ANTIOXIDANTS AND FREE RADICALS

FREE RADICALS

A free radical is an atom or molecule with an unpaired electron in its outer shell, making it unstable and highly reactive. It will then try to steal an electron from a nearby molecule to stabilise itself. Once a free radical forms and succeeds in gaining another electron from a nearby molecule, its victim becomes a free radical since it is now short an electron. This unstable molecule will then try to steal an electron also. The result is referred to as a free radical cascade (1).

Free radical reactions are expected to produce progressive adverse changes that accumulate with age throughout the body—these manifest as diseases at certain ages determined by genetic and environmental factors. Cancer and atherosclerosis, two significant causes of death, are salient “free radical” diseases (2). Free radicals are derived either from normal essential metabolic processes in the human body, from other endogenous sources (i.e., mitochondria inflammation, phagocytosis, arachidonate pathways or exercise) or from external sources such as exposure to radiation (i.e., X-rays, ultraviolet), ozone, cigarette smoking, air pollutants, industrial chemicals, pesticides or certain drugs (2-4).

OXIDATIVE STRESS

A balance between free radicals and antioxidants is necessary for normal physiological function. A common form of free radicals in aerobic organisms is oxygen free radicals, known as reactive oxygen species (ROS) (i.e., superoxides, hydroxyl anions, hydrogen peroxide and singlet oxygen) (3). When ROS flood the cellular antioxidant defence system, oxidative stress occurs (5, 6).

Oxidative stress, arising from an imbalance between free radical production and antioxidant defences, is associated with damage to a wide range of molecular species, including lipids, proteins, and nucleic acids (2). The initiation, promotion, and progression of cancer and the side effects of radiation and chemotherapy have been linked to the imbalance between ROS and the antioxidant defence system. ROS have been implicated in the development and complications of diabetes mellitus. ROS have also been implicated in age-related eye disease, ageing and neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and muscular dystrophy (7-10).

Oxidative stress has been incriminated in many conditions, including heart diseases, stroke and certain cancers. It is also thought to contribute to all inflammatory diseases significantly (e.g., arthritis, lupus erythematous), acquired immunodeficiency syndrome, gastric ulcers, or smoking-related diseases (2, 7, 8).

FREE RADICAL-INDUCED DAMAGE

Free radical cascades in the body often end when a molecule that loses an electron becomes altered or can not properly function, leading to damage to the cell that contains it since the molecule often becomes defective. Free radicals can damage molecules such as DNA, proteins, carbohydrates, and lipids leading to cell and tissue damage. In the skin, over time, this damage leads to visible signs of ageing (i.e., fine lines, wrinkles, discolouration, reduced firmness, and skin cancer) (11).

AGEING AND FREE RADICALS

In the 1950s, Denham Harman introduced the free radical theory of ageing, which states that organisms age because cells accumulate free radical damage over time (12, 13). This later became known as the mitochondrial theory of ageing, which implicates mitochondria in generating ROS, stating that ROS produced in the mitochondria cause damage to lipids, proteins and most importantly, mitochondrial DNA. As a result, the free radical theory includes ageing and age-related diseases (15-16).

ANTIOXIDANTS

An antioxidant is a molecule that can donate an electron to an unstable free radical without becoming destabilised themselves, thus reducing free radicals’ capacity to cause damage (2, 18). These antioxidants mainly delay or inhibit cellular damage through their free radical scavenging property and can safely interact with free radicals to prevent damage to vital molecules. Some antioxidants are produced during normal metabolism in the body (e.g., glutathione, ubiquinol, and uric acid). Other lighter antioxidants are found in the diet and include vitamin E, vitamin C and B-carotene (2, 19-22)

Endogenous antioxidants are the body’s natural way to protect its cells from free radical damage. However, the effectiveness of the body’s endogenous antioxidant system decreases with age, making supplementation essential (e.g., from diet) (23).

PROTECTING THE SKIN FROM UV-INDUCED FREE RADICALS

Extrinsic factors, especially sun exposure, essentially influence clinical signs of ageing. As UV exposure may be responsible for 80% of visible facial ageing signs (24), there are ways to slow the skin’s ageing process. Sunscreen can protect the skin from UV-induced free radicals, but it is essential to remember that sunscreen cannot stop all the UV rays from penetrating the skin (25). Other ways to protect the skin from UV damage and free radicals include using Vitamin C and Vitamin E serums before applying sunscreen. Pairing antioxidants Vitamin C and E as topical serums with sunscreen will significantly increase the protection of your skin.

REFERENCES

1. Cheeseman KH, Slater TF. An introduction to free radicals’ chemistry. Br Med Bull 1993; 49:481–93.
2. Lobo., A. Patil., A. Phatak. & N. Chandra. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacognosy Reviews. (2010). 4(8): p118-126.
3. Ebadi M. Antioxidants and free radicals in health and disease: An introduction to reactive oxygen species, oxidative injury, neuronal cell death and therapy in neurodegenerative diseases. Arizona: Prominent Press 2001.
4. Devasagayam TPA, Tilak JC et al. Free radicals and antioxidants in human health: current status and future prospects. Journal of Association of Physicians of India 2004; 52:794–804
5. 4 Rock CL, Jacob RA, Bowen PE. Update on biological characteristics of the antioxidant micronutrients-Vitamin C, Vitamin E and carotenoids. J Am Diet Assoc. 1996; 96:693–702.
6. Mc Cord JM. The evolution of free radicals and oxidative stress. Am J Med. 2000; 108:652–9.
7. Trachootham D, Alexandre J, Huang P. Nat Rev Drug Discov 2009;8:579–91.
8. Valko M, Rhodes CJ et al. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact 2006; 160:1-40.
9. Haigis MC, Yanker BA. The Aging Stress Response. Mol Cell 2010;40(2):333-44.
10. Rao AL, Bharani M, Pallavi V. Role of antioxidants and free radicals in health and disease. Adv Pharmacol Toxicol 2006; 7:29–38.
11. Young IS, Woodside JV. Antioxidants in health and disease. J Clin Pathol 2001; 54:176–86.
12. Hekimi S, Lapointe J, Wen Y. Taking a “good” look at free radicals in the ageing process. Trends in Cell Biology 2011;21(10) 569-76.
13. Harman D. Aging: a theory based on free radical and radiation chemistry. Journal of Gerontology 1956;11(3):298-300.
14. Harman D. A biologic clock: the mitochondria. Journal of the American Geriatrics Society 1972;20(4):145-47.
15. Harman D. Origin and evolution of the free radical theory of ageing: a brief personal history, 1954–2009. Biogerontology 2009. 10(6):773–81.
16. Jang YC, Remmen HV. The mitochondrial theory of ageing: Insight from transgenic and knockout mouse models. Experimental Gerontology 2009;44(4):256–60.
17. Halliwell B. How to characterise an antioxidant- An update. Biochem Soc Symp. 1995; 61:73–101.
18. Bagchi D et al. Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro”. Research Communications in Molecular Pathology and Pharmacology 1997.
19. Frie B, Stocker R, Ames BN. Antioxidant defences and lipid peroxidation in human blood plasma. Proc Natl Acad Sci. 1988; 37:569–71.
20. Shi HL, Noguchi N, Niki N. Comparative study on dynamics of antioxidative action of α-tocopheryl hydroquinone, ubiquinol and α-tocopherol, against lipid peroxidation. Free Radic Biol Med. 1999; 27:334–46.
21. Levine M, Ramsey SC, Daruwara R. Criteria and recommendation for Vitamin C intake. JAMA. 1991; 281:1415–23.
22. Poljsak B, Dahmane R. Free radicals and extrinsic skin ageing. Dermatol Res Pract 2012;29.
23. Flament, F., Bazin, R., Laquieze, S., Rubert, V., Simonpietri, E. & Piot, B. Effect of the sun on visible clinical signs of ageing in Caucasian skin. Clin Cosmet Investig Dermatol. 2013; 6: 221–232
24. Haywood, R., et al. Sunscreens inadequately protect against ultraviolet-A-induced free radicals in skin: implications for skin ageing and melanoma. J Invest Dermatol 2003;121(4):862-68.