Authors: PRIYANKA CHANDRA, RINKI & PARUL SUNDHA
CONCEPT OF FREE RADICALS
By definition a free radical is any atom (e.g. oxygen, nitrogen) with at least one unpaired electron in the outermost shell and is capable of independent existence. A free radical is easily formed when a covalent bond between two entities is broken and one electron remains with each newly formed atom. Free radicals are highly reactive due to the presence of unpaired electron(s). Generally two types of free radicals; reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in human physiology. Any free radical involving oxygen can be referred to as reactive oxygen species (ROS) and free radical involving nitrogen is referred as reactive nitrogen species (RNS). Free radicals present a paradox in their biological function: on one hand, they prevent diseases by assisting the immune system, mediating cell signaling and playing an essential role in apoptosis. On the other hand, they can damage important macromolecules in cells and may have a role in aging, carcinogenesis and cardiovascular diseases.
NEED OF ANTIOXIDANTS
Since in the late 19th and early 20th century, chemists have studied antioxidants as a loosely defined group of compounds characterized by their ability to be oxidized in place of other compounds present. Their uses range from food storage to the vulcanization of rubber, but it was only later that biologists realized the importance of antioxidants in health with the 1960s publications of vitamins and flavonoids, followed by later research in the 1970s on ascorbic acid (vitamin C), cancer, and the common cold.
An antioxidant is a molecule capable of slowing or preventing the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons from a substance to an oxidizing agent. Oxidation reaction can produce free radicals, which start chain reactions that damage cells. Antioxidants terminate these chain reactions by removing or stabilizing free radicals, and inhibit other oxidation reactions by being oxidized themselves.
Antioxidant systems exist in cells to protect against ROS. Antioxidants in aqueous compartments, for example the cytosol and the extracellular fluids, consist of low molecular weight antioxidants such as glutathione, ascorbate (vitamin C) and antioxidant enzymes such as superoxide dismutases (SOD), catalases and peroxidases.
TYPES OF ANTIOXIDANTS
For protecting against oxidative damage, aerobic cells are equipped with a variety of non enzymatic antioxidants and antioxidative enzymes with different functions, by which cellular redox-status homeostasis is ensured through the scavenging of various preformed free radicals. Non-enzymatic antioxidants are represented by ascorbic acid (vitamin C), α-tocopherol (vitamin E), glutathione (GSH), vitamin A, carotenoids, flavonoids, and other antioxidants. The cellular radical-scavenging systems include the enzymes such as superoxide dismutase (SOD), which scavenge the superoxide ion by speeding up its dismutation, catalase (CAT), a haeme enzyme, which removes hydrogen peroxide and glutathione peroxidase (GP X), a selenium-containing enzyme, which scavenges other peroxides as well as hydrogen peroxide. These enzymes form a first line of defense from oxidative stress. If the free radical production becomes more than the capacity of enzymatic system to cope up with, then the second line of defense (vitamins) may come to rescue. Vitamin A and C quench free radicals by oxidizing and inactivating them (Table 1).
ANTIOXIDANTS FROM NATURAL SOURCES
Antioxidants are used in dietary supplements in the hope of maintaining health and preventing diseases such as cancer and coronary heart disease. As synthetic antioxidants exhibit carcinogenic and toxic nature, researchers focused to search natural antioxidants which led to the identification of vitamins A, C, and E as antioxidants.
Epidemiological studies have shown that higher intake of fresh vegetables, fruits, tea and wines, which are proved as good source of natural antioxidants and are associated with reduced risk of heart disease. This is the reason for the strong interest in natural antioxidants and their role in human health and nutrition. A number of dietary antioxidants include various phytochemicals such as vitamin C, vitamin E, α- tocopherol, β-carotene and phenolic compounds. The antioxidant activity of these phytochemicals range from slight to extremely high.
The natural antioxidants from plants and mushrooms have been known to play important roles in promotive health and the treatment of various diseases. Several plants (medicinal plants, spices, vegetables, fruits) and mushrooms have been studied as sources of potentially safe natural antioxidants. Various compounds have been isolated and many of them are phenolic which are effective hydrogen donors and able to inactivate lipid peroxidation or prevent decomposition of hydro peroxides into free radicals as well as chelate metal ions which make them good antioxidants.
Table 1 Mechanism of action of various antioxidants against different diseases
| Compound | Pathology | Mechanism of action |
| Catalase (CAT) | Cancer, diabetic retinopathy | Destroys hydrogen peroxide in high concentration by catalysing its two-electron dismutation into oxygen and water |
| Glutathione peroxidase (GPx) | Neurodegenerative diseases | Catalyse the reduction of hydroperoxides at the expense of GSH. In this process, hydrogen peroxide is reduced to water whereas organic hydroperoxides are reduced to alcohols |
| Superoxide dismutase (SOD) | Neurodegenerative diseases | Catalyse the one-electron dismutation of superoxide into hydrogen peroxide and oxygen |
| Alkaloids | Cancer, Neurodegenerative diseases, chronic inflammation | Shown a variety of biological activities such as inhibition of topoisomerase I and II; cytotoxicity against different tumor cell lines |
| Catechins | Neurodegenerative diseases | Enhance activity of SOD and catalase |
| Carotenoids | Cancer, diabetic retinopathy, chronic inflammation | Mainly act as physical quenchers of reactive oxygen |
| α-tocopherol | Cancer, neurodegenerative diseases, chronic inflammation | Scavenges lipid peroxyl radicals (LOO) through hydrogen atom transfer |
| (+)- epigallocatechin 3- gallate | Neurodegenerative Conditions | Decreases the expression of proapototic genes (bax, bad, caspase-1 and -6, cyclin dependent kinase inhibitor) thus maintaining the integrity of the mitochondrial membrane |
| (-)-epigallocatechin 3- gallate | Cancer, diabetic retinopathy, chronic inflammation | Suppression of angiogenesis |
| Ferulic acid | Diabetes | Decrease lipid peroxidation and enhances the level of glutathione and antioxidant enzymes |
| Glutathione | Cancer | Glutathione in the nucleus maintains the redox state of critical protein sulphydryls that are necessary for DNA repair and expression |
| Proanthocyanidin | Cardiovascular disorders | Inhibitory effects on proapoptotic and cardioregulatory genes |
| Phenolics | Cancer, diabetic retinopathy, chronic inflammation | Inhibit the oxidation of lipids, fats, and proteins (RH) by donation of a phenolic hydrogen atom to the free radical |
| Quercetin, Kaempferol, Genistein, Resveratrol | Colon cancer | Suppresses COX-2 expression by inhibiting tyrosine kinases important for induction of COX-2 gene expression |
| Tannins | Cardiovascular disorders | Tannins are known to enhance synthesis of nitric oxide and relax vascular segments precontracted with nor epinephrine |
| Flavonoids | Cancer, Cardiovascular disorders | Affect cancer cells and inhibit tumor invasion, strong topoisomerase inhibitors and induce DNA mutations in the MLL gene, which are common findings in neonatal acute leukemia |
References:
1. Muller, J. K.S, Madsen, H. L., Aaltonen, T. and Skibsted, L. H. (1999). Dittany (Origanum dictamnus) as a source of water-extractable antioxidants. Food Chemistry 64: 215-219.
2. Leaver, M.J. and George, S.G. (1998). A piscine glutathione S-transferase which efficiently conjugates the end-products of lipid peroxidation. Marine Environmental Research 46: 71-74.
About Author / Additional Info:
Priyanka Chandra and Parul Sundha are scientist at ICAR-Central Soil Salinity Research Institute, Karnal and Rinki is Scientist at ICAR-Indian Institute of Wheat and Barley Research, Karnal .