Substances that inhibit oxidative changes in molecules. Many oxidative changes are destructive, and this applies as much to the human body as to non-biological chemistry.  But oxidation is also a need to get energy. Without energy, there is no living. This implies we do need controlled oxidation and when it becomes a threat to wellbeing it should be constrained. This is the role of antioxidants: constrain the negative effects of oxidation.

Anti oxidants and the way free radicals work


The oxygen molecule (O2) is relatively stable.  Many oxygen-containing compounds on the other hand, such as peroxides and superoxide, are highly reactive free radicals, collectively called “reactive oxygen species” or ROS.  ROS are often byproducts of cellular energy production.  Many, like superoxide, are produced by the body using enzymes for goal-related purposes.  Free radicals containing nitrogen are referred to as “reactive nitrogen species” or RNS.  RNS result from the reaction of nitric oxide and superoxide to produce peroxynitrite, and related compounds.  Both ROS and RNS are highly reactive and can damage proteins, lipids, and DNA.  RNS-induced damage is sometimes referred to as “nitrosative stress, to distinguish it from “oxidative stress.” 

Due to their destructive potential, superoxide and RNS are produced by the body as a defense to foreign pathogens.  Superoxide production is controlled by a regulated network of enzymes.   Sulfur-containing radicals are referred to as “RSS” (reactive Sulphur species). They result from the reaction of thiols with ROS.  Both RNS and RSS result from reactions involving ROS. 

Reactive oxygen species (ROS) some returning questions answered. 

(1) Are all free-radicals are positively charged?

positively charged free radicals in biological systems are not common. The fact is that most biological free radicals are negative or neutral. They follow the octet rule.

(2) Are all antioxidants negatively charged?

There are a few, but most of them are neutral. Generally, antioxidants have conjugated pi systems, which allow electron delocalization and different resonance structures.  This allows the antioxidant to donate an electron to a radical without becoming overly reactive itself.


How positive ions work

Prooxidant refers to any endobiotic or xenobiotic that induces oxidative stress either by the generation of ROS or by inhibiting antioxidant systems. It can include all reactive, free radical containing molecules in cells or tissues. Prooxidants may be classified into several categories.

Some antioxidant flavonoids have acted as prooxidant when a transition metal is available. The antioxidant activities and the copper-initiated prooxidant activities of these flavonoids depend on their structures. The OH substitution is necessary for the antioxidant activity of a flavonoid. Flavone and flavanone, which have no OH substitutions and which provide the basic chemical structures for the flavonoids, show neither antioxidant activities nor copper-initiated prooxidant activities. The copper initiated prooxidant activity of a flavonoid also depends on the number of free OH substitutions on its structure. The more the OH substitutions, the stronger the prooxidant activity. O-Methylation and probably also other O-modifications of the flavonoid OH substitutions inactivate both the antioxidant and the prooxidant activities of the flavonoids.

Sample: The antioxidant activity of quercetin (a yellow crystalline pigment C15H10O7 occurring usually in the form of glycosides in various plants ) has been found to be better than its monoglucosides in a test system wherein lipid peroxidation was facilitated by aqueous oxygen radicals. Luteolin (a yellow coloring substance, C15H10O6, obtained from the weed Reseda luteola: used in dyeing silk and, formerly, in medicine. ) has proved to be a significantly stronger antioxidant than its two glycosides.

Flavonoids generally occur in foods as O-glycosides with sugars bound at the C3 position. Methylation or glycosidic modification of the OH substitutions leads to the inactivation of transition metal-initiated prooxidant activity of a flavonoid.

Vegetables as green as they can come

The protection provided by fruits and vegetables against diseases, including cancer and cardiovascular diseases, has been attributed to the various antioxidants, including flavonoids, contained in these foods. Flavonoids, such as quercetin and kaempferol, induce nuclear DNA damage and lipid peroxidation in the presence of transition metals.


To counteract the harmful effects taking place in the cell, the physical system has evolved itself with some strategies like prevention of damage, repair mechanism to alleviate the oxidative damages, protection mechanism against damage, and antioxidant defense mechanisms.

Based on the oxidative stress-related free radical theory (Denham Harman), antioxidants are the first line of action against the effects of stress. Endogenous antioxidant defenses include a network of antioxidant enzymic and non enzymic molecules that are distributed within the cytoplasm and various cell organelles. In eukaryotic organisms, several ubiquitous primary antioxidant enzymes, such as SOD, catalase, and several peroxidases catalyze a complex cascade of reactions to convert ROS to more stable molecules, such as water and O2. Besides the primary antioxidant enzymes, many secondary enzymes act in close association with small molecular-weight antioxidants to form redox cycles that provide necessary cofactors for primary antioxidant enzyme functions.

Small molecular-weight non-enzymic antioxidants (e.g., GSH, NADPH, thioredoxin, vitamins E and C, and trace metals, such as selenium) function as direct scavengers of ROS. These enzymatic and non-enzymatic antioxidant systems are necessary for sustaining life by maintaining a delicate intracellular redox balance and minimizing undesirable cellular damage caused by ROS. Endogenous and exogenous antioxidants include some high molecular weight (SOD, GPx, Catalase, albumin, transferring, metallothionein) and some low molecular weight substances (uric acid, ascorbic acid, lipoic acid, glutathione, ubiquinol, tocopherol/vitamin E, flavonoids).

Natural food-derived components have received attention in the last two decades, and several biological activities showing promising anti-inflammatory, antioxidant, and anti-apoptotic-modulatory potential have been identified. Flavonoids comprise a large heterogeneous group of benzopyran derivatives present in fruits, vegetables, and herbs. They are secondary plant metabolites and more than 4000 molecular species have been described. Flavonoids exert a positive health effect, owing to their free radical-scavenging activities. One flavonoid present in a large number of fruits and vegetables is quercetin (3,5,7,3′,4′, pentahydroxyflavone) which prevents oxidative injury and cell death by scavenging free radicals, donating hydrogen compound, quenching singlet oxygen, and preventing lipid peroxidation or chelating metal ions. Red wines have a high content of phenolic substances including catechin and resveratrol, which are responsible for the antioxidant action, anti-inflammatory, antiatherogenic property, estrogenic growth-promoting effect, and immunomodulation.

Oxidative Stress

Oxidative stress in carcinogenesis – lJames E.Klaunig & ZeminWang

The mitochondrion is the major cell organelle responsible for ROS production. It generates ATP through a series of oxidative phosphorylation processes. During this process, one- or two-electron reductions instead of four-electron reductions of O2 can occur, leading to the formation of superoxide and H2O2, and these can be converted to other ROS. Other sources of ROS may be reactions involving peroxisomal oxidases, cytochrome P-450 enzymes, NAD (P)H oxidases, or xanthine oxidase (黄嘌呤;黄质.

The central nervous system (CNS) is extremely sensitive to free radical damage because of a relatively small defensive antioxidant capacity. The ROS produced in the tissues can inflict direct damage to macromolecules, such as lipids, nucleic acids, and proteins. Oxygen-free radicals, particularly superoxide anion radical, hydroxyl radical (OH•−), and alkylperoxyl radical (•OOCR), are potent initiators of lipid peroxidation. Once lipid peroxidation is initiated, a propagation of chain reactions takes place until termination products are produced. The end products of lipid peroxidation, are such as malondialdehyde (MDA), 4-hydroxy-2-nonenol (4-HNE), and F2-isoprostanes, are accumulated in biological systems.

DNA bases are very susceptible to ROS oxidation, and the predominant detectable oxidation product of DNA bases in vivo is 8-hydroxy-2-deoxyguanosine. Oxidation of DNA bases can cause mutations and deletions in both nuclear and mitochondrial DNA. Mitochondrial DNA is prone to oxidative damage due to its proximity to a primary source of ROS and its deficient repair capacity compared with nuclear DNA. These oxidative modifications lead to functional changes in various types of proteins (enzymatic and structural), which can have a 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), is 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 an 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 dismutases 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 Body’s Natural Antioxidant Defenses

Natural Antioxidant Anthocyanins—A Hidden Therapeutic Candidate in Metabolic Disorders with Major Focus in Neurodegeneration by Rahat Ullah 1,†,Mehtab Khan 1,†,Shahid Ali Shah 1,2,Kamran Saeed 1 andMyeong Ok Kim 1,*

To detoxify ROS, the body uses a system of antioxidants, such as antioxidative enzymes, e.g. superoxide dismutase, catalase, glutathione peroxidase. This system consists of degradative yet and other enzymes such as proteases, peptidases, phospholipases, acyltransferases, endonucleases, exonucleases, polymerases, ligases, etc., to leave and replace irreversibly damaged macromolecules. Importantly, the systems are integrated, they work to continue the close interaction.

Superoxide Dismutase (SOD) catalyzes the reduction of superoxide into hydrogen peroxide and water.  In mammals, there are three isoforms that function in distinct cellular compartments.  SOD1 is found in the cytosol and mitochondrial intermembrane.  SOD2 is located in the mitochondrial matrix; and  SOD3 functions in the extracellular space.

Glutathione Peroxidase (Gpx) transforms peroxides, especially lipid hydroperoxides, into water and alcohol.  Specialized GPx forms function in distinct cellular compartments in specific tissue types.  Analysis of the selenoproteome identified five glutathione peroxidases (GPxs) in mammals: cytosolic GPx (cGPx, GPx1), phospholipid hydroperoxide GPx (PHGPX, GPx4), plasma GPx (pGPX, GPx3), gastrointestinal GPx (GI-GPx, GPx2) and, in humans, GPx6, which is restricted to the olfactory system. GPxs reduce hydroperoxides to the corresponding alcohols by means of glutathione (GSH). They have long been considered to only act as antioxidant enzymes. Increasing evidence, however, suggests that nature has not created redundant GPxs just to detoxify hydroperoxides. In conclusion, cGPx, PGPX, and GI-GPx have distinct roles, particularly in cellular defense mechanisms.

Catalase (CAT) uses iron to reduce peroxides.  Hundreds of different forms are widely distributed in animal, plant, and fungi tissues.  Some contain manganese, and some are bifunctional catalase-peroxidases.

In addition to these principal antioxidant enzymes, the secondary antioxidant enzymes, thioredoxin, glutaredoxin, and peroxiredoxin systems also aid in the control, and selective removal, of ROS.  The body is able to increase or decrease their activity in target locations, as needed, to maintain ideal redox homeostasis.  Antioxidant enzymes cannot be taken orally; it would not be advisable to do so, even if possible.