Abstract
Antioxidants neutralize free radicals produced by various environmental insults such as ultraviolet radiation, cigarette smoke and air pollutants, thereby preventing cellular damage. The role of oxidative stress and antioxidants is known in diseases like obesity, atherosclerosis, and Alzheimer’s disease. Herein we discuss the effects of oxidative stress on the skin and role of antioxidants in dermatology.
INTRODUCTION
Aging is a process of progressive decrease in the functioning and reserve capacity of all organs in the body, including the skin (intrinsic or chronological aging). This naturally occurring functional decline in the skin is often compounded and accelerated by chronic environmental insults such as ultraviolet radiation, pollutants, smoking etc., (extrinsic aging).[1]
THEORY OF AGING AND FREE RADICALS
One of the important theories for aging is the free radical theory, which was proposed by Denham Harman in the 1950s, wherein the generation of free radicals results in damage to biomolecules including DNA. This idea was later extended in the 1970s to implicate mitochondrial production of reactive oxygen species (ROS).[2,3,4] Later this theory was expanded to include other diseases such as malignancies, vitiligo, Alzheimer’s disease, atherosclerosis etc.[4,5]
Free radicals are compounds formed when oxygen molecule combines with other molecules yielding an odd number of electrons.[6] The molecules which are oxygen-centred are ROS and those which have nitrogen are reactive nitrogen species (RNS).[5,7] These free radicals with an unpaired electron seek and seize electrons from vital components such as DNA, cytoskeleton, cellular proteins and cell membranes, resulting in cellular damage [Figure 1].[8]
The important ROS are superoxide anion (O2–), peroxide, hydroxyl radical (OH), hydroxyl ion, and singlet oxygen (1O2).[9] Nitric oxide (NO) and peroxynitrite (ONOO–) are the major RNS in biological systems.[7]
Exogenous sources of ROS are air pollutants, ozone, radiation, chemicals, smoking, toxins, and pathogenic microorganisms.[6] Endogenous source of ROS includes leaks in electron transport chain found in mitochondria during oxidation of food stuffs or inflammatory cells. These produce free radicals by a process of respiratory burst during phagocytosis or enzymes, which indirectly produce free radicals.[10]
SKIN AND FREE RADICALS
In the healthy skin, practically all types of skin cells produce reactive oxygen (ROS) and reactive nitrogen (RNS) species. These free radicals are indispensable effectors in the homeostatic pathways leading to cell proliferation, differentiation, senescence, and death.[7] An elaborate network of endogenous antioxidants maintain homeostasis by neutralizing these free radicals from causing damage to cells. When this fine balance between free radicals and endogenous antioxidants is lost, it results in a phenomenon called oxidative stress. Chronic oxidative stress has been suggested as being the cause or consequence of many acute and chronic human diseases e.g. obesity, cardiovascular diseases, cancer, acute lung injury, retinal degeneration, Alzheimer’s disease, Parkinson disease and multiple sclerosis.[4,5] Oxidative stress also play a role in various dermatological disorders like aging of skin e.g., solar elastosis, deep wrinkles, coarse texture, telangiectasia and pigmentation, psoriasis, allergic contact dermatitis, atopic dermatitis, vitiligo, acne vulgaris, pemphigus vulgaris (PV), lichen planus, alopecia areata, and melanomas.[7,9,11,12]
Various pathogenic mechanisms are responsible for these lesions such as induction of transcription factors that includes Activator protein (AP-1) and Nuclear factor κB (NF-κB) which are responsible for inflammatory changes, metalloproteinase (MMP) like collagenase which causes decreased collagen production, increased collagen breakdown, and increased elastin accumulation resulting in features of aging and lastly mitogenic activated protein kinase (MAPK), which is one of the factor responsible for skin cancers.[6]
ANTIOXIDANTS
Antioxidants are those molecules which are capable of inhibiting the oxidation of other molecules.[5] Oxidation is a process where there is loss of electrons or an increase in oxidation state by a molecule, atom or ion.
As the number of molecules having antioxidant properties is increasing with each passing day, it is difficult to keep abreast with all of them. Commonly used antioxidants in dermatology are classified as endogenous and exogenous [Table 1].[6,9,13]
Naturally occurring antioxidants work in synergy with each other i.e. if an antioxidant disarms a free radical by eliminating the odd number of electrons it will no longer be able to function as an antioxidant unless it is replenished. This is done by another antioxidant and its synergy is called network antioxidation. The participating antioxidants are referred to as network antioxidants.[6,14]
DISTRIBUTION OF ANTIOXIDANTS IN SKIN
Skin is endowed with natural antioxidants as it is exposed to numerous environmental insults. Vitamin E, catalase, superoxide dismutases, glutathione peroxidases are abundantly present in the viable layer of the epidermis. The extracellular space of skin epidermis and dermis, contains large amounts of antioxidants such as ascorbic acid, uric acid, and glutathione. The outer most layer, the cornified envelope of normal human skin contains antioxidants such as glutathione, vitamin C, uric acid, α-tocopherol, squalene, and coenzyme Q10, distributed in a gradient with the highest concentration on the deepest cornified envelope layers.[7]
Summary of important antioxidants is given in Table 2.[6,9,15]
Antioxidant activity
The antioxidant activity of various antioxidants is studied using four parameters – Trolox equivalent antioxidant capacity (TEAC), oxygen radical absorbing capacity (ORAC), ferric reducing antioxidant capacity (FRAP), free radical scavenging properties by diphenyl-1-picrylhydrazyl radical (DPPH).
The antioxidant potency composite index, is based on [(sample score/best score) × 100] that is averaged for all the parameters for each beverage. It was found that pomegranate has the highest antioxidant activity. Following is the list of beverages and their potency index [Table 3].[16]
Since most antioxidants are dietary supplements, their side effects are supposed to be negligible such as presence of irritation with topical vitamin E or retinoids, and occurrence of peripheral vasodilatation or cutaneous flushing with oral niacin.[15]
Though there is a lot of interest about the role of antioxidants available for the treatment of various dermatoses, it is important to know that most of the studies have demonstrated an in vitro role of these molecules as antioxidants. There is paucity of clinical trials regarding their role to prevent aging of skin.[6,15] Also, there are certain problems in combining these molecules with creams such as sunscreens as it is found that many of these molecules are unstable and if stabilized, they tend to have lesser antioxidant capacity to neutralize the free radicals.[9] On the positive side, few recent studies have also shown that combining various antioxidants can have a synergistic action.[17]
CONCLUSION
Free radicals can damage the DNA, lipid membrane, collagen structures, and also play a role in photo aging and skin cancer. Oral and topical antioxidants have the ability to provide benefits from free radical damage, but long term studies are necessary to validate these findings.
