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Paper text:
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 ) .
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 ) .
later this theory was expanded to include other diseases such as malignancies , vitiligo , alzheimer 's disease , atherosclerosis etc .
free radicals are compounds formed when oxygen molecule combines with other molecules yielding an odd number of electrons .
the molecules which are oxygen - centred are ros and those which have nitrogen are reactive nitrogen species ( rns ) . 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 ] .
free radical formation and antioxidant quenching the free radical the important ros are superoxide anion ( o2 ) , peroxide , hydroxyl radical ( oh ) , hydroxyl ion , and singlet oxygen ( o2 ) .
nitric oxide ( no ) and peroxynitrite ( onoo ) are the major rns in biological systems .
exogenous sources of ros are air pollutants , ozone , radiation , chemicals , smoking , toxins , and pathogenic microorganisms .
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 .
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 .
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 .
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 .
various pathogenic mechanisms are responsible for these lesions such as induction of transcription factors that includes activator protein ( ap-1 ) and nuclear factor b ( nf-b ) 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 .
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 ,
commonly used antioxidants in dermatology are classified as endogenous and exogenous [ table 1 ] .
general classification of antioxidants 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 .
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 , -tocopherol , squalene , and coenzyme q10 , distributed in a gradient with the highest concentration on the deepest cornified envelope layers . summary of important antioxidants is given in table 2 .
summary of important antioxidants 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 .
beverages and antioxidant composite index 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 .
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 . 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 . on the positive side ,
few recent studies have also shown that combining various antioxidants can have a synergistic action .
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 .
beverages and antioxidant composite index 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 .
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 .
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 . on the positive side , few recent studies have also shown that combining various antioxidants can have a synergistic action .
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 .
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 .