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210 Indian Dermatology Online Journal -
April-June 2014 - Volume 5 - Issue 2
Address for
correspondence:
Dr. Varadraj V. Pai,
Department of
Dermatology, Goa
Medical College,
Goa ‑ 403 002, India.
E‑mail: docpai@
rediffmail.com
Department of
Dermatology, Goa
Medical College,
Goa, 1Department
of Dermatology,
Shri Dharmasthala
Manjunatheswara College
of Medical Sciences
and Hospital, Sattur,
Dharwad, Karnataka,
India
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.
Key words: Antioxidants, free radicals, oxidative stress
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).[2-4] 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 inammatory 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 ne 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
Antioxidants in dermatology
Varadraj V. Pai, Pankaj Shukla, Naveen Narayanshetty Kikkeri1
Drug Prole
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DOI: 10.4103/2229-5178.131127
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Pai, et al.: Antioxidant in dermatology
Indian Dermatology Online Journal -
April-June 2014 - Volume 5 - Issue 2
211
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 inammatory 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.
Reductant oxidation product + e-
As the number of molecules having antioxidant properties is
increasing with each passing day, it is difcult to keep abreast
with all of them. Commonly used antioxidants in dermatology
are classied 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 cornied 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
cornied 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 ushing with oral
niacin.[15]
Figure 1: Free radical formation and antioxidant quenching the free
radical
Table 1: General classification of antioxidants[6,9,13]
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Pai, et al.: Antioxidant in dermatology
212 Indian Dermatology Online Journal -
April-June 2014 - Volume 5 - Issue 2
Table 2: Summary of important antioxidants[6,9,15]
Antioxidant Properties Functions as an antioxidant Dietary source Clinical benefits
studied
Vitamin C 1. Cofactor for critical enzymes in
collagen synthesis
2. Recycling photoxidized
α‑tocopherol, thereby
regenerating vitamin E.
1. Increases collagen synthesis
2. Reduces MMP (collagenase)
expression
3. Inhibits activation of the
transcription factor NFκB
4. Inhibits tyrosinase
5. Decreases sunburn cells by
40%to 60%.
Citrus fruits, black
currants, leafy green
vegetables, and red
pepper
Photodermatoses
Post laser‑erythema
Melasma
Stretch marks
Antiinflammatory
Vitamin E Four pair of sterio isomers of
which α‑tocopherol has the
highest activity
Protects the cell membranes from
oxidative stress.
Vegetable oil, seeds,
nuts, meats
Photoaging
Antiinflammatory
Anticarcinogenic
Wound healing
Vitamin A Two forms
Retinoids
Carotenoids (b carotene and
Lycopene)
Carotenoids scavenge 1O2 and
quench lipid peroxidation.
Retinoids bind to the nuclear
receptors, retinoic acid receptors,
thereby inhibitingAP‑1 and MMP‑1
expression.
Found in red fruits and
vegetables like carrot,
sweet potatoes, pink
grape fruit, tomatoes.
Antiageing
Anticarcinogenic
Coenzyme
Q10 (ubiquinone)
Synthetic analog
is Idebenone
Fat soluble compound present
in all cells as a part of energy
transfer chain
Scavenge ROS Fish, shell fish Antiageing
Anticarcinogenic
Green tea extract High level of polyphenols
like gallocathechin‑gallate,
epicatechin‑3‑gallate,
epigallocatechin, and
epigallocatechin‑3‑gallate (EGCG).
EGCG is the most active
ingredient
Scavenges ROS
Stabilises glutathione peroxidase,
glutathione, catalase
Inhibits AP‑1and MAPK expression
Isolated form from
camellia sinensis (tea)
plant
Antiinflammatory
Anticarcinogenic
Photoprotective
Silymarin Naturally occurring polyphenolic
flavonoids.
It has 3 flavonoids, silybin,
silydianin and
silychristin. Silybin has the highest
biologic potency
Scavenges ROS
Prevents lipoprotein
oxidation.
Milk thistle plant
Silybum marianum
Antiinflammatory
Anti carcinogenic
Coffee arabica
propriety
name‑Coffee
berry
Contains polyphenols like
cholorogenic acid, pro
anthocyanidins, Quinic acid,
Ferulic acid, caffeic acid
Suppresses UVB
radiation‑induced IL‑10 and MAPK
expression
Coffee beans and fruit of
the plant
Antiinflammatory
Anticarcinogenic
Resveratrol Polyphenolic phytoalexin
compound
Inhibits UV‑B activation of NFκB
and MAPK pathway
Skin and seeds of grapes,
red wine, berries
Antiinflammatory
Anticarcinogenic
Polypodium
leucotomos
Contains polyphenols like
dihidrobenzoic acid, Ferulic acid,
caffeic acid,
vanillic acid, caffeic acid
Scavenges ROS Extract from the fern plant
Polypodium leucotomos
Photoprotective
Anticarcinogenic
Grape seed
extract (vitis
vinifera)
Rich in polyphenol like
proanthocyanidins
Inhibits UVB induced lipid
peroxidation, protein oxidation
and DNA damage
Extract from grape seed Antiageing
Antiinflammatory
Pomegranate
(punica
granatum)
Native fruit of Indian
subcontinent.
Contains two polyphenolic
compounds: anthocyanins and
tannins
Potent antioxidant
Inhibits UV‑B activation of NF κB
and MAPK pathway
Extract from peel, juice
and seed of the fruit
Antiageing
Photoprotective
Anticarcinogenic
contd
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Pai, et al.: Antioxidant in dermatology
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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]
Table 2: Contd
Antioxidant Properties Functions as an antioxidant Dietary source Clinical benefits
studied
Alpha lipoic acid It is an octanoic acid, an essential
cofactor in mitochondrial
dehydrogenases.
Metal chelation,
Scavenge ROS
Regenerate endogenous
antioxidants
Repairs oxidative damage
Endogenously produced,
also found in red meat
and Brewer’s yeast
Antiageing
Post laser erythema
Curcumin
(Curcuma Longa,
turmeric root,
haldi)
Consists of water soluble
component turmerin
and lipid soluble curcumin
Scavenge ROS
Downregulate IL‑1 and TNF α
Inhibits activation of NF‑κB and
AP‑1 pathway
Tuber of tropical turmeric
plant
Antiinflammatory
Anticarcinogenic
Wound healing
Selenium Essential trace element for
GSH peroxidase activity,
cofactor for vitamin E
regeneration.
Inhibits UV induced photodamage
Scavenge ROS
Walnut, shellfish, fish Photoprotective
Antiinflammatory
Anticarcinogenic
Acts on P. ovale
Pycnogenol (Pine
bark extract from
pinus pinaster)
Rich in polyphenol like
proanthocyanidins
Inhibits UVB induced lipid
peroxidation, protein oxidation
and DNA damage
Also found in grape seed,
cranberry, black currant
Antiageing
Antiinflammatory
L carnosine/
carcinine
Dipeptide of aminoacid B alanine
and histidine
Inhibit UV induced lipid
peroxidation
Fish and meat Antiaging
Soy isoflavones Contain isoflavones like
genistein and diadzein
Scavenge ROS Soya beans, ginko biloba Antiinflammatory
Anticarcinogenic
ROS: Reactive oxygen species, UVB: Ultraviolet B, DNA: Deoxyribose nucleic acid, GSH: Glutathione, UV: Ultraviolet, MAPK: Mitogenic activated protein kinase,
EGCG: Epigallocatechin‑3‑gallate
Table 3: Beverages and antioxidant composite index
Beverage Antioxidant composite
index
Pomegranate juice 95.8
Red wine 68.3
Grape juice 61.7
Blueberry juice 50.9
Black cherry juice 46.5
Cranberry juice 38.0
Green tea 24.2
Orange juice 19.1
Apple juice 14.6
Black tea 12.2
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 benets
from free radical damage, but long term studies are necessary
to validate these ndings.
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Cite this article as: Pai VV, Shukla P, Kikkeri NN. Antioxidants in
dermatology. Indian Dermatol Online J 2014;5:210-4.
Source of Support: Nil, Conict of Interest: None declared.
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