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Abstract and Figures

It is estimated that total sun exposure occurs non-intentionally in three quarters of our lifetimes. Our skin is exposed to majority of UV radiation during outdoor activities, e.g. walking, practicing sports, running, hiking, etc. and not when we are intentionally exposed to the sun on the beach. We rarely use sunscreens during those activities, or at least not as much and as regular as we should and are commonly prone to acute and chronic sun damage of the skin. The only protection of our skin is endogenous (synthesis of melanin and enzymatic antioxidants) and exogenous (antioxidants, which we consume from the food, like vitamins A, C, E, etc.). UV-induced photoaging of the skin becomes clinically evident with age, when endogenous antioxidative mechanisms and repair processes are not effective any more and actinic damage to the skin prevails. At this point it would be reasonable to ingest additional antioxidants and/or to apply them on the skin in topical preparations. We review endogenous and exogenous skin protection with antioxidants.
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Correspondence: Aleksandar Godic, MD, PhD, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia. Tel: 386-51-415-678. E-mail: aleksandar.
godic@gmail.com
(Rece ived 2 September 2012 ; accepted 3 December 2012 )
Introduction
More than 50.000 papers appear in Medline when a
keyword oxidative stress is typed, but not all are
related to the skin. Skin aging is a consequence of
two overlapping mechanisms, intrinsic and extrinsic
(UV-exposure, smoking) (1,2). It seems that oxida-
tive damage is the major cause and single most
important contributor of skin aging. Not only that
the free radical production increases with age but the
ability of human skin cells to repair DNA damage
steadily reduces with years and the antioxidative
defense becomes less effective (Figure 1).
The skin contains a pool of protective antioxi-
dants. It includes enzymatic antioxidants such as
glutathione peroxidase, superoxide dismutase and
catalase, and nonenzymatic low-molecular-weight
antioxidants such as vitamin E isoforms, vitamin C,
glutathione (GSH), uric acid, and ubiquinol (3).
Other potent antioxidants, which are in the skin, are
ascorbate, uric acid, carotenoids and sulphydrils.
Water-soluble antioxidants in plasma are glucose,
pyruvate, uric acid, ascorbic acid, bilirubin and
glutathione, and lipid-soluble are alpha-tocopherol,
ubiquinol-10, lycopene, ß -carotene, lutein, zeaxan-
thin and alpha-carotene (4). In general, surface of
the skin, the epidermis, contains higher concentra-
tions of antioxidants than the dermis (5). Alpha-
tocopherol is the most prominent antioxidant in the
lipophilic compartments while vitamin C and GSH
have the highest abundance in the cytosol. Hydrophilic
non-enzymatic antioxidants, including L- ascorbic
acid, GSH and uric acid are predominant antioxi-
dants in the human skin compared on an equivalent
molar basis (6). Their overall dermal and epidermal
concentration is more than 10- to 100-fold greater
than those found for vitamin E or ubi quinol. Kera-
tinocytes and skin fi broblasts contain milimolar levels
of GSH, α -tocopherol, ascorbate, and DNA repair
enzymes. The stratum corneum (SC) was found to
contain both hydrophilic and lipophilic antioxidants.
Vitamins C and E (both α γ and α -tocopherol) as well
as GSH and uric acid were found to be present in
the SC (7,8). Surprisingly, they were not distributed
evenly, but in gradient fashion, with low concentra-
tions in the outer layers, which increase toward the
deeper layers of the SC.
Journal of Cosmetic and Laser Therapy, 2013; Early Online: 1–7
ISSN 1476- 4172 print/ISS N 1476-4180 onl ine © 2013 In forma UK, Ltd.
DOI : 10. 3109 /1476 4172. 2012 .7583 80
REVIEWS OF TREATMENT STUDIES
Skin and antioxidants
BORUT POLJSAK
1 , RAJA DAHMANE
1
&
ALEKSANDAR GODIC
2
1 University of Ljubljana, Faculty of Health Studies, Zdravstvena pot 5, 1000 Ljubljana,
Slovenia, and
2 University of Ljubljana, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia
Abstract
It is estimated that total sun exposure occurs non-intentionally in three quarters of our lifetimes. Our skin is exposed to
majority of UV radiation during outdoor activities, e.g. walking, practicing sports, running, hiking, etc. and not when we
are intentionally exposed to the sun on the beach. We rarely use sunscreens during those activities, or at least not as much
and as regular as we should and are commonly prone to acute and chronic sun damage of the skin. The only protection
of our skin is endogenous (synthesis of melanin and enzymatic antioxidants) and exogenous (antioxidants, which we con-
sume from the food, like vitamins A, C, E, etc.). UV-induced photoaging of the skin becomes clinically evident with age,
when endogenous antioxidative mechanisms and repair processes are not effective any more and actinic damage to the skin
prevails. At this point it would be reasonable to ingest additional antioxidants and/or to apply them on the skin in topical
preparations. We review endogenous and exogenous skin protection with antioxidants.
Key Words: aging , antioxidants , photoaging , skin
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2 B. Poljsak et al.
Exogenous antioxidants compounds
derived from the diet
Most important preventive mechanisms against ROS-
induced damage are antioxidative enzymes, non-en-
zymatic compounds, and repair processes, but they
are less effective with aging. It would be rational at
this point to ingest additional antioxidants or to apply
them on the skin in topical preparations. The identi-
cation of free radical reactions as promoters of the
aging process implies that interventions, which limit
their production or inhibit their interactions, reduce
the disease pathogenesis and consequently rate of
aging. Dietary antioxidants play a major role in main-
taining the homeostasis of the oxidative balance. Vita-
min C (ascorbic acid), vitamin E (tocopherol),
beta-carotene and other micronutrients such as caro-
tenoids, polyphenols and selenium have been evalu-
ated as antioxidant constituents in the human diet. It
is important to obtain many different water and lipid
soluble antioxidants by intake of different kinds of
fruits and vegetables since all antioxidants work in
synergy. Thiols, which are associated with membrane
proteins, may also be important antioxidants. Tocoph-
erols and tocotrienols (vitamin E) and ascorbic acid
(vitamin C) as well as the carotenoids exhibit their
antioxidative properties through reacting with free
radicals, notably peroxyl radicals, and with singlet
molecular oxygen (1O2). RRR-alpha-tocopherol is
the major peroxyl radical scavenger in biological lipid
phases such as membranes or low-density lipopro-
teins (LDL). L-Ascorbate is present in aqueous com-
partments (e.g. cytosol, plasma, and other body
uids) and can reduce the tocopheroxyl radical; it is
also important cofactor in hydroxylations. Carote-
noids, notably beta-carotene and lycopene as well as
oxycarotenoids (e.g. zeaxanthin and lutein), exert
antioxidative functions in lipid phases by free-radical
or 1O2 quenching (9).
Many studies on usage of different antioxidants
or combinations of them with phytochemicals were
performed in order to fi nd evidence against ROS-
induced skin damage (10).
Recommended daily intake
The Dietary Reference Intake (DRI) is a system of
nutrition recommendations from the Institute
of Medicine (IOM) of the U.S. National Academy of
Sciences. The DRI system is used by both the United
States and Canada and is intended for the general
public and health professionals. The Reference Daily
Intake or Recommended Daily Intake (RDI) is the
daily intake level of a nutrient that is considered to
be suffi cient to meet the requirements of 97 98% of
healthy individuals in every demographic in the
United States (where it was developed, but has since
been adopted in other countries). The DRI values
are not currently used in nutrition labeling, where
the older Reference Daily Intakes (RDAs) are still
used. The reference values, collectively called the
Dietary Reference Intakes (DRIs), include the Rec-
ommended Dietary Allowance (RDA), the Adequate
Intake (AI), the Tolerable Upper Intake Level (UL),
and the Estimated Average Requirement (EAR). A
requirement is defi ned as the lowest continuing
intake level of a nutrient that, for a specifi ed indica-
tor of adequacy, will maintain a defi ned level of
nutriture in an individual (11) (Table I).
Tolerable upper intake levels (UL) were devel-
oped to caution against excessive intake of nutrients
(like vitamin A) that can be harmful in large amounts.
The exaggerated intake of antioxidant(s) could cause
antioxidative stress (12) and alter the complex sys-
tem of endogenous antioxidative defense of cells or
alter the necrosis or apoptosis pathways. UL is the
highest level of consumption that is considered safe
according to current data. It is recommended that
intake of certain nutrients should be from food
source only to prevent adverse effects.
Topical application and safety risk assessment
of vitamins A, C, and E
Vitamins A, C and E are most frequently used anti-
oxidants in skin-care products and authors of the
paper decided to present the summary of their risk
Consequence: Cause:
Premature skin aging
Clinical signs of the aging skin
Increased oxidative stress
Inflammatory reactions
Immunosupression
Depleated cutaneous antioxidants
Oxidised proteins, DNA and lipids
Premalignant and malignant skin lesion
Intrinsic free radical formation
Oxidative
stress Skin aging
Extrinsic free radical formation
Figure 1. Causes and consequences of skin aging.
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Skin and antioxidants 3
Table I. Recommended daily intakes.
Nutrient Recommended daily intake*** (**)
Intakes recommended
by the FAO/WHO
Tolerable upper intake
level (UL)
Concentration in
foods (mg/100 g)
Over dosage (mg or μg/d),
side-effects and warnings Signifi cant sources
Vitamin A 600 μg
5 000 International Unit (IU)
Recommended Dietary Allowance*
Male: 1000 (μg)a
Female: 800 (μg)a
600 μg 3 000 μgExtremely high doses
( 9 000 mg) can cause dry,
scaly skin, fatigue, nausea,
loss of appetite, bone and
joint pains and headaches.
Vitamin A is not
recommended for pregnant
women. Excess vitamin A
may cause birth defects.
However, an adequate
supply of vitamin A is still
required because of its
essential role in embryonic
development.
turkey, carrot juice,
pumpkin
Vitamin C
(ascorbic acid)
75 mg
Recommended Dietary Allowance*
Male: 60 mg
Female: 60 mg
30 mg 2 000 mg 10–170 No impacts of over dose have
been proven so far.
Cooking may destroy vitamin
C in fruits and vegetables.
Supplements containing
biofl avonoids increase
adsorption and availability
of vitamin C. Smokers
require a larger dietary
intake of vitamin C than
non-smokers, on account of
oxidative stress in their body
caused by toxins in cigarette
smoke and generally lower
blood levels.
Orange juice, grapefruit
juice, peaches, bell
pepper, citrus fruit.
Vitamin E
(tocopherol)
10 mg 1 000 mg
Recommended Dietary
Allowance*
Male:10 (mg)b
Female: 8 (mg)b
0.2–10 Doses larger than 1 000 mg
cause blood clotting, which
results in increased
likelihood of haemorrhage
in some individuals.
fortifi ed cereals, tomato
paste, sunfl ower seeds,
sh, meat, leafy
vegetables
Selenium 35 μg
55 μg****
50 μg*****
400 μg1–150*
μg/100 g
Doses larger than 200 μg can
be toxic.
Fatigue, skin disorders,
dizziness, nausea, vomiting,
anxiety and hair loss.
Brazil nuts, rockfi sh, yellow
n tuna, dairy products,
potato, rice
Zinc 15 mg 40 mg Doses larger than 25 mg may
cause anaemia and copper
defi ciency.
oysters, fortifi ed cereals,
baked beans
(Continued)
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4 B. Poljsak et al.
assessment, what might be of special interest for der-
matologists and other medical professionals. From the
Elmore s Final report (13) of the safety assessment of
L-Ascorbic Acid, Calcium Ascorbate, Magnesium
Ascorbate, Magnesium Ascorbyl Phosphate, Sodium
Ascorbate, and Sodium Ascorbyl Phosphate as used
in cosmetics it can be concluded that they function
in cosmetic formulations primarily as antioxidants.
Ascorbic Acid is used as an antioxidant and pH
adjuster in a large variety of cosmetic formulations,
over 3/4 of which were hair dyes and colors at con-
centrations between 0.3 and 0.6%. For other uses, the
reported concentrations were either very low ( 0.01%)
or in the 5 10% range. Ascorbic Acid is generally rec-
ognized as safe (GRAS) substance for use as a chem-
ical preservative in foods and as a nutrient and/or
dietary supplement. Ascorbic Acid was a photopro-
tectant in clinical human UV studies at doses well
above the minimal erythema dose (MED). One prob-
lem of vitamin C is in its instability in various topical
products, as vitamin C is prone to oxidation, and may
lose its effi cacy this way. For effective topical applica-
tion, vitamin C has to be non-esterifi ed, acidic and
optimally at 20% concentration (14).
Safety and risk assessment of tocopherol and its
compounds were published in Int J Toxicol by Zondlo
in 2002. Tocopheryl Acetate, Tocopherol, and
Tocopheryl Linoleate are used in 2673 formulations,
generally at concentrations of up to 36%, 5%, and
2%, respectively, although Tocopheryl Acetate is
100% of vitamin E oil (15). Tocopherol, Tocopheryl
Acetate, Tocopheryl Linoleate, and Tocopheryl Suc-
cinate were all absorbed in human skin. Tocopherol
is a natural component of cell membranes thought
to protect against oxidative damage. Tocopherol,
Tocopheryl Acetate, and Tocopheryl Succinate each
were reported to protect against ultraviolet radiation-
induced skin damage. These ingredients are generally
not toxic in animal feeding studies, although very
high doses ( 2 g/kg/day) have hemorrhagic activity.
These ingredients are generally not irritating or sen-
sitizing to skin or irritating to eyes, although a
Tocopheryl Acetate did produce sensitization in one
animal test, and Tocophersolan was a slight eye irri-
tant in an animal test (15). According to Burke (14),
for effective topical application, vitamin E must
be the non-esterifi ed isomer d-alpha-tocopherol at
2 5% concentration. Skin penetration experiments
showed that 55% of the topically applied α - tocopherol
accumulated in full thickness of the skin after 24
hours (16). Tocopherol acetate is very often used
antioxidant in sunscreen products.
Vitamin A derivatives are used as anti-aging ingre-
dients in cosmetics. Vitamin A is absorbed through
the skin, increases the rate of epidermal keratinocytes
turnover and collagen production, and consequently
leads to more youthful appearance of the skin (17).
Topical retinoids remain the mainstay therapy of the
photoaged skin, and their effi cacy can be noticed
Table 1. (Continued).
Nutrient Recommended daily intake*** (**)
Intakes recommended
by the FAO/WHO
Tolerable upper intake
level (UL)
Concentration in
foods (mg/100 g)
Over dosage (mg or μg/d), side-effects
and warnings Signifi cant sources
Iron 14 mg 45 mg Nausea, vomiting, abdominal pain,
diarrhea, metallic taste in the
mouth, fatigue, headache,
irritability, and lowered work
performance, skin pigmentation.
red meats, fi sh, chicken liver,
oysters
Copper 1 250 mg 10 000 mg Abdominal pain, nausea, cramps,
diarrhea, vomiting and liver
damage.
seafood (such as oysters, squid,
lobster, mussels, crab, and
clams), organ meats (such as beef
liver, kidneys, and heart), nuts
and nut butters, legumes (such as
soybeans, lentils, navy beans, and
peanuts)
* Subcommittee on the Tenth Edition of the RDAs, Food and Nutrition Board, National Research Council (1989). Recommended Dietary Allowances , 10th Ed. National Academy Press, Washington, DC.
*
* Amounts for other age and gender groups, pregnant women, lactating women, and breastfeeding infants may be much different.
*
*
* Values on labels are stated Daily Reference values (DRV) of Recommended Daily Intake (RDI). The RDI is a renewed value referring to the old Recommended Dietary Allowance (RDA).
*
*
*
* Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, DC, 2000.
*
*
*
*
* Dietar y reference intakes, Food and Nutrition Boards Institute of Medicine, National Academy Press, Washington, D.C., 1997 2004.
a Retinol equivalents .
b
α
-tocopherol equivalents.
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Skin and antioxidants 5
clinically, evaluated histologically, and measured
biochemically. Their regular use might also prevent
photoaging (18). Available topical retinoids include
tretinoin (Retin-A
®
), adapalene (Differen
®
), and
tazarotene (Tazorac
®
) and over-the-counter Retinol
®
and Retinol-A
®
. These drugs are derivatives of vitamin
A which might have anti-aging properties (19).
Discussion
It is important to pretreat the skin with antioxidants
before sun exposure. Human studies have convinc-
ingly demonstrated pronounced photoprotective
effects of natural and synthetic antioxidants when
applied topically before UVR exposure. No signifi cant
protective effect of melatonin and antioxidants (vita-
mins E and C), when applied either alone or in com-
bination, were observed when antioxidants were
applied after UVR exposure even after multiple
attempts. UVR-induced skin damage starts rapidly,
and antioxidants effectively prevent such damage only
when present in relevant concentrations, at the site of
damage, and during the oxidative stress (20). Treat-
ment of the skin with antioxidants after the UVR dam-
age might cause additional harmful effects on cell
cycle control and apoptosis process. The photoprotec-
tive effects of antioxidants are signifi cant when applied
in distinct mixtures and in appropriate vehicles. Usage
of topically applied creams/ointments with such com-
binations may improve antioxidative capacity of the
skin due to sustained antioxidative synergism. UVA-
induced skin alterations are believed to be largely
determined by oxidative processes, and topical admin-
istration of antioxidants might be particularly promis-
ing (21). However, delivery of topically applied
antioxidants through the skin is hard since they must
penetrate through the epidermal barrier to reach its
site of action and they are very unstable, what makes
them diffi cult to formulate. Antioxidants like tocoph-
erols, vitamin C, and fl avonoids are now being added
as protective agents to the skin creams. However, their
ability to penetrate deep into the skin is limited, and
their amount in the dermis might be raised by
consuming them with the diet.
Usage of topical antioxidants is favored among
dermatologists because of their broad biologic activ-
ity. Many are not only antioxidants but also possess
anti-infl ammatory and anti-carcinogenic activities,
and thus have many potential benefi ts. In general,
topical antioxidants exert their effects by down-
regulating free-radicals-mediated pathways that
damage skin (22).
Endogenous oxidative stress could be infl uenced
in two ways: by preventing ROS formation or by
quenching ROS with antioxidants. Results of epide-
miological studies on healthy volunteers, who were
treated with oral antioxidants, are inconclusive and
even contradictory: from no effect to proven either
benefi cial or harmful effect of oral antioxidant
supplements. None of the major clinical studies,
which used mortality or morbidity as an end point,
proved positive effects of supplementation with oral
antioxidants such as vitamin C, vitamin E or β -
carotene. Some recent studies showed that therapy
with antioxidants has no effect and can even increases
mortality (23 33). The intake of only one antioxidant
could alter the complex system of endogenous anti-
oxidative defence of cells or necrosis or apoptosis
pathways. It is wrong to search the » redox magic bul-
let « among different compounds with increased redox
potential. Better approach is to focus on detailed
understanding of the complex redox system of human
cells and to investigate the synergistic effects of dif-
ferent antioxidants on total oxidative stress. There are
other methods to decrease oxidative stress, e.g. pre-
vention of free radical formation at fi rst instance
(10). We have to realize that usage of synthetic vita-
min supplements is not an alternative to regular con-
sumption of fruits and vegetables. It is quite possible
that many antioxidants are still undiscovered; fur-
thermore the combination of antioxidants in fruits
and vegetables cause their reciprocal regeneration
and consecutively intensifi es their defense from free
radicals. However, defi ciency of vitamins B-12, folic
acid, B-6, C or E, or iron or zinc appears to mimic
radiation damage of DNA by causing single- and
double-strand breaks, oxidative lesions or both. Evi-
dence is accumulating that a multivitamin/mineral
supplement could improve the health of specifi c
populations, e.g. poor, young, obese, elderly and
people exposed to increased ROS from the environ-
ment, but the lack of suffi cient double-blind, multi-
centric studies does not permit recommendations on
systemic usage of antioxidants. Nevertheless, antiox-
idant-rich diets with fruits and vegetables can be
recommended without any risk. It is important to
mention that antioxidants as dietary supplements
can protect in conditions of elevated oxidative stress
and that they could be therapeutically effective in
those individuals. On the other hand, presented evi-
dences show that synthetic antioxidant supplements
cannot protect appropriately or entirely against oxi-
dative stress in situations where it is not increased
and that their usage to prevent diseases or slow aging
is controversial.
Conclusions
A wide variety of antioxidants or other phytochemi-
cals, such as licopene, coenzyme Q, glutathione, car-
nosine, selenium, zinc, biofl avonoids, green tea
polyphenols, grape seed proanthocyanidins, resvera-
trol, silymarin, genistein, and others have been
reported to possess substantial protective effects on
UV-induced skin infl ammation, oxidative stress and
DNA damage.
In order to determine oxidative stress in individu-
als, both, the ROS potential as well as the antioxidative
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6 B. Poljsak et al.
defense potential should be measured in blood or
cytosol. Numerous in vitro antioxidational potential
determinations exist that are easy to perform and
largely used in screening. It is important to recognize
oxidative imbalance in individuals early in order to
prevent the long term oxidative and antioxidative
stresses (12). These requirements should be consid-
ered when determining individuals oxidative status
before begining or ending the therapy with antioxi-
dants. Even better approach would be to monitor in
vivo the oxidative stress in skin cells. Several tech-
niques exist to assess oxidative stress in the skin and
many methods are currently under development, e.g.
electron spin resonance, fl uorescence probes, cyclic
voltammetry, but they are not routinely used (10).
From the consumers point of view, they would be
interested in the information regarding antioxidative
potential of skin products.
There is no widely accepted and standardized
method to evaluate antioxidative capacity of skin-
care products, like SPF rating system in sunscreens.
ORAC (Oxygen Radical Absorbance Capacity) and
ABEL-RAC (Analysis By Emitted Light-Relative
Antioxidant Capacity) are both accepted worldwide
as a standard measure of the antioxidative capacity
of foods, and a similar rating system could be devel-
oped for the antioxidative capacity of skin-care prod-
ucts (34). Although many methods already exist for
evaluation of skin-care cosmetic antioxidative capac-
ity, e.g. indirect spectorphotometric determination of
a free radical DPPH or ABTS (34 36), they are not
commercially available for skin-care products found
on the market. The standardization and evaluation of
antioxidative potential of skin-care products could
help consumers to choose products with effective
antioxidative properties.
Disclosures of interest: Authors have no fi nancial and
confl ict of interests to disclose. The authors alone are
responsible for the content and writing of the paper.
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... However, most recent molecular research on this problem has been restricted to UV exposure experiments on mouse or human cells in the laboratory. These studies have identified specific genes involved in antioxidant metabolism (11,12) and DNA repair (13,14) pathways that can prevent or reduce UV-induced damage. Moreover, heat-shock proteins, such as hsp70, can bind to nucleic acid repair proteins after UV exposure in yeast, which is presumed to enhance DNA repair activity (15,16). ...
... We used an irradiance of ∼3.7 mW/cm 2 UVB exposure with artificial lamps (Philips G8T5, 313 nm) in experiments, which is slightly higher than the irradiance of local conditions that N. parkeri experiences at daytime (∼3.5 mW/cm 2 ). In the pilot assesment of tolerance to UV, we exposed individuals to a continuous ∼3.7 mW/cm 2 UVB exposure up to 8 h, based on previous research (11). After 8 h of UVB exposure, we observed that skin of N. parkeri showed no obvious change, whereas stratum corneum started showing damage in N. phrynoides and Q. spinosa. ...
... Statistical Analysis of Changes to Skin Histology. We collected dorsal skin samples near the foramen magnum in a 1 cm × 1 cm square immediately after the frogs were killed and subjected them to hematoxylin-eosin staining procedures (11). The skin tissues were fixed in 10% buffered formalin overnight and subsequently preserved in 70% ethanol for storage under ambient conditions, then embedded in paraffin. ...
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Defense against ultraviolet (UV) radiation exposure is essential for survival, especially in high-elevation species. Although some specific genes involved in UV response have been reported, the full view of UV defense mechanisms remains largely unexplored. Herein, we used integrated approaches to analyze UV responses in the highest-elevation frog, Nanorana parkeri. We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. We also reveal genes related to UV defense and a corresponding temporal expression pattern in N. parkeri. Genomic and metabolomic analysis along with large-scale transcriptomic profiling revealed a time-dependent coordinated defense mechanism in N. parkeri. We also identified several microRNAs that play important regulatory roles, especially in decreasing the expression levels of cell cycle genes. Moreover, multiple defense genes (i.e., TYR for melanogenesis) exhibit positive selection with function-enhancing substitutions. Thus, both expression shifts and gene mutations contribute to UV adaptation in N. parkeri. Our work demonstrates a genetic framework for evolution of UV defense in a natural environment.
... There are, however, serious difficulties with evaluating level of oxidative stress since its different indices do not correlate with each other. 184 Furthermore, detecting the enhanced oxidative stress level in particular body fluids by specific biomarkers does not necessarily mean that certain tissues or organs are under high level of oxidative stress. ...
... 185 Therefore, standardizing different methods of measuring the redox state to establish a universal scale of oxidative stress and to determine gender-and age-specific "normal values" for each body fluid is an urgent need now. 184 In addition, implementing the innovative biotechnological platforms (e.g., nanotechnology-based strategies aimed at targeted antioxidant delivery to specific tissues or organs differing in the redox state within the body) could open new horizons for efficient healthspan-promoting antioxidant therapies. 186 ...
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The steady rise in life expectancy occurred across all developed countries during the last century. This demographic trend is, however, not accompanied by the same healthspan extension. This is since aging is the main risk factor for all age‐associated pathological conditions. Therefore, slowing the rate of aging is suggested to be more efficient in preventing or delaying age‐related diseases than treat them one by one, which is the common approach in a current pharmacological disease‐oriented paradigm. To date, a variety of medications designed to treat particular pathological conditions have been shown to exhibit pro‐longevity effects in different experimental models. Among them, there are many commonly used prescription and over‐the‐counter pharmaceuticals such as metformin, rapamycin, aspirin, statins, melatonin, vitamin antioxidants, etc. All of them are being increasingly investigated in preclinical and clinical trials with the aim of determine whether they have potential for extension of human healthspan. The results from these trials are frequently inconclusive and fall short of initial expectations, suggesting that innovative research ideas and additional translational steps are required to overcome obstacles for implementation of such approaches in clinical practice. In this review, recent advances and challenges in the field of repurposing widely used conventional pharmaceuticals to target the aging process are summarized and discussed.
... However, most recent molecular research on this problem has been restricted to UV exposure experiments on mouse or human cells in the lab. These studies have identi ed speci c genes involved in antioxidant metabolism (8, 13,14) and DNA repair (15,16) pathways that can prevent or reduce UV-induced damage. Moreover, heat-shock proteins, such as hsp70, can bind to nucleic acid repair proteins after UV exposure in yeast, which is presumed to enhance DNA repair activity (17,18). ...
Full-text available
Preprint
Defense against increasing ultraviolet radiation (UV) exposure is essential for survival, especially in high-elevation species. Although some specific genes involved in UV response have been reported, the full view of UV-defense mechanisms remains largely unexplored. Herein, we analyzed UV responses in the highest-elevation frog, Nanorana parkeri , using integrated approaches. We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. Our study revealed new UV-defense systems. Genomic and metabolomic analysis along with large-scale transcriptomic and microRNA profiling revealed a time-dependent coordinated defense mechanism in N. parkeri . Both gene mutations and expression shifts contribute to such UV adaptation. We found that microRNAs play important regulatory roles, especially in decreasing the expression levels of cell-cycle genes. Moreover, multiple defense genes (i.e., TYR for melanogenesis) exhibit positive selection with function-enhancing substitutions. Our work demonstrates a genetic framework for evolution of UV-defense in a natural environment.
... Overproduction of ROS in skin cells is one of the reasons for environmental damage of the skin. An increased level of free radicals may lead to the development of many pathologic reactions, including erythema, edema, skin aging, inflammation, allergic reactions, hypersensitivity, keratinization abnormalities, and carcinogenesis [36][37][38]. Moreover, it was found that oxidative stress was related to many cutaneous disorders, such as contact dermatitis, atopic dermatitis, scleroderma, vitiligo, acne vulgaris, psoriasis, and rosacea [10,[39][40][41]. ...
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Minocycline is a semisynthetic tetracycline antibiotic. In addition to its antibacterial activity, minocycline shows many non-antibiotic, beneficial effects, including antioxidative action. The property is responsible, e.g., for anti-inflammatory, neuroprotective, and cardioprotective effects of the drug. However, long-term pharmacotherapy with minocycline may lead to hyperpigmentation of the skin. The reasons for the pigmentation disorders include the deposition of the drug and its metabolites in melanin-containing cells and the stimulation of melanogenesis. The adverse drug reaction raises a question about the influence of the drug on melanocyte homeostasis. The study aimed to assess the effect of minocycline on redox balance in human normal melanocytes HEMn-LP exposed to hydrogen peroxide and UVA radiation. The obtained results indicate that minocycline induced oxidative stress in epidermal human melanocytes. The drug inhibited cell proliferation, decreased the level of reduced thiols, and stimulated the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). The described changes were accompanied by an increase in the intracellular level of ROS. On the other hand, pretreatment with minocycline at the same concentrations increased cell viability and significantly attenuated the oxidative stress in melanocytes exposed to hydrogen peroxide and UVA radiation. Moreover, the molecular docking analysis revealed that the different influence of minocycline and other tetracyclines on CAT activity can be related to the location of the binding site.
... Induction of inflammation, DNA damage and alterations to lipids and proteins are some of the detrimental effects of oxidative stress in human skin cells, which consequently advance to accelerated or premature ageing as well as hyper-pigmentation. Although human skin contains a pool of protective endogenous antioxidants such as catalase and glutathione peroxidase [40], exogenous antioxidants through diet and topical applications are essential to support our body's self-protection [41]. Apart from their direct protection of human skin, antioxidants are also used to preserve and protect skincare and cosmeceutical formulations from auto-oxidation caused by chemical degradation or exposure to air. ...
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Cosmeceutical formulations containing naturally derived active ingredients are currently preferred by consumers worldwide. Mushrooms are one of the potential sources for cosmeceutical ingredients but relevant research is still lacking. In this study, hot-and cold-water extractions were performed on four locally-cultivated mushrooms-Pleurotus ostreatus, Ganoderma lucidum, Auricularia polytricha and Schizophyllum commune-with the aim to assess the cosmeceutical potential of these mushroom fruitbody extracts. Total phenolics, polysaccharide and glucan content were determined. Antioxidant property of the mushroom extracts was assessed by determining the DPPH radical scavenging, ferric-reducing (FRAP) and superoxide anion (SOA) scavenging activity. Anti-hyaluronidase activity was used as an indicator for the anti-aging and anti-inflammatory property, while anti-tyrosinase activity was evaluated to assess the anti-pigmentation or whitening property of these extracts. Our results showed that total polysaccharide content of P. ostreatus extracts was the highest (235.8-253.6 mg GE/g extract), while extracts from G. lucidum contained the lowest glucan (10.12-10.67%). Cold-water extract from S. commune exhibited substantial tyrosinase inhibition activity (98.15%) and SOA scavenging activity (94.82%). The greatest hyaluronidase activity was exhibited by G. lucidum hot-water extract, with the value of 72.78%. The findings from the correlation analyses suggest that the cosmeceutical properties of these mushrooms can be attributed mainly to the combination of different types of compound such as polysaccharides and phenolics. Overall, cold-water extract of S. commune and hot-water extract of G. lucidum showed the best results and may be further investigated.
... After this incident, the skin becomes clinically explicit with age, and functional harm to the skin prevails. At the moment, it becomes necessary to consume supplementary antioxidants or to apply them on the skin in topical preparations (Poljsak et al. 2013). Vitamin C is a water-soluble vitamin and presents in the skin predominantly that helps in protection of aqueous phase of the cells. ...
Full-text available
Chapter
Human skin is the largest organ of the body and it provides the first line of the defense system against environmental factors coming in contact by evading our ecosystem. Skin possesses notable regeneration capacity due to the presence of different types of stem cells including epithelial stem cells, melanocyte stem cells, mesenchymal stem-like cells, and progenitor cells. Moreover, the integrity of the skin is mainly maintained by epidermal stem cells. Skin and skin stem cells are more vulnerable toward aging process due to their direct contact with external stimuli including environmental pollutants, infection, and UV irradiation. Aging is a complex and multifactorial process mainly caused by imbalanced redox status, DNA mutation, and telomere shortening. The reactive oxygen species (ROS) overproduction is the major contributor of skin aging as ROS exert oxidative damage to macromolecules and cell organelles, which continuously accumulate and further accelerate aging process. Additionally, UV irradiation induces oxidative stress, overproduction of ROS, and DNA damage which collectively cause photoaging of the skin. This chapter summarizes the overall effects of oxidative stress on skin aging, and several antiaging strategies such as supplementation of nutritional antioxidants and autophagy modulation are also described to slow down the aging process of skin as well as skin diseases.
... After this incident, the skin becomes clinically explicit with age, and functional harm to the skin prevails. At the moment, it becomes necessary to consume supplementary antioxidants or to apply them on the skin in topical preparations (Poljsak et al. 2013). Vitamin C is a water-soluble vitamin and presents in the skin predominantly that helps in protection of aqueous phase of the cells. ...
Chapter
In last few years, average life expectancy of humans has increased globally. Exposure to hazardous chemicals, ultraviolet (UV) radiation and other carcinogens has also increased the cancer burden in humans. Skin cancer is mainly associated with the DNA damage because of the prolonged exposure to UV radiation. Several structural changes, mutations and amplifications of oncogenes have been reported in skin cancer. The continuous development of bioinformatics approaches, next-generation sequencing, proteomics, transcripts, and epigenetic analysis has increased the understanding of cancer progression and molecular mechanisms and to design appropriate drug for the diseases. In this chapter, we have discussed the importance of bioinformatics in understanding the molecular mechanisms of skin cancer progression, related signaling pathways, data analysis, and drug development.
... Однако для поддержки этих систем зачастую необходима местная аппликация различных антиоксидантов. Более того, некоторые антиоксиданты при местном применении оказывают противовоспалительное и антиканцерогенное действие [42,43]. ...
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The review focuses on the possibilities and prospects of the use of fullerenes and their derivatives in cosmetics, the only industrial area where fullerenes have found practical application today. Based on the literary data and the results of their own experiments, the authors substantiate the safety of using fullerene for living organisms, as well as the usefulness of introducing fullerene as antioxidant in cosmetic compositions. Other useful properties of fullerene used in cosmetics and dermatology are discussed.
Chapter
Antioxidants are substances that fight free radicals produced in the body due to several intrinsic as well as extrinsic factors such as pollution, smoking, UV radiation, etc. They play a preventive as well as scavenging role in removing the excess free radicals thereby preventing oxidative stress. Oxidative stress is capable of disturbing the normal body physiology and may cause lethal diseases such as cancer, Alzheimer’s, diabetes, etc. The antioxidants have an important role to play with the rapid increase in the external forces causing uncontrolled generation of free radicals. The human body produces its own antioxidants, called endogenous antioxidants. However, some antioxidants are obtained from external sources; these exogenous antioxidants fulfill the dietary requirements of the body. In the present chapter, natural as well as synthetic antioxidants have been discussed with special emphasis on plant-derived antioxidants and their potential applications in the treatment and management of life-threatening diseases. Plants being an all-natural hub for antioxidants have been discussed for their safer use, variety, and dosage. In addition to this, the role of antioxidants in the food, packaging, and cosmetics industry has also been highlighted. This chapter sums up the potential applications as well as working of antioxidants while underscoring its future prospects for further study.
Article
Background Experimental and observational data suggest that micronutrients with antioxidant capabilities may retard the development of age-related cataract. Objective To evaluate the effect of a high-dose antioxidant formulation on the development and progression of age-related lens opacities and visual acuity loss. Design The 11-center Age-Related Eye Disease Study (AREDS) was a double-masked clinical trial. Participants were randomly assigned to receive daily oral tablets containing either antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) or no antioxidants. Participants with more than a few small drusen were also randomly assigned to receive tablets with or without zinc (80 mg of zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as part of the age-related macular degeneration trial. Baseline and annual (starting at year 2) lens photographs were graded at a reading center for the severity of lens opacities using the AREDS cataract grading scale. Main Outcome Measures Primary outcomes were (1) an increase from baseline in nuclear, cortical, or posterior subcapsular opacity grades or cataract surgery, and (2) at least moderate visual acuity loss from baseline (≥15 letters). Primary analyses used repeated-measures logistic regression with a statistical significance level of P = .01. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. Results Of 4757 participants enrolled, 4629 who were aged from 55 to 80 years had at least 1 natural lens present and were followed up for an average of 6.3 years. No statistically significant effect of the antioxidant formulation was seen on the development or progression of age-related lens opacities (odds ratio = 0.97, P = .55). There was also no statistically significant effect of treatment in reducing the risk of progression for any of the 3 lens opacity types or for cataract surgery. For the 1117 participants with no age-related macular degeneration at baseline, no statistically significant difference was noted between treatment groups for at least moderate visual acuity loss. No statistically significant serious adverse effect was associated with treatment. Conclusion Use of a high-dose formulation of vitamin C, vitamin E, and beta carotene in a relatively well-nourished older adult cohort had no apparent effect on the 7-year risk of development or progression of age-related lens opacities or visual acuity loss.
Article
OBJECTIVE: To estimate the association between antioxidant use and primary cancer incidence and mortality and to evaluate these effects across specific antioxidant compounds, target organs, and participant subgroups. METHODS: Multiple electronic databases (MEDLINE, Cochrane Controlled Clinical Trials Register, EMBASE, Science Citation Index) were searched from their dates of inception until August 2005 to identify eligible randomized clinical trials. Random effects meta-analyses estimated pooled relative risks (RRs) and 95% confidence intervals (CIs) that described the effect of antioxidants vs placebo on cancer incidence and cancer mortality. RESULTS: Twelve eligible trials, 9 of high methodological quality, were identified (total subject population, 104,196). Antioxidant supplementation did not significantly reduce total cancer incidence (IRR, 0.99; 95% CI, 0.94-1.04) or mortality (RR, 1.03; 95% CI, 0.92-1.15) or any site-specific cancer incidence. Beta carotene supplementation was associated with an increase in the incidence of cancer among smokers (RR, 1.10; 95% CI, 1.03-1.10) and with a trend toward increased cancer mortality (RR, 1.16; 95% CI, 0.98-1.37). Selenium supplementation was associated with reduced cancer incidence in men (RR, 0.77; 95% CI, 0.64-0.92) but not in women (IRR, 1.00; 95% CI, 0.89-1.13, value for interaction, P<.001) and with reduced cancer mortality (RR, 0.78; 95% CI, 0.65-0.94). Vitamin E supplementation had no apparent effect on overall cancer incidence (RR, 0.99; 95% CI, 0.941.04) or cancer mortality (RR, 1.04; 95% CI, 0.97-1.12). CONCLUSION: Beta carotene supplementation appeared to increase cancer incidence and cancer mortality among smokers, whereas vitamin E supplementation had no effect. Selenium supplementation might have anticarcinogenic effects in men and thus requires further research.
Article
It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes. METHODS: 20,536 UK adults (aged 40-80) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) or matching placebo. Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants. An average of 83% of participants in each treatment group remained compliant during the scheduled 5-year treatment period. Allocation to this vitamin regimen approximately doubled the plasma concentration of alpha-tocopherol, increased that of vitamin C by one-third, and quadrupled that of beta-carotene. Primary outcomes were major coronary events (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity. FINDINGS: There were no significant differences in all-cause mortality (1446 [14.1%] vitamin-allocated vs 1389 [13.5%] placebo-allocated), or in deaths due to vascular (878 [8.6%] vs 840 [8.2%]) or non-vascular (568 [5.5%] vs 549 [5.3%]) causes. Nor were there any significant differences in the numbers of participants having non-fatal myocardial infarction or coronary death (1063 [10.4%] vs 1047 [10.2%]), non-fatal or fatal stroke (511 [5.0%] vs 518 [5.0%]), or coronary or non-coronary revascularisation (1058 [10.3%] vs 1086 [10.6%]). For the first occurrence of any of these "major vascular events", there were no material differences either overall (2306 [22.5%] vs 2312 [22.5%]; event rate ratio 1.00 [95% CI 0.94-1.06]) or in any of the various subcategories considered. There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause. INTERPRETATION: Among the high-risk individuals that were studied, these antioxidant vitamins appeared to be safe. But, although this regimen increased blood vitamin concentrations substantially, it did not produce any significant reductions in the 5-year mortality from, or incidence of, any type of vascular disease, cancer, or other major outcome.
Chapter
Human skin aging is caused by a number of factors. One of the most important and influential factors is the exposure of the skin to UV radiation, which leads to the damage of the skin's structure and integrity. UV radiation is responsible for up to ninety percent of visible skin aging. However, the effects of the sunlight on the skin include not only dryness, loss of elasticity, wrinkles, discoloration and changes in texture, but also increased incidence in various precancerous conditions and skin malignancies.
Article
Background: It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes. Methods: 20,536 UK adults (aged 40-80) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) or matching placebo. Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants. An average of 83% of participants in each treatment group remained compliant during the scheduled 5-year treatment period. Allocation to this vitamin regimen approximately doubled the plasma concentration of alpha-tocopherol, increased that of vitamin C by one-third, and quadrupled that of beta-carotene. Primary outcomes were major coronary events (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity. Findings: There were no significant differences in all-cause mortality (1446 [14.1%] vitamin-allocated vs 1389 [13.5%] placebo-allocated), or in deaths due to vascular (878 [8.6%] vs 840 [8.2%]) or non-vascular (568 [5.5%] vs 549 [5.3%]) causes. Nor were there any significant differences in the numbers of participants having non-fatal myocardial infarction or coronary death (1063 [10.4%] vs 1047 [10.2%]), non-fatal or fatal stroke (511 [5.0%] vs 518 [5.0%]), or coronary or non-coronary revascularisation (1058 [10.3%] vs 1086 [10.6%]). For the first occurrence of any of these "major vascular events", there were no material differences either overall (2306 [22.5%] vs 2312 [22.5%]; event rate ratio 1.00 [95% CI 0.94-1.06]) or in any of the various subcategories considered. There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause. Interpretation: Among the high-risk individuals that were studied, these antioxidant vitamins appeared to be safe. But, although this regimen increased blood vitamin concentrations substantially, it did not produce any significant reductions in the 5-year mortality from, or incidence of, any type of vascular disease, cancer, or other major outcome.