require more energy for axonal transport or long-term plasticity Salehi et al. High ATP demand, in combination with dysfunctional mitochondria, make these neuron groups more sensitive to degeneration Wang and Michaelis, Correctly, dopaminergic neurons are exposed to additional oxidative stress produced by the dopamine metabolism, generating H 2 O 2 and dopamine autoxidation, which generates superoxide Delcambre et al.

During aging, mutations in mtDNA accumulate, cytosolic calcium dysregulates, and ETC function decreases, making aging one of the major risk factors contributing to neurodegeneration Payne and Chinnery, The oxidized molecules of DNA, proteins and lipids found in the brain tissue of post-mortem patients with neurodegenerative disorders highlight the role of oxidative stress in these diseases Sharifi-Rad M.

Another cause of neurodegenerative diseases is a defective use of metals by the brain, by the intervention of mutant proteins, formed as a result of oxidative stress Niedzielska et al.

In the case of Alzheimer disease, a protein called amyloid beta Aβ , consisting of 40 amino acid residues, is present in all the cells of the body, under normal, harmless and even beneficial conditions, as it is a natural antioxidant Danielson and Andersen, ; Li et al.

One explanation is the accumulation in the brain of a modified form of the Ab protein consisting of 42 amino acid residues , which fails to properly bind metals, promotes oxidative processes; by reacting in self-defense, neurons produce antioxidants in increased quantities, including the modified form of the Aβ protein, which thus becomes an antioxidant pro-oxidant, amplifying oxidative disasters by initiating chain reactions Danielson and Andersen, Mutations of the superoxide dismutase 1 SOD1 protein have been linked to another neurodegenerative disease that affects motility familial amyotrophic lateral sclerosis Huai and Zhang, In its unmodified form, SOD1 is a natural antioxidant that prevents the formation of peroxide anion as a dangerous reactive form of oxygen Saccon et al.

The mutant forms of this protein fixate a much smaller amount of metals than the usual form, which results in the formation of an excess of peroxynitrite ONOO — affecting the motor neurons required for normal functioning, causing severe motor disorders Pasinelli et al. The excessive use of glucose for energy production makes the brain especially susceptible to oxidative stress, and mitochondrial ETC is the primary ROS source Cobley et al.

Most of the ROS present in the brain derive from mitochondrial ETC complex I and III ETC I and III , as O 2 — by-products Andreyev et al.

Indeed, the main targets for mitochondria-generated ROS are mitochondrial permeability transition pore MPTP , poly ADP-ribose polymerase PARP , and mtDNA Gandhi and Abramov, Other oxidant sources arise from NADPH oxidase, present in astrocytes, microglia and neurons, while NOS inhibition has shown neuroprotective effects Abramov et al.

In the pathogenesis of neurodegeneration, many processes are included, such as protein misfolding and aggregation, abnormal kinase-signaling pathways, neuronal calcium dysregulation, and even impaired synaptic transmission Gandhi and Abramov, Mechanisms of action of ROS: these affect proteins by modifying them in oxidative forms, which tend to form aggregates Blokhuis et al.

Protein aggregates then inhibit proteasomes, the main organelles in the cell for degradation of abnormal proteins Chen et al. Accumulation of modified proteins with an inability to be destroyed in the proteasome stimulate more ROS formation and form a vicious cycle, a phenomenon included in neurodegenerative diseases related to oxidative stress Chen et al.

Many metabolic contexts can lead to conditions of oxidative stress. A condition in which oxidation is an important pathogenetic link is type 2 diabetes. In this disease, insulin resistance is the basic component, to which a compensatory hypersecretion of insulin is linked.

Reactive oxygen species can induce inactivation of signaling mechanisms between insulin receptors and the glucose transport system, leading to insulin resistance Chen X. On the other hand, diabetes itself is a generator of oxidative stress, with atherogenetic consequences. Hyperglycemia induces the generation of superoxide ions in endothelial cells at the mitochondrial level.

In diabetes, electron transfer and oxidative phosphorylation are decoupled, resulting in the production of superoxide anions and inefficient ATP synthesis. Therefore, preventing the damage caused by oxidation is a therapeutic strategy in diabetes.

Increased levels of free fatty acids with consecutive accumulation of intramyocellular lipids were thought to be the cause of insulin resistance and beta-pancreatic cell death. Studies have shown that both glucose and free fatty acids can initiate the formation of free radicals through mitochondrial mechanisms and NADPH oxidase in muscles, adipocytes, beta cells and other cell types.

Free fatty acids penetrate cellular organs, including mitochondria, where high levels of reactive oxygen species can cause peroxidation and damage. Recent studies show that type II diabetes and insulin resistance are associated with a decrease in mitochondrial oxidative function in skeletal muscle.

Moreover, in this type of diabetes, the mitochondria are smaller, rounder and more likely to produce superoxide. Disorders of the mitochondrial transport chain, excessive generation of reactive species and lipoperoxides, as well as decreases in antioxidant mechanisms have also been observed in diabetes and obesity.

Diabetes has a number of complications over time, of which macrovasculopathy is very important. The increase in cardiovascular risk in patients with diabetes can be explained by the association between diabetes hypertension, dyslipidemia and coronary atherosclerotic disease.

However, other mechanisms are also involved, such as the effects of hyperglycemia on endothelial function, the effects of glucose and fatty acids on myocardial cells, at the structural level but also of gene expression Aroor et al. Diabetic cardiovascular complications are caused by impaired cardiac microvascular function.

In addition to the structural and functional changes that occur in diabetic cardiomyopathy, other mechanisms can be targeted pharmacologically.

Sodium-glucose co-transporter-2 SGLT2 inhibitors are the first class of antidiabetic drugs that have reduced the risk of heart failure in type 2 diabetes Karam et al. Empagliflozin has an indication to reduce cardiovascular mortality in patients with diabetes and atherosclerotic disease.

A recent study demonstrated the beneficial effect of empagliflozin on cardiac microvascular injury in diabetes and the protective mechanism against oxidative stress in mitochondria Zhou et al. Another recent study showed that aminoguanidine has a beneficial effect on diabetes-induced heart abnormalities.

Aminoguanidine saves contractile abnormalities and diabetes-induced cardiac remodeling. This was explained by inhibition of endoplasmic reticulum stress and induction of autophagy Pei et al.

Insulin resistance, abdominal obesity, atherogenic dyslipidemia, endothelial dysfunction, high blood pressure, hypercoagulability, genetic predisposition and chronic stress are the main factors underlying the metabolic syndrome.

Metabolic syndrome is often characterized by oxidative stress, a condition in which there is an imbalance between the production and inactivation of reactive oxygen species. Increased generation of reactive oxygen species, decreased activity of antioxidant systems or both mechanisms may be involved in the occurrence of oxidative stress Karam et al.

A study showed that lenalidomide attenuates oxidative cardiovascular tissue damage and apoptosis in obese mice by inhibiting tumor necrosis factor Zhu et al. This accumulation of losses in cells would be the reason for aging and aging-associated degenerative diseases Tsoukalas et al.

Aging can be caused by both genetic and external factors, such as incorrect diet, improper physical exercise, chronic drug use, untreated inflammatory conditions, smoking, and alcohol abuse.

Today, while there are several theories of aging, the basic principle of most of them is still oxidative stress Finkel and Holbrook, ; Payne and Chinnery, The major systems involved in overproduction of oxidative stress in cells are mitochondria and NOX Bedard and Krause, In the aging process, it has been noticed that high-molecular protein aggregates accumulate in cells Davalli et al.

Predominantly, these aggregates are made from proteins, with the remainder consisting of various lipids Barrera, ; Takalo et al. Thus, the crucial point for protein homeostasis maintenance is the degradation of these aggregates.

The central place for cell damaged protein degradation is the proteasome, which recognizes only unfolded proteins as degradation targets Saez and Vilchez, Proteasome inhibition prevents further degradation of newly formed oxidized proteins and increases protein aggregation formation in cells Takalo et al.

Besides that, proteasome becomes dysfunctional during aging. While proteasomal dysfunction is correlated with age progression and protein aggregation, proteasome activation slows the aging progress down and increases longevity Chondrogianni et al.

In many invertebrate models and cell lines, it has been shown that the overexpression of different proteasomal regulatory or catalytic subunits or treatment with specific compounds has positive effects on proteasome activity Saez and Vilchez, Recently, most of the data have indicated that antioxidant supplementation does not decrease the incidence of age-related diseases Schottker et al.

Antioxidants break radical chain reactions, preventing oxidative stress-related damage Da Pozzo et al. Figure 2. Schematic figure of the link between ROS, oxidative stress and their effects on the human body.

Alteration of chemical reactions at the cellular level leads to the appearance of free radicals and peroxides that affect the intracellular structures — proteins, lipids, DNA, with the disruption of intrinsic mechanisms at this level.

Free radicals are normally produced in the body due to the influence of external factors, such as pollution, cigarette smoke, or internal, due to intracellular metabolism when antioxidant mechanisms are exceeded. Their role requires acting both in hydrophilic and hydrophobic cellular environments, so their chemical structure is quite heterogeneous.

There are enzymatic and non-enzymatic antioxidants Banafsheh and Sirous, , as shown in Figure 1. but, from a nutritional perspective, a more informative classification can be made between endogenous and exogenous classes.

The first class comprises all antioxidants that cells can synthesize from smaller building blocks. Accordingly, all enzymatic antioxidants are endogenous, as well as some non-enzymatic ones i. Figure 3. Primary enzymes SOD or peroxidases act directly in scavenging ROS.

Secondary enzymes, such as glutathione reductase and glucosephosphate dehydrogenase, support the action of primary enzymes regenerating NAPDH and reduced glutathione. On the contrary, exogenous antioxidants have to be ingested through the diet, since their synthesis is impossible in eukaryotic cells.

So, particular attention should be paid on this latter class, since this is the most unpredictable component in cellular redox balance.

Antioxidants can be divided into two categories depending on their solubility: water soluble and liposoluble Lazzarino et al. Water soluble antioxidants are best absorbed in the body because the vegetables and fruits that contain such antioxidants, also contain water.

On the other hand, they are rapidly eliminated from the body through the urine. Water-soluble antioxidants include polyphenols, but also vitamin C Lazzarino et al. Liposoluble antioxidants, fat-soluble antioxidants are those that are absorbed in the presence of fats.

Therefore, in the absence of fats, the body cannot absorb and use these antioxidants. It is important to note, however, that they are not easily removed from the body and can accumulate over time, exceeding the healthy level.

Vitamin E is an example of a fat-soluble antioxidant Lazzarino et al. This is the case, for instance, for glucosephosphate dehydrogenase that regenerates NADPH, essential for primary enzyme action Figure 2.

Primary enzymes act directly on the main ROS arising from incomplete O 2 reduction, O 2 — and H 2 O 2. SOD scavenges the former, whereas CAT and GPX remove the latter. SOD E. In turn, H 2 O 2 can be removed by the other enzymatic antioxidant systems. SODs can be divided into four groups, with different metal cofactors.

Copper-zinc SOD is most abundant in chloroplasts, cytosol and extracellular space. Iron SOD is found in plant cytosol and in microbial cells, whereas manganese SODs are mitochondrial Perera et al.

SOD also competes for superoxide anion with NO. Therefore, SOD also indirectly reduces the formation of another deleterious ROS, peroxynitrite ONOO — , reaction 2 , and increases the NO biological availability, an essential modulator for endothelial function. CAT E. CAT is mainly located in peroxisomes, and despite being ubiquitous, the highest activity is present in liver and red blood cells.

CAT works with a two-step mechanism, somewhat resembling the formation in the first step of a peroxidase-like compound I intermediate, CpdI reaction 4 Alfonso-Prieto et al. A NADPH molecule is bound to each subunit, minimizing H 2 O 2 —mediated inactivation []. CAT is one of the enzymes with the highest known k cat more than 10 6 s —1 in all known proteins, close to a diffusion-controlled reaction Tovmasyan et al.

GPX E. The GPX family is composed of eight isoenzymes GPX Each enzyme presents peculiar features. GPX1, 2, 3, and 4 incorporate selenocysteine a non-standard amino acid, where the sulfur atom of cysteine is replaced by selenium. During the catalytic cycle, selenocysteine is converted from selenol Enz-SeH to selenenic acid Enz-SeOH , with concomitant reduction of H 2 O 2 or ROOH.

Then, the first GSH molecules yield selenenyl sulfide intermediate Enz-Se-SG. An incoming second GSH molecule attacks Enz-Se-SG, regenerating the enzymatic resting form Enz-SeH, releasing the oxidized and dimerized GSSG Cardoso et al.

Another important class of enzymatic peroxide scavenger is PRDX. Six different classes of PRDX have been identified Poole and Nelson, , showing either one 1-Cys PRDX or two 2-Cys PRDX redox-active cysteine residues Park et al. The PRDX catalytic cycle involves H 2 O 2 decomposition and the subsequent regeneration of the resting enzyme, using a small cysteine protein thioredoxin Trx as the reductant reactions 8 and 9.

Trx shows two vicinal cysteines in the typical CXXC motif , forming, in turn, a disulfide internal bridge upon oxidation. In the case of PRDX6 isoform, Trx can be replaced by GSH. All the enzymatic activities described above rely on the continuous regeneration of the reduced form of reductants mainly GSH and Trx.

This is usually performed by some reductases, NADPH-dependent such as glutathione reductase E. However, as shown in Figure 2 , reduced NADPH is, in turn, needed by these reductases for their continuous action.

So, enzymes responsible for the constant NADPH production can be considered secondary antioxidants, as their misfunction could affect the whole ROS balance. The main NADPH metabolic source is the pentose phosphate pathway, through the first two enzymatic activities: glucosephosphate dehydrogenase E.

However, other contributions come from the malic enzyme E. Some chemical molecules of low-molecular-weight can also directly act as antioxidants. In this case, their action is not catalytic, always needing antioxidant regeneration or its supply from the diet.

Non-enzymatic antioxidants can therefore be divided into endogenous if the eukaryotic cell is able to synthesize it and exogenous if the antioxidant needs to be ingested mandatorily through the diet. GSH γ-glutamyl-cysteinyl-glycine, Figure 4 is a tripeptide, mainly distributed in cytosol, but also in nuclei, peroxisomes and mitochondria.

Despite being ubiquitous, the liver is the leading site for its synthesis Banafsheh and Sirous, GSH biosynthesis is an endergonic process ATP hydrolysis is coupled , in which firstly glutamate and cysteine condense to yield γ-glutamylcysteine reaction catalyzed by glutamate-cysteine ligase, E.

This unusual γ-peptidic bond protects it from the common peptidases action. In the final step, GSH synthetase E. Figure 4. Glutathione GSH , a tripeptide with an active —SH function.

GSH undergoes a redox cycle, dimerizing with a disulfide bridge formation. α-Lipoic acid 1,2-dithiolanepentanoic acid, Figure 4 is a disulfide compound that undergoes a redox cycle similar to GSH.

Accordingly, it scavenges reactive ROS, and regenerate vitamins C and E, and GSH in their active forms Kucukgoncu et al. Lipoic acid also has a role in metal chelation, preventing Fenton-like radical reactions Zhang and McCullough, Nevertheless, even small proteins, such as Trx and glutaredoxin can similarly function as thiol antioxidants, showing redox-active mono- or di-cysteine motif CXXC.

Both proteins can be in turn reduced back to their active form, directly by GSH or indirectly by NADPH Banafsheh and Sirous, Melatonin N -acetylmethoxytryptamine, Figure 5 is a neurohormone derived from amino acid tryptophan.

It is involved in circadian rhythms but also acts as a potent antioxidant, protecting cell membranes against lipid peroxidation Beyer et al. It has been described to be more effective in ROS scavenging than vitamin E, GSH, vitamin C and β-carotene Watson, Coenzyme Q10 or ubiquinone 2,3-dimethoxymethylpolyisoprene parabenzoquinone, Figure 5 is an isoprenoid antioxidant present in cell membranes, essential for ETC Tafazoli, Its synthesis starts from oligomerization of isoprenoid building blocks, isopentenyl pyrophosphate and dimethylallyl pyrophosphate both arising from the mevalonate pathway and the key enzyme 3-hydroxymethyl-glutaryl-CoA reductase E.

The resulting decaprenyl diphosphate is then conjugated with a tyrosine derivative to yield the active form of the coenzyme. It is one of the few liposoluble antioxidants, ensuring lipoproteins and lipids protection from radical chain reactions, peroxidation and oxidative damage Lee et al.

In its active form quinol , coenzyme Q10 can scavenge several ROS or regenerate other oxidized antioxidants including vitamins C and E. In turn, the quinone form can be reduced back by several NAD P H-dependent enzymatic systems. Exogenous antioxidants need to be supplemented continuously through the diet since their synthetic pathways are usually present only in microbial or plant cells.

Vitamins, two of which show prominent antioxidant effects, such as vitamins C and E, belong to essential class of molecules. Vitamin C ascorbic acid exists in two redox forms: ascorbic acid AA is the reduced form, which is deprotonated at physiological pH thus, occurring in its anion form, ascorbate.

Due to its high electron-donating power, AA can undergo two-electron oxidation, yielding dehydroascorbic acid DHA. One-electron oxidation of AA is also possible, generating a semi-dehydro-ascorbyl radical Kocot et al. DHA can be regenerated to the active AA form by GSH- or Trx-dependent mechanisms.

Humans do not express the enzyme L -gulonolactone oxidase E. Thus, AA must be ingested by food or supplements , particularly tomatoes, pineapples, watermelons and all citrus fruits Banafsheh and Sirous, AA effectively quenches ROS, both directly and cooperatively regenerating oxidized vitamin E, GSH, and carotenoids.

Vitamin E is a fat-soluble vitamin, mostly found in several vegetable oils, nuts, broccoli and fish. Eight different forms have been reported α-, β-, γ-, and δ-tocopherol, and α-, β-, γ-, and δ-tocotrienol , but α-tocopherol has the highest antioxidant activity, especially in cell membranes Salehi et al.

A variously methyl-substituted chromanol ring characterizes tocopherols. A long phytyl chain gives the hydrophobicity Figure 6. Figure 6. Chemical structures of Vitamin C, Curcumin, Resveratrol, Quercetin, Vitamin E, β-carotene, Lycopene.

On the contrary, tocotrienols bear an unsaturated isoprenoid chain. α-Tocopherol is able to undergo hydrogen transfer to several ROS, including 1 O 2 , superoxide anion and peroxyl radicals. The oxidized and radical derivative of vitamin E is then reduced by the AA.

Carotenoids are a broad class of tetraterpenes, widely distributed among plants. Carotenes are also vitamin A precursors. Carotenoids protect plant chlorophyll, acting as accessory pigments during photosynthesis.

Thus, they are intensely colored red, orange, or yellow molecules. Carotenoids have been suggested to be chemopreventive agents in cancer Marti et al. Their biological activities also include ROS scavenging Hernández-Almanza et al.

β-Carotene comprises one of the most diffused carotenes, being the primary pro-vitamin A precursor, and it is found mainly in carrots, pumpkins, mangoes and apricots. Lycopene is another well-known acyclic carotene, not being a precursor of vitamin A, and is found primarily in tomatoes and other red fruits, but not in strawberries and cherries.

Indeed, carotenoids are strong ROS scavengers, operating a very particular physical and chemical 1 O 2 quenching Banafsheh and Sirous, In the physical mechanism, the carotenoid electron-rich structure absorbs 1 O 2 excess energy, reaching an excited state.

The conjugated double bond structure in carotenoids is responsible for this ability. The excited state then decays to the ground state, losing the surplus energy as heat.

During this cycle, the structure of this molecule stays unchanged. Polyphenols are a large class of plant secondary metabolites, whose synthesis is usually possible only in these organisms Sanjust et al. The key enzyme [phenylalanine ammonia-lyase PAL , EC 4.

PAL catalyzes the non-oxidative deamination of phenylalanine to trans -cinnamic acid, which is the fundamental building block for polyphenol synthesis in the phenylpropanoid pathway Ertani et al. Several biological functions have been ascribed to polyphenols, including anti-inflammatory, antioxidant, antimicrobial and antimelanogenesis effects Zucca et al.

For instance, one of the most studied polyphenols has been curcumin, gaining a lot of attention also for nutraceutical applications. Curcumin can also increase GSH cellular levels Banafsheh and Sirous, Epigallocatechingallate EGCG is a well-known antioxidant.

The green tea catechins include catechin, epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate Barbieri et al.

Flavonoids, in addition to its strong antioxidant properties, quench ROS formation inhibiting several enzymes and chelating metals involved in radical chain reactions Banafsheh and Sirous, Furthermore, flavonoids can also affect free metal ion concentrations. Indeed, flavonoids have the well-known capacity to chelate several metal ions such as iron and copper , blocking free radical generation Kumar and Pandey, For instance, quercetin is one of the most diffused flavonols present in broccoli, apples, grapes, onions and soybeans, with both iron-chelating and iron-stabilizing abilities Kumar and Pandey, On the other hand, catechol and galloyl-derivatives are generally well-known metal chelators Jomova and Valko, So, they can all exert their antioxidant activity by blocking Fenton-like reactions.

Organosulfur compounds have also been suggested as potent antioxidants. The most studied are probably some sulfur-containing metabolites present in garlic mainly S -allyl-mercapto cysteine, S -allyl cysteine, and diallyl sulfide, diallyl trisulfide Kimura et al.

These organosulfur are also responsible for typical garlic flavor. Their antioxidant actions include scavenging ROS and inhibiting lipids peroxidation Borek, ; Miltonprabu et al. Several minerals, in small amounts, are also essential for some enzymatic antioxidant activities.

They are therefore sometimes regarded as antioxidants themselves. For instance, selenium is a necessary component of GPX Battin and Brumaghim, , while copper, zinc, and manganese are fundamental for SOD activity.

The balance between ROS production and purification maintains homeostasis of the body, but is most often directed to the formation of free radicals and involvement in the pathophysiology of chronic diseases. The use of antioxidant supplements containing multivitamins and minerals has always grown in popularity among consumers.

But some recent studies have not shown any beneficial effect of antioxidant therapy. Oxidative stress has a dual character: it is both harmful and beneficial to the body, because some ROS are signaling molecules on cellular signaling pathways.

Lowering the level of oxidative stress through antioxidant supplements is therefore not beneficial in such cases Ye et al. Antioxidants are also prone to oxidation since oxidation and reduction reactions do not happen in isolation. AA, a potent antioxidant, mediates several physiological responses.

This reaction is responsible for oxidative stress-produced DNA damage. However, the role of AA as anti- or pro-oxidant depends on the dose used, as observed in the case of ischemia-induced oxidative stress Seo and Lee, With increased oxygen tension, carotenoids tend to lose their antioxidant potential.

Otherwise, α-tocopherol, a powerful antioxidant, becomes pro-oxidant at high concentrations Cillard and Cillard, Interestingly, when it reacts with a free radical, it becomes a radical in itself. If there is not enough AA for its regeneration, it will remain in that highly reactive state Lü et al.

Flavonoids can also act as pro-oxidants depending on the concentrations used Prochazkova et al. Nevertheless, the extent to which these phytochemicals are capable of acting as anti- or pro-oxidants in vivo is still poorly understood, and this topic undoubtedly requires further research.

The hypothesis that antioxidants could protect against cancer because they can neutralize reactive oxygen species ROS that can damage DNA has long been issued. In laboratory and animal studies, the presence of elevated levels of exogenous antioxidants has been shown to prevent the types of free radicals that have been associated with the development of cancer.

A few randomized studies evaluating the role of antioxidant supplements for cancer prevention were conducted in collaboration with the National Cancer Institute Goodman et al. No data were obtained to justify that they are effective in primary cancer prevention.

An analysis in the United States concluded that there is no clear scientific evidence for the benefits of vitamin and mineral supplements in cancer prevention.

It is important to point out that there have been cases where people who have resorted to these types of supplements have encountered an unfavorable evolution of the disease. Preclinical studies also report that antioxidants have contributed to the expansion of tumor processes in animal models.

A well-known case is that of vitamin A, for which the administration of high doses in supplements has been associated with an increased risk of cancer.

Vitamin A can be obtained preformed from animal sources or plant products, derived from β-carotene. β-Carotene is an orange pigment found in fruits and vegetables carrots, sweet potatoes, mangoes, apricots , and in the body it is converted to vitamin A. A normal intake has a beneficial effect against the risk of cancer.

However, studies have shown a correlation between the administration of β-carotene supplements and the risk of bladder cancer, as well as the risk of lung cancer in smokers Lin et al. In another study, the administration of α-tocopherol and β-carotene for lung cancer did not change the incidence of lung cancer.

However, α-tocopherol supplements have been shown to be effective in prostate cancer whose incidence is reduced Goodman et al. A trial evaluated the effectiveness of long-term supplementation with vitamin E and vitamin C in the risk of developing cancer. One of the findings of the study was that these types of supplements do not reduce the risk of prostate cancer or the overall risk of cancer in men of middle age or older.

No significant results were obtained regarding the risk of colorectal or lung cancer Gaziano et al. Vitamin E and C supplements showed poor results in many studies.

There was a reduction in cardiovascular mortality, but no significant effect was observed on overall mortality. The authors concluded that vitamin E supplementation for the prevention of cardiovascular disease among healthy women is not justified.

Moreover, cancer mortality is not significantly influenced by vitamin E supplementation Lee et al. The Selenium and Vitamin E Cancer Prevention Trial SELECT which included over 35, men over the age of 50, showed that selenium and vitamin E supplements do not prevent prostate cancer.

This article summarizes the evidence from a large number of meta-analyzes covering the pathophysiological impact of antioxidants on the most common chronic diseases. The main criticism of the review is that the data were extracted from meta-analyzes and not from individual studies, but this can be considered an advantage because meta-analyzes provide the highest degree of evidence.

In the case of antioxidants, studies show that more does not necessarily mean better. Consuming superfoods does not compensate for other unhealthy eating habits or an unbalanced lifestyle. Free radicals, as well as antioxidants, can have beneficial effects on the body.

Therefore, we are talking about a balance and not a negative role attributed to free radicals and a positive one to antioxidants. Degradation of nucleic acids, proteins, lipids or other cellular components are among the effects that an excessive concentration of free radicals can generate.

Risk factors leading to free radicals include air pollution, ionizing radiation, prolonged exercise, infections, excessive consumption of polyunsaturated fatty acids Poprac et al.

On the other hand, antioxidants are considered to be the solution to these problems — substances that neutralize free radicals. In some situations, some substances act as antioxidants, in other situations they become prooxidants, depending on the chemical composition of the environment in which they are.

There are many types of antioxidants, and the role in the body and the mechanisms by which they act are different. One misconception is that one antioxidant can be replaced with another, having the same effect.

In fact, each has its own unique biological properties Chen X. There is also a significant difference between taking antioxidants from food and administering an isolated substance as a supplement. Many substances that demonstrate beneficial effects in the laboratory do not work when introduced into the human body.

Many antioxidants do not have good bioavailability. The concentration of antioxidants such as polyphenols is sometimes so low in the blood that no significant effect is observed Fernández-García et al.

Fruits and vegetables contain bioactive substances that in many cases do not work as antioxidants if we consider them outside of the body. But they work as antioxidants when they are in the body, because they activate their own antioxidant mechanisms.

These bioactive substances are the secret behind vegetable consumption Kurutas, Antioxidant supplements may have different health benefits. On the one hand, it is possible that other substances present in food are responsible for the positive effects on health, not necessarily a certain type of antioxidant, but the synergistic effect of several substances.

On the other hand, the chemical structure of antioxidants in food is often different from that identified in supplements. An example is vitamin E. There are eight variants of vitamin E in the foods we eat, while the supplements used in most studies contain only one form Firuzi et al.

Studies also frequently include healthy people, for whom oxidative stress on the body is not significant to determine a risk of disease. Antioxidants can benefit certain categories of patients in whom there is a real, documented imbalance, but it may not bring anything extra for a person who gets a sufficient amount of nutrients from their diet.

Observational studies analyze the trends, or habits of certain large population groups. In many, all the risk factors that could influence the course of the study can be controlled, and demonstrating a cause-effect relationship is difficult. We also cannot rely on small studies, carried out over a short period of time and using very concentrated substances extracted from different plant or animal products, to say that we have a superfood.

Nutrition is a complex science, and at the moment we can only rely on the evidence accumulated so far. A food rich in antioxidants will not compensate for an unhealthy lifestyle.

Oxidative stress can be reduced by approaching a balanced lifestyle. Nutrition plays a critical role, and the best treatment against oxidative stress is antioxidants.

Oxidative stress plays an important role in the pathogenesis of potentially severe conditions. In the long term, increasing the level of prooxidant factors can cause structural defects in mitochondrial DNA and alterations in enzymatic functionality or cellular structures, with the appearance of functional, structural abnormalities or aberrations in gene expression.

To control these effects, the epithelium of the lung is protected by a lining of fluid containing an armamentarium of antioxidants. When the equilibrium between the antioxidants and oxidants is compromised then it leads to oxidative stress.

In response to this stress, an inflammatory response is directed which results in the release of different cytokines and pro-inflammatory chemokines. This leads to the invasion of leukocytes and monocytes into the inflammatory environment.

Continuous inhalation of injurious agents directs the initiation of prolonged oxidative stress in the lungs, which results in chronic inflammation characterized by a pronounced release of reactive nitrogen and oxygen species.

This condition is related to significant DNA damage and genomic instability, leading to neoplastic progression and initiation Valavanidis et al. Different evidence has shown that oxidative stress plays a potent role in the development of hepatic carcinogenesis by disrupting genetic material, the normal functioning of the cell, and by interfering with various pathways of cell signaling Jain et al.

The application of antioxidant agents can limit oxidative stress-directed damages in vitro. But no drug is found to be effective under in vivo conditions with a smaller number of side effects.

To find a more effective method for the cure and treatment of HCC, research for a better understanding of the mechanism involved in the development of cancer, OS-induced damage, and the effects of antioxidants is urgently required Wang et al. The liver is the main organ that is targeted by reactive species.

Primary cells, i. The peroxisomes, microsomes, and mitochondria in parenchymal cells lead the production of ROS by regulating the PPARα, which is involved in the expression of genes related to fatty acid oxidation.

Moreover, endothelial cells, hepatic stellate cells, and kupffer cells are more sensitive towards oxidative stress-associated molecules. Different types of cytokines such as TNF-α can be released in Kupffer cells in response to oxidative stress, which might trigger the process of apoptosis and inflammation Li S et al.

Colorectal cancer is the most common cancer globally, with the greatest incidence in Western nations. This cancer arises from the epithelial cells that line the bowel.

The epithelial cells reported to have a great metabolic rate and divide rapidly which has been considered to be a potent factor responsible for the oxidation of DNA. Studies on rat colonocytes reported that the lower crypt cells are very much more sensitive towards hydrogen peroxide-induced damage than the differentiated cells located at the crypt surface Perše, Since proliferating cells in the colon are present in the lower part of the crypt, this may determine that these cells are supposed to be the main targeted cells in case of colon carcinogenesis Progenitors or stem cells are very sensitive towards the redox environment.

The differentiation and self-renewal of these cells are based majorly on the redox environment of the gut mucosa. Proliferating cells are also found to be sensitive to DNA damage as DNA is available in the form of a sgle strands in the S-phase of the cell cycle and further serves as a template in daughter cells.

The damage of DNA in a single strand can lead to multiple mutations in the DNA of daughter cells, which could not get repaired Oberreuther-Moschner et al. DNA damage causes genomic instability, replication error, induction of signal transduction pathways, induction of transcription and cell cycle arrest, all of which are related to colon carcinoma.

However, the latest investigation has reported that the production of ROS may play a vital role in all the phases of carcinogenesis, i. Breast tumor with increased proliferative capacity produces a great level of ROS during the chronic cycles of angiogenesis, reperfusion, and ischemia.

Tumor cells can direct oxidative damage in surrounding healthy tissues. Enhanced levels of circulating malondialdehyde has been observed in the advanced stages of breast cancer as compared to early stages, which shows differences in the stage of oxidative stress.

Patients with breast cancer have been reported to have a greater level of malondialdehyde, a marker of oxidative stress and peroxidation product, than the control patients Coughlin, A breast tumor is a highly complex structure composed of old stromal and neoplastic cells.

Carcinoma-associated fibroblasts CAFs has been usually reported in the cancer stroma, where they enhance vascularity and tumor growth. Under the influence of oxidative stress, fibroblast gets activated to become myofibroblast.

These cells are greatly contractile and mobile and more often express mesenchymal markers. The activation of CAF is irreversible, which makes it difficult to be removed by nemesis.

They also generate hydrogen peroxide, which directs the production of different sets of tumorigenic alterations and activated fibroblasts in the case of epithelial cells.

Under oxidative stress, the tumor stroma produces a wide range of nutrients that support cancer cell survival and growth Jezierska-Drutel et al. Prostate cancer is very common among males in Western nations.

This chronic disease is very difficult to diagnose and has very limited treatment options. In vivo and in vitro studies determine oxidative stress as the main factor responsible for the occurrence of chronic prostatitis, prostatic cancer, and benign prostatic hyperplasia.

Thus, the cascade of oxidative stress is the potential target for the cure of prostate-related disorders Roumeguére et al. It includes a broad range of vital functions such as storage of material absorbed from the digestive tract, hormone catabolism, synthesis of different compounds like clotting factors, globulin, and albumin and detoxification reactions.

In alcoholic individuals, the main organ responsible for the removal of excessive alcohol is the liver and hence alcoholics are more prone to liver damage.

Alcohol gets metabolized in the liver and during its metabolism, it generates free radicals. Metabolism of ethanol results in oxidative stress in hepatocytes through the generation of ROS.

During metabolism, the molecules of alcohol break down into smaller molecules, which after further reactions leads to the production of ROS in the liver organ Ceni et al.

Alcohol promotes the production of ROS in various ways: 1 stimulating cytochrome Ps activity, 2 altering certain metal concentrations, 3 decreasing the antioxidants level, 4 directing the conversion of xanthine dehydrogenase XDO into xanthine oxidase XO. These radicals raise peroxidation of lipids which leads to liver disorders such us: 1 Ischemic reperfusion injury IRI : ROS generated by activated liver cells act as a vital mediator in liver ischemic-reperfusion injury Zhang W et al.

FIGURE 3. Highlights the impact of ROS in chronic diseases: liver, renal and kidney. The kidney is greatly vulnerable to alterations induced by ROS because of polyunsaturated fatty acids in the lipids of the kidney Ander et al.

The renal sources of ROS are leucocytes, fibroblasts, glomerular cells, interstitial cells, vascular cells, and activated macrophages. Oxidative stress played a potent role in various renal diseases such as tubule-interstitial fibrosis, ischemia-reperfusion injury, progressive and acute renal failure, and glomerulosclerosis Ratliff et al.

Oxygen radical results in the following changes: 1 These free radicals result in hypertrophy of tubular cells, 2 Oxygen radical reacts with nitric oxide which is an endothelial vasodilator and inhibits its function. Generally, renal patients required regular dialysis and this process undergoes the removal of small antioxidant molecules from the blood.

This decreases the protection against reactive species and causes peroxidation of several biomolecules such as lipids. This raised the level of oxidative stress that can further lead to renal complications Liakopoulos et al. The lung organ exists in an oxygen-rich environment. Their large blood supply and greater surface area make this organ more susceptible to damage caused by oxidative stress.

On another side, an insufficient antioxidant defence mechanism in inflammatory cells, macrophages and lung epithelial cells can also result in high-level production of endogenous ROS in the lung tissues Park et al.

Mitochondria are majorly included in ROS-dependent pathways. Mitochondrial dysfunction also plays an important role in non-energetics pathogenesis and bioenergetics metabolism in different cases of lung disease.

The genome of mitochondria acts as a guard to govern the cytotoxic response of pulmonary cells to oxidant stress Schumacker et al. Mitochondria are included in ROS-initiated lung diseases such as lung cancer, chronic airway disease, asbestos, and lung fibrosis.

The mitochondrial genome is more sensitive than the nuclear genome. Damage to mitochondrial DNA results in loss of mitochondrial membrane potential, impairment in the electron transport chain, and drives the immune and inflammatory responses Liu and Chen, , Figure 3.

Neurodegenerative diseases are a heterogenous group of disorders that are characterized by the extensive loss of neurons.

In the case of cerebral ischemia CI , oxidative stress takes part in neuroinflammatory reactions. In postischemia brains, oxidative stress directs the activation of astrocytes and microglia which brings striking elevation in the inflammatory mediators such as matrix metalloproteases, chemokines, and cytokines and results in the loss of endothelial cell integrity in the brain by upregulating the neutrophil infiltration and cell adhesion molecules.

Kim et al. The innate mechanism of PD involves inflammatory responses and a spectrum of oxidative stress that results in neurodegeneration. Overexpression of cyclooxygenase-2 COX2 is also responsible for dopaminergic neuronal loss via oxidative stress-mediated inflammation.

Enhanced OS may direct mitochondrial dysfunction, impairment in the DNA repair system, and cellular damage, all of these processes have been regarded as the key factor responsible in the acceleration of the aging process and the initiation of other neurological diseases Kim et al.

ROS work as a secondary messenger within the heart as they are indulged in various physiological processes including contraction-excitation, proliferation, and differentiation. However, when the generation of ROS exceeds the level of antioxidant molecules in the heart, oxidative stress arises, which results from heart failure, cell death, hypertrophy, ischemia-reperfusion injury, and cardiac dysfunction.

Endogenous ROSs in the heart are produced by uncoupled nitric oxide synthase, monoamine oxidases, cytochrome P, NADPH oxidase, and xanthine oxidoreductase. Rheumatoid arthritis RA is a condition which gives rise to oxidative stress. A 5-fold increase in the concentration of mitochondrial ROS in monocyte and whole blood of RA patients is reported as compared with a healthy individual which suggests that OS has a pathogenic effect in RA.

Ponist et al. Free radicals or reactive species are indirectly associated with joint damage, as they play the role of secondary messenger in the immune and inflammatory response in RA. The exposure of T-cells to raised OS become refractory to different stimuli including those for death and growth and may preserve the abnormal immune response.

On the other hand, free radicals directly degrade the joint cartilage by targeting its proteoglycan and restricting its synthesis. Oxidative products of lipid peroxidation, oxidative damage of hyaluronic acid, and oxidation of low-density carbonyl and lipoproteins increment have been observed in RA patients.

Raised levels of synovial fluid and 4-HNE have also been determined in the serum of RA patients Ponist et al.

A cataract is a partial or complete opacification on or in the human lens or in the capsule, which degrades vision. It is the main cause of reversible blindness in the globe today.

It is determined that oxidation is an initial stage in the sequence of steps that lead to cataracts. Researchers have proposed a variety of factors which are related to the onset of cataractogenesis: enhanced permeability of the lens membrane, a decreased function of chaperone related to alpha crystalline, augmented non-enzymatic glycosylation, enhanced lipid peroxidation, and low capacity of antioxidant defence mechanism.

These results have shown that the OS plays a major role in the pathogenesis of cataracts, which can be ameliorated and prevented by antioxidant molecules Kaur et al. Mizanur Rahaman et al. The initial study on the antioxidant is majorly focused on their application in preventing unsaturated fats from getting rancid.

However, the identification of vitamin E, C, and A in the living organism has led to an understandiof ng the function of antioxidants.

They are usually divided into non-enzymatic and enzymatic. Among them, there are different types of compounds with different places amodesode of action and varied final effects Flieger et al. They act as metal-chelatisynergists synergist, enzyme inhibitor, singscavengersn scavengedecomposerse decomposerdonorsctron donors, hydrogen donor, and radical scavenger Sharifi-Rad et al.

Both non-enzymatic and enzymatic antioxidants exist in extracellular and intracellular environment to detoxify the ROS. Two main principal mechanisms of action of that described for antioxidants are: The first mechanism is chain breaking in which primary antioxidants donated an electron to the free radicals whereas the second mechanism directs the removal of reactive species initiators secondary antioxidants by quenching the catalyst that initiate the chain of reaction.

So, antioxidants extra t efonct in biological ssystemswith the help of various mechanisms such as gene expression regulation, co-antioxidants, metal ion chelation, and electron donation Lobo et al.

Antioxidants are the agent that when available in low concentration in comparison to the oxidizable substrate remarkably reduces or delays the oxidation of the substrate. The endogenous system is further categorized into non-enzymatic and enzymatic groups.

The main function of antioxidants is to detoxify the reactive species in the body Kurutas, Figure 4 shows the sites of action that are targeted by different antioxidants. Every cell releases an antioxidant enzyme which protects the cells during the metabolism of oxygen, and further breaks down the harmful free radicals into balanced molecules like water Lobo et al.

Living organisms have evolved a system for the scavenging of free radicals and reactive species. In another step, the hydrogen peroxide generated is eliminated by GPx and catalase system. Various isoenzymes of SOD are indulged in the scavenging activity of free radicals. Another extracellular Cu-Zn-dependent isoenzyme is also reported.

Two different mechanisms have been reported for the SOD action that restricts the transformation 1 It majorly acts at the cell membrane level and eliminate or prevent the generation of radical that can result from the peroxidation of lipid and leads to the chain of extra-nuclear and nuclear events, ultimately cause transformation.

This concept explains the model of a membrane that mediates chromosomal aberration, 2 It has been reported that oxygen radicals could be generated in a growth medium and act as a promoter of transformation that will be removed by SOD Kowald et al. Catalase is present exclusively in peroxisomes.

The purified form of catalase contains four subunits of protein, each of which has a heme Fe III-protoporphyrin group attached to its active site. Catalase is reported to play a dual role Nandi et al. A catalytic role in the decomposition of H 2 O 2.

A peroxidic role to oxidize a range of H donors AH 2. DNA cleavage by X-ray and mitomycin C induced malignant transformation which was found to be suppressed by the catalase enzyme. According to some studies, factors such as brain-derived neurotrophic factor BNDF and stress are responsible for the antioxidant activity of several endogenous antioxidants Lobo et al.

The mice with BNDF deficiency under the stress circumstances showed increased activity of catalase enzyme in comparison to the stressed wild type. This indicates that the capacity to scavenge free radicals was reduced and this determines that the normal wild type has better tolerance capability than the BNDF heterogeneous mice Hacioglu et al.

The system of glutathione includes glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and glutathione. This system is reported in microorganisms, plants and animals.

Glutathione peroxidase is an enzyme that contains 4 units of selenium as cofactors which catalyzes the breakdown of organic hydroperoxides and hydrogen peroxides. About four different isoenzymes of glutathione peroxidase are reported in animals.

Glutathione peroxidase 1 is the efficient scavenger of hydrogen peroxide while glutathione peroxidase 4 is found to be more effective with lipid hydroperoxides.

The glutathione S-transferase shows greater activity with lipid peroxides. These enzymes are present at high concentrations in the liver and also help in the metabolism of detoxification Lobo et al.

Glutathione is a non-protein thiol that coordinates the processes of antioxidant defense in the body. Alterations in the status of glutathione have been reported to cause several complications.

Administration of thiol compounds such as methionine, cysteine, and glutathione are known to protect against oxidative stress in animals and humans. The reduced form of thiols has been utilized for the recycling of other antioxidants such as vitamin C and vitamin E Noctor et al.

Protection against OS is largely depending upon the reductive power of NADPH, whose level is evaluated with the help of glucosephosphate dehydrogenase G6PD. Animal cells contain few enzymes that can generate NADPH, and among them, G6PD is the most important one Peters and Van Noorden, G6PD catalysis is the rate-limiting step of the pentose phosphate pathway PPP , which provide nucleotide precursors for DNA replication, as well as reductive power to NADPH for the detoxification of ROS and de novo synthesis of lipid Stanton, The relation of PPP and G6PD in the detoxification of ROS is determined by the fact that mice deficient in G6PD have higher levels of oxidative damage in the brain.

Animal cells also respond against oxidative stress by enhancing their PPP-directed NADPH production. The overexpression of G6PD in Drosophila melanogaster protects against oxidative stress and can also expand their lifespan Nóbrega-Pereira et al.

Exogenous antioxidants like vitamins E, C, and A played a supporting role. They scavenge the free radicals and reactive species by donating an electron and maintaining a chemical balance. These dietary agents get saturated easily, only once as they donate the electron Table 1. TABLE 1. Classification of major antioxidants and their roles.

Vitamin E alpha-tocopherol is considered to be an important antioxidant that involves in the chain-breaking process in the case of humans. Vitamin E is present within the cell membrane to interrupt the peroxidation of lipid and also play a major role in the modulation of cell signaling pathways that are dependent on reactive oxygen intermediates ROI.

Vitamin E also plays a potent role in decreasing the cases of cancer. It functions by donating the hydrogen atom to fatty peroxyl radicals and disrupting the lipid peroxidation process. It also has the potential to make a reaction with two peroxyl radicals as shown below:.

The vitamin E synthesized in Equation assumes to have a resonance-stabilized conformation which allows this vitamin to react with other peroxyl radicals to form a stable adduct, LOO-α-tocopherol. Alpha-tocopherol restricts the generation of new free radical whereas gamma-tocopherol neutralizes or trap the existing reactive species.

OS has been associated with various possible diseases but rather vitamin E helps to delay or prevent the chronic ailments associated with free reactive molecules Traber and Stevens, Uric acid, cysteine, glutathione, and vitamin C ascorbic acid work as a hydrophilic scavenger of oxygen radicals Lobo et al.

Natural ascorbate restricts the carcinogenic process of various nitroso compounds, fed to animals by converting them to an inactive form. This vitamin C can be utilized to detoxify the different organic compounds in vivo by a simple reduction process Combet et al.

Ascorbic acid is a potent scavenger and reducing agent of reactive species in the biological system. It is included in the first line of ddefenceof antioxidants, protecting the proteins and lipid membrane from damage Pehlivan, Due to its water-soluble nature, vitamin C can work both outside and inside the cells and can neutralize the free reactive species to avoid any damage.

This vitamin works as an excellent source of electrons for the reactive species that are finding out an electron to acquire their stability. They can donate electrons to those free radicals and scavenge their reactivity Padayatty and Levine, Cysteine is the physiological precursor of glutathione GSH and has been known widely for its protective function against mutagenesis and radiation.

ß -Carotene is also found to be useful in decreasing the incidence of cancer. Two major functions of ß -carotene are the ability to neutralize and trap certain organic free radicals and to deactivate the oxygen radicals present in exciting form, produced as a byproduct of metabolic reactions Fiedor and Burda, The consistent and strongest conformation regarding the protective effect of large consumption of carotene-rich food comes from studies of the esophagus and lung cancer Patel et al.

ß -Carotene act as an antioxidant under low oxygen tension and can also act as a prooxidant under more oxidizing and high concentration level in the case of smokers Tapiero et al. A sole molecule of ß -carotene is determined to eliminate around 1, of singlet oxygen with the help of a physical mechanism which involves the transfer of energy before it gets oxidized and loses its antioxidant activity Tan et al.

The rate of ß -carotene oxidation is dependent upon the partial pressure of oxygen. The carbon-centred radicals get resonance stabilized when the oxygen pressure is lowered. The ß -carotene activity towards peroxyl radicals and the stability of other carbon-centred radicals are the two main features that provide the carotene molecule with its antioxidant properties Fiedor and Burda, Selenium is a natural element which has gained focus due to its potential to decrease the process of carcinogenesis.

The antioxidant activity of selenium concerning vitamin C was studied broadly Tan et al. Deficiency of selenium results in the consequent cellular and tissue damage raised peroxidation of lipids and leads to the formation of free radicals. Damage caused to unsaturated fatty acids in the subcellular membrane by peroxidation reaction can be reduced by Se and vitamin E Mourente et al.

The metabolisms of Se and vitamin E are interrelated and Se plays a major role in vitamin E storage. Phenolic compounds are a heterogenous group of phytocompounds that are broadly spread in the plant kingdom Chaudhary et al. Flavonoid belongs to a class of naturally occurring polyphenolic compounds and they provide different colors to leaves, fruit, and flower Chaudhary et al.

Flavonoids are further divided into the following classes: anthocyanidins, flavones, flavonols, flavanones, and flavonols. Among the classes, variations are based on the arrangement and number of hydroxyl groups, and glycosylation or alkylation of these groups.

The broad varieties of flavonoids and the greatest difference in their content make it difficult to determine the daily intake estimate of flavonoids Panche et al. Phenolics and flavonoids act as an antioxidant through several pathways The most potent one is likely to be by scavenging the free radicals in which polyphenols carried out the breakdown of several free radical chain reactions Kaurinovic and Vastag, For a molecule to act as an antioxidant, it must fulfil the two criteria.

i at low concentrations, it can prevent the oxidation of the substrate. ii the radical generated on the polyphenols must be stable enough so that it can prevent itself from acting as a chain-propagating radical Dangles, This stabilization is usually through intramolecular hydrogen bonding and delocalization or by reaction with other lipid radicals and further oxidation.

A large number of investigations have been done on the structure-antioxidant activity relationship of flavonoids Table 2. Some of the common ones are flavanol, flavonoid, and quercetin which are abundant in onion, broccoli, and apple; catechin, another flavanol present in different tea and fruits; naringenin, the major flavanone in grapefruit; glycitein, genistein, and daidzein are the major isoflavanones in soybean; and cyanogen glycosides are abundant in blackberry, raspberry, and black currant.

Curcumins target free radicals through various mechanisms. Additionally, curcumin is a lipophilic molecule, which makes it useful in the scavenging of peroxyl radicals. Therefore, like vitamin E, curcumin is also utilized as a chain-breaking natural agent.

Tannin is the common name for phenolic molecules that are used for tanning leather and the precipitation of gelatin from solution. They are further categorized into the condensed form of proanthocyanidins, in which the main structural unit is the phenolic flavanol nucleus and hexahydroxydiphenoyl and galloyl ester and their derivatives, ellagitannins and gallotannins Clifford and Scalbert, The two main groups of phenolic acids are hydroxycinnamic acid and hydroxybenzoic acid, both of which are obtained from cinnamic acid and benzoid molecule, respectively Kumar and Goel, These phenolic acids contain benzoic acid derivatives such as cinnamic acid derivatives ferulic, caffeic and coumaric acid and gallic acid.

Caffeic acid is majorly found in vegetables and fruits, most commonly esterified with quinic acid as in chlorogenic acid, the main phenolic in coffee. Another common phenolic acid is ferulic acid which is esterified with hemicellulose and present in cereals Dai and Mumper, Caffeic acid is produced by different plant species and is found to be available in various food products such as tea, wine, and coffee and other medicines such as propolis.

Phenolic acid and its derivatives have anticarcinogenic, anti-inflammatory, and antioxidant activities. In vivo and in vitro investigations have determined the anticarcinogenic property of this agent in the case of hepatocarcinoma, which is considered to be a highly aggressive form of cancer, responsible for the large rate of mortality across the globe.

The anticancer activity of this compound is related to its pro-oxidant and antioxidant capacity due to its complex structure including double bond in the carbonic chain, the position and number of OH group and free phenolic hydroxyl in the catechol group, respectively Kiokias et al.

The pharmacokinetic investigation determined that this compound is being hydrolyzed by the microbial colonies and metabolized in the mucosa of the intestine through phase II enzymes, submitted to methylation and conjugation process, forming methylated, glucuronic, and sulphated conjugates by the action of o-methyltransferase, UDP-glucosyltransferases, and sulfotransferases, respectively Monteiro Espindola et al.

The transmembrane flux of this compound in intestinal cells occurs via the active transport carried out by the carriers of monocarboxylic acid. It can act by suppressing the expression of MMP-9 and MMP-2, blocking STATs, reducing the angiogenesis of tumor cells, inducing the oxidation of DNA of tumor cells, and preventing the generation of ROS Monteiro Espindola et al.

It can induce apoptosis, autophagy, and cell cycle arrest via activating the ROS generation and caspase pathway. Additionally, they can restrict metastasis and invasion by reducing the activity and expression of matrix metalloproteinase Kahkeshani et al. The antioxidant activity of ferulic acid is very complex.

It is majorly based on the restriction of RNS and ROS formation and neutralization of free radicals. This compound also acts as a hydrogen donor; donating atoms directly to free radicals. This acid is found to be important for the protection of lipidic acids in the cell membrane from the unwanted autoxidation process.

As a secondary compound, ferulic acid and its derivatives can bind with copper and iron and avoid the generation of toxic hydroxyl radicals, which direct cellular damage Zduńska et al. This acid is extracted from Rosmarinus and Salvia species and reported with various antioxidant and functional properties.

It is most commonly used in the pharmaceuticals and cosmetic sector. This acid is most commonly found in cereals, vegetables and fruits. It acts as a potent antioxidant and scavenges free radicals and reactive species.

p-coumaric acid is a phenolic acid and is a hydroxyl derivative of cinnamic acid. It reduces the prefigure oxidation of low-density lipoprotein and decreases the risk of stomach cancer Kiliç and Yeşiloğlu, Stilbenes comprise two phenyl moieties which are connected by the methylene bridge of two carbon atoms.

Majorly these compounds act as an antifungal phytoalexin, the compound which is synthesized in response to injury. One of the widely known stilbenes is resveratrol, found majorly in grapes.

Products of red wine and grapes contain a significant amount of resveratrol, respectively Rocha-González et al. Lignans are the phenolic compounds and have 2,3-dibenzylbutane structures that is resulted from the dimerization of two cinnamic acid residues; lignans such as secoisolariciresinol are considered phytoestrogen.

The increasing interest in the beneficial effect of phenolic compounds has resulted in the development of such diets that are rich in vegetables and fruits and provide protection against cancer and cardiovascular diseases.

The linseed act as a source which provides secoisolariciresinol up to 3. Erythroxylum cuneatum , a tropical flowering plant of the Erythroxylaceae family utilized in Thailand and Malaysia as traditional medicine.

The alkaloid extract of E. cuneatum leaf possesses both anti-inflammatory and antioxidative activity suggesting its role in the development of anti-inflammatory and antioxidant drugs Li S et al.

Two isoquinoline alkaloids kareemine 2 and iraqiine 1 , along with N-methylouregidione 7 , atherospermidine 6 , O-methylmoschatoline 5 , kinabaline 4 , and muniranine 3 were isolated from the dichloromethane extract of Alphonsea cylindrica bark. Compounds 4, 3, and 1 possess higher DPPH scavenging activity Obaid Aldulaimi et al.

The antioxidant activity of alkaloid boldine and Peumus boldus extract was reported against Fe II -citrate-induced damage in rat liver mitochondria in vitro Klimaczewski et al. Stephania rotunda Lour. The antioxidant activity of fangchinoline and cepharanthine was reported from Stephania rotunda by in vitro assays Gülçin et al.

The results determined an effective radical scavenging and antioxidant activity of fangchinoline and cepharanthine. Five new alkaloids 1—5 along with two new phenanthrene and three aporphine alkaloids, in total 10 6—15 compounds were isolated from the roots of Stephania tetandra.

Based on electronic circular dichroism, single crystal X-ray, and spectroscopic analysis, compound 13, and 7—10 exhibited great antioxidant activities Wang R et al. Terpenes play an important role in the metabolic processes of a broad range of microorganisms, plants, and animals in which they are formed Naturally, terpenoids can be utilized for different purposes including as key agents in metabolic processes, signaling, and defense Baccouri and Rajhi, These terpenes have had applications in medicine, cosmetics, and perfumery for thousands of years and are still procured from different plants for the above-mentioned uses.

The antioxidant activities of terpenes may explain their capacity to adjust the neural signal transmission, immunological effects, and inflammation. They protect against oxidative stress situations including ageing, diabetes, neurodegenerative, cardiovascular disease, cancer, liver, and renal mechanisms Baccouri and Rajhi, Bourgou et al.

essential oils and also their ability in restricting the production of nitric oxides. The chemical characterization and antioxidant activity of essential oils isolated from Euphorbia heterophylla L. Elshamy et al. Sesquiterpenes-rich essential oil isolated from the above parts of Pulicaria somalensis showed great antioxidant activity and allelopathic effect against weeds Assaeed et al.

In a study to determine the antitumor effects of terpenoids, it was found that paclitaxel, geraniol, and perillyl alcohol are the terpenoids with better anticancer activities Yang et al.

The anti-inflammatory activity of paeoniflorin and its derivatives, 4-O-methylbenzoyl paeoniflorin, 4-O-methyl paeoniflorin, and other monoterpenes was reported Bi et al. The results reported that most of these monoterpenes can inhibit the production of tumor necrosis factor-alpha TNF-α , interleukins-6 IL-6 , and inflammatory factor nitric oxide NO induced by lipopolysaccharides LPs.

Other free radicals such as ROOH, and organic hydroperoxide are generated by the reaction of radicals with the cellular components such as nucleobases and lipids.

The RO, ROO. peroxyl, and alkoxy radicals are oxygen centered organic types of radicals. Lipids form take part in the peroxidation reaction of lipids. They are generated in the presence of oxygen by abstraction of hydrogen and addition of radicals to double bonds. Hypochlorous acid or HOCl are generated from hydrogen peroxide in the presence of myeloperoxidase.

They are highly reactive and readily oxidized protein constituents such as methionine, amino groups, and thiol groups. Peroxynitrite radical is generated in a reaction of superoxide with nitric oxide. The protonation reaction results in the formation of peroxynitrous acid which undergo hemolytic cleavage to form nitrogen dioxide and hydroxyl radicals Lobo et al.

Therefore, various methods have been applied to decrease the damage caused by oxidative stress. Endogenous antioxidant enzymes which are generated inside the cells work as a protective mechanism against reactive free species.

Heme oxygenase, reductase, thioredoxin, GST, GR, GPx, CAT and SOD are the most vital antioxidant enzymes. Thus, there is a conversion of toxic species to the harmless product. Peroxides generated during the process of metabolism, get eliminated by GPx and GST. So, GRd functions by raising the concentration of GSH, which is required for the maintenance of oxide-redox conditions in a living organism.

The GPx is available throughout the cells whereas CAT is restricted to the peroxisome. The brain is very sensitive towards the damage caused by free radicals so; it contains 7 times more concentration of GPx than the CAT.

The greatest level of CAT is found in erythrocytes, kidneys, and the liver, where it decomposes most of the hydrogen peroxide Aziz et al. The utilization and consumption of oxygen in physiological processes result in the production of ROS. The production of energy in mitochondria is dependent upon the metabolism of oxygen since oxygen gets reduced to water.

Other antioxidant agents such as green tea extract are also capable of reducing the damage resulting from superoxide radicals. These radicals are found to be toxic to macromolecules such as proteins, lipids, and DNA. The application of various polyphenol and polyene from different vegetables and fruits protect against the damaging effect of hydroxyl radicals Lipinski, Large numbers of metals are responsible for inducing carcinogenicity and toxicity in the animal body.

An excessive amount of iron in the body leads to cancer, vascular diseases and other neurological complications. Copper at higher concentrations is known to result in metastasis. The complexes of cobalt ion led to the production of ROS which cause heart complications.

Research showed that Se can chelate copper ions efficiently and prevent the damage caused to DNA by hydroxyl radicals. The component of red wine binds to high-density lipoprotein HDL and low-density lipoprotein LDL and protect lipoproteins from metal-independent and meta-dependent lipid and protein oxidation Ivanov et al.

According to some studies, melanoidin possessed better scavenging and metal-ion chelating activity which were due to its molecular weight Wu et al. It has been determined that the major source of free radicals in diverse pathological and physiological circumstances is related to the enzyme number.

The enzymes that lead the generation of superoxide include NADPH-dependent oxidase, cyclooxygenase, lipoxygenase, and xanthine oxidase.

The production of hydrogen peroxide is catalyzed by the superoxide dismutase enzyme. Various enzymes of peroxisomes such as D-aspartate oxidase, xanthine oxidase, urate oxidase, D-amino acid oxidase and acyl CoA oxidase direct the production of different ROS. Many natural agents have revealed their potential to restrict the enzymes that direct the generation of free radicals as well as in the development of novel therapeutics agents against oxidative stress-induced diseases Phaniendra et al.

Plant alkaloids such as berberine carried out the inhibition of NADPH oxidase activity via reducing the mRNA expression of gp91phox in macrophages.

Lipid peroxidation is damaging due to the production of products which leads to the spread of free radical reactions. The potent function of lipids in the cellular system emphasizes the need to understand the consequences and mechanism of lipid peroxidation in the human body.

Polyunsaturated fatty acids PUFAs are utilized as the substrate for the peroxidation of lipids due to the presence of active bis-allylic methylene groups. The hydrogen-carbon bonds on these methylene units have very low bond-dissociation energy, making the hydrogen atom to be abstracted easily in the radical reactions Davies and Guo, It has been determined that the a -tocopherol is the most suitable antioxidant and protect the membrane from oxidation by reacting with the various lipid radicals generated in the peroxidation chain reaction of lipid.

It carried out the removal of free radical intermediates and prevents the continuation of the propagation reaction Mostafa Abd El-Aal, The natural agent, rosmarinic acid spontaneously penetrates the cell membrane to inhibit the peroxidation of lipids in situ as reported by Fadel et al.

Oxidative stress is the major reason behind the majority of DNA damage in the case of human beings. Various factors are responsible for the production of free radicals and ROS. Antioxidant agents include external antioxidants and internal antioxidants that can be consumed through a diet to fulfil the natural need of the human body.

These agents can scavenge free radicals and prevent further damage Jamshidi et al.

Often Antiioxidant Antioxidant and oxidative stress a marketing buzzword, learn about the role of antioxidants beyond Antioxiidant Antioxidant and oxidative stress, and strese of the research Antioxivant health and Quercetin and immune system prevention. Jump to: — What are antioxidants? Another constant threat comes from chemicals called free radicals. In very high levels, they are capable of damaging cells and genetic material. The body generates free radicals as the inevitable byproducts of turning food into energy. Free radicals are also formed after exercising or exposure to cigarette smoke, air pollution, and sunlight. Free radicals come in many shapes, sizes, and chemical configurations. Oxidative stress plays an essential role Green tea extract and skin health the pathogenesis of chronic diseases such as nad diseases, Antioxidant and oxidative stress, neurodegenerative diseases, anv cancer. Long oxdiative exposure to increased levels of pro-oxidant factors can Green tea extract and skin health structural defects at Antioxidatn mitochondrial DNA oxidativw, as MRI for kidney disorders as functional alteration of Bacterial defense systems enzymes and cellular structures leading to aberrations Antiodidant gene Antoxidant. The modern Ajtioxidant associated with oxidatjve food, exposure to oxidativve wide range of chemicals and lack of exercise plays an important role in oxidative stress induction. However, the use of medicinal plants with antioxidant properties has been exploited for their ability to treat or prevent several human pathologies in which oxidative stress seems to be one of the causes. In this review we discuss the diseases in which oxidative stress is one of the triggers and the plant-derived antioxidant compounds with their mechanisms of antioxidant defenses that can help in the prevention of these diseases. Finally, both the beneficial and detrimental effects of antioxidant molecules that are used to reduce oxidative stress in several human conditions are discussed. Many natural biological processes in our bodies, such as breathing, digesting food, metabolize alcohol and drugs, and turning fats into energy produce harmful compounds called free radicals.