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Author(s): Shweta Ramkar, Hemendra Kumar Sahu, Narayan Hemnani, Ravi Parashar, Preeti K. Suresh


Address: University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India.
*Corresponding Author:

Published In:   Volume - 35,      Issue - 2,     Year - 2023

Cite this article:
Shweta, Sahu, Hemnani, Parashar and K. Suresh (2022). Oxidative stress: Insights into the Pathogenesis and Treatment of Alopecia. Journal of Ravishankar University (Part-B: Science), 35(2), pp. 44-61.

Oxidative stress: Insights into the Pathogenesis and Treatment of Alopecia

Shweta Ramkar, Hemendra Kumar Sahu, Narayan Hemnani, Ravi Parashar, Preeti K. Suresh*

University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India.

*Corresponding Author:


Hairs are exposed to a host of endogenous and environmental stress by pollutants, microbial assaults, UV radiation, oxidized scalp lipids, grooming practices and cosmetic treatments which have diverse range of adverse consequences. The exposure to these environmental and cosmetic substances, leads to generation of free radicals, reactive oxygen species in particular, leading to oxidative stress. Oxidative stress generates inflammation, and/or psycho-emotional stress, and also influences the ageing process, including the hair follicle. The term alopecia signifies loss of hair owing to several factors, ultimately resulting in decreased hair density. Cell death on hair follicle (keratinocytes and its distinctive mesenchyme of dermal papilla) have been attributed to mechanisms of oxidative stress, including H2O2, nitric oxide and derivatives, ultraviolet rays, ionizing radiations, endotoxin-induced inflammation, photodynamic therapy and cigarette smoke. Persistent oxidative activities in the body, may generate antioxidant defense systems, which can prevent the attack of biological molecules. In case of androgenic alopecia, copper and zinc was discovered in the disrupted metabolism form in serum, urine and hair of the patients, and data suggests rise in oxidative stress. This review is focused on the effects of the reactive oxygenated species in disturbing the redox balance and inducing oxidative injury that leads to androgenic alopecia.


Keywords: Hair Follicle, Oxidative Stress, Antioxidants, Reactive Oxygen Species, Redox Balance.



Oxidative stress is caused by the imbalance between the production of free radicals and ability of the body to counteract or detoxify their harmful effects through neutralization by antioxidants, leading to tissue damage (Haslam et al., 2016). Free radicals are the atom or the group of atoms that contain unpaired electron and are formed during a number of biochemical reactions (Suresh et al., 2013). They are highly reactive and may cause damage to macromolecules like DNA, protein, lipid, enzymes, etc. They are also known as reactive oxygen species (ROS). Antioxidants are one of the defensive strategies that assist in controlling the level of free radical and prevent the oxidation of biomolecules. Oxidative stress have been implicated in a number of human pathologies including neuro-degenerative disorders, chronic kidney disease, skin aging and common dermatoses such as psoriasis (Richter et al., 2015; Wagener et al., 2013; Haslam et al., 2016, Suresh et al., 2014). Oxidative stress is reported to be one of the key influences leading to hair loss as it is linked with a number of factors that increase cellular oxidative stress, including smoking, alcohol consumption, some metabolic syndrome, and UV radiation (Upton et al., 2015; Gao and Dalton, 2007). Some of the common examples of enzymatic antioxidants in alopecia include superoxide dismutase, catalase, glutathione peroxidase, paroxone, nemoxigenase and thioredoxin reductase. Non-enzymatic antioxidants include glutathione, vitamin E and beta-carotene. In excess amount, the antioxidants may damage protein structure (Yasuko et al. 1994). The reaction of human organs on oxidative damage and how they control redox insult is of significant physiological and clinical relevance.



Androgenic alopecia (AGA) is a common hair loss dysfunction and is also referred to as hereditary/genetic hair loss. Accordingly, there are two conditions viz., male pattern baldness (MPB) and female pattern baldness (FPB). It may occur as early as in the late teens or occasionally in early twenties. The phenotypical changes are produced when 5-alpha reductase enzyme starts transforming the testosterone hormone into its derivative, dihydrotestosterone (DHT) which induces the miniaturization of the hair follicles and the hair cycle changes, and ultimately hair no more extrudes through the skin ( Prie et al., 2016). Mantel et. al. (2017) reported that substantial levels of prostaglandin-D2 was present in the bald scalp of AGA patients and it functionally inhibits the hair growth (Mantel et al., 2017). Alopecia areata (AA) is an autoimmune disorder with body's own immune system assaulting the healthy hair follicles leading to patchy hair loss on the scalp. The actual explanation for generation of AA remains unclear, however it is commonly assumed to be induced by stress and stressful events. In certain situations, AA can advance throughout the entire scalp, and this is termed as alopecia totalis (AT). In alopecia universalis (AU), significant hair loss occurs across the entire body, including eyebrows (Islam et al., 2015). In cicatricial alopecia (CA) or scarring alopecia hair follicles are damaged and replaced by scar tissue. In case of primary CA, hair loss occurs owing to direct inflammation of the hair follicles. Secondary CA usually refers to scarring hair loss (such as burns or infections), and ensues as a result of an event or process unrelated to the follicles. Traction alopecia (TA) is a distinct kind of alopecia and is frequently produced directly by the action of the individual, which results in excessive stress on the hair and breakdown (Price and Colombe, 1996). It may be caused by traumatic hair styles (e.g., braiding, tight ponytails and frequent hair treatment with chemicals (e.g., hair coloring and bleaching). Exposure to allergens, irritants, toxins, burns, injuries, and infection as well as certain medication (especially antibiotics, testosterone), chronic kidney failure, radiation and chemotherapy and malnutrition have also been attributed to the generation of alopecia (Ramkar et al., 2020).



Antioxidants are the substances that prevent or inhibit the factors that lead to oxidative injury in the cell. When an antioxidant reacts with a free radical, antioxidant itself becomes oxidized. Therefore, the antioxidant resources must be regularly stored in the body. Antioxidants perform diverse roles in different systems, for instance an antioxidant effective against free radicals in one particular system may be ineffective in other systems. Also, in certain situations, these antioxidants may even act as a pro-oxidant as it can generate toxic ROS/RNS (Abdel et al., 2011). The antioxidant process can function in one of the two ways, viz., it can break or prevent the chain reaction or assist in disintegrating into a harmless product. In the chain-breaking process, when a radical is released or steals an electron, a second radical is formed. In this continuous process, the last one exerts the same action on another molecule until the free radical does not form a stable compound by a chain-breaking antioxidant, or it is simply converted into an innocuous product (Ryter et al., 2007). The classic example of such a chain reaction is lipid peroxidation. An antioxidant enzyme like superoxide dismutase, catalase and glutathione peroxidase can prevent oxidation by reducing the rate of chain initiation, e.g., either by scavenging initiating free radicals or by stabilizing transition metal radicals such as copper and iron (Akar et al., 2002).



Populations of pluripotent stem cells are responsible for regulation of hair follicle development as well as hair growth and are present in dermal papilla (DP). In DP cells (DPCs), attachment of androgen in androgenic receptors is believed to be action on hair growth regulation. Studies indicate that in greying follicles, ROS was produced by the melanocytes and it might be a reason for creating an oxidative environment in the surrounding follicular area that could affect DPCs especially in balding scalp (Driskell et al., 2013; Hunt and McHale, 2005). As depicted in Fig.1 free radical causes the oxidative damage to hair follicle stem cells or dermal papilla cells in epithelial bulge, which are responsible for the repetitive growth of hair follicle during hair cycle (Arck et al., 2006).


Fig. 1: Sequential events in pathogenesis of alopecia


Ultraviolet (mainly UV-B) radiation attacks the keratin (hair protein fractions) and melanin pigments. On the surface of the cuticle and inside the hair fibre, disulfide bonds are present that are broken by UV-B radiation leading to denaturation of the hair structure. On the other hand, UV-A radiation generally produces ROS via interaction with endogenous photo sensitizers (Fernández et al. 2012). Fig. 2 demonstrates the cellular damage in hair follicle.

Fig. 2: Schematic illustration of the UV-induced alopecia


Alopecia may be a fall out of radiation therapy, chemotherapy, stem cell transplantation, and targeted therapy. These therapies can cause hair loss by damaging the cells that promote hair growth. Hair loss may occur throughout the body, including the head, face, arms, legs, underarms, and pubic area (Ramkar et al.,2022). Hair may come out entirely, slowly, or in parts. Or, hair will simply become thin, sometimes unnoticeably and may become duller or dryer. Hair loss associated with cancer therapy is usually transitory. Most of the time, hair will grow back, however infrequently, it may remain thin (Gilhar et al., 2016; Harman, 2002). Some of the drugs likely to cause hair loss or thinning are listed in Table 1.


Table 1- Drugs with oxidant properties


Brand name












Adriamycin, Doxil












Multiple brand names


Marqibo, Vincasar


Alocrest, Navelbine



The nutrient antioxidant deficiency is one of the major factors, which can cause numerous chronic and degenerative pathologies. Hair growth can be maintained by the combination of nutrients delivered to the hair roots and good health. It is also affected by the androgens enzyme blockers without the possibility of side effects from the use of hair loss medications ( Sinbad et al., 2019). Right choice of antioxidants, minerals, vitamins, and amino acids may promote hair growth. However, excess use of antioxidants, vitamin A, vitamin E, omega 3 can cause hair loss instead of hair growth (Rutkowski and Grzegorczyk, 2012; Timbo et al., 2006; Rajput, 2017). There are number of nutrients present in the body that have unique structure and antioxidant function (Radimer et al., 2004).


Table 2- Mechanism of action of various nutrients




B group


The role of vitamin B5 in hair loss is not clear, but it might assist in improvement of cellular metabolism and can provide benefits to hair. Vitamin B6 is also critical in skin building and growth, and also contributes in cysteine incorporation within hair cells. Thiamine (B1), riboflavin (B2) and vitamin B12 also play a role in maintaining healthy hairs.

(D’Agostini et al., 2007; Rushton, 2002)


An important cofactor in the normal function of enzymes in carboxylation. Deficiency of biotin may lead to conjunctivitis, skin rashes and alopecia.

(Wolf, 2020)


Has a significant enzymatic role in the formulation of collagen fibers and crosslinks in elastin, in the production of di-sulfide bonds between cysteine molecules in cytoskeletal proteins of cortical and cuticle proteins in post-translational phase. Hence, it may have some role in hair biology, which is not clearly understood.

(Galbraith, 2014)

Cysteine and Methionine

The use of cysteine along with methionine promotes the repair of structural graze of hair as well slows down the hair loss. They contribute to the evasion of oxidative stress that can stop the hair loss, and favor the formation of natural antioxidants like glutathione.

(Clementeet al., 2018; Trüeb, 2009)

Folic Acid

Folate is a water-soluble vitamin (vitamin B6), and comprises of naturally occurring dietary folate and folic acid. Folate is a coenzyme that aids in the production of nucleic acids and in amino acid metabolism.

(Almohanna et al., 2019)


Niacin (vitamin B3) is a vital component for the body, aids in the generation of ATP and thus an energy support for the cells. Its insufficiency leads to pellagra, as well as diarrhea, weakness, dermatitis, hyper pigmentation and hair loss.

(Guo and Katta, 2017)


Selenium is an essential trace element; it plays a functional role to protection to the hair from oxidative damage as well as it provides hair follicle morphogenesis.

(Tinggi, 2008)


Taurine, a beta-amino acid, is found to have an important character to provide a proper function and maintenance of nervous system and muscle structure. Hence, it can be used as a counter androgenetic alopecia, by limiting the process of follicular weakening.

(Collin et al., 2006)

Vitamin C

Vitamin C is a water-soluble antioxidant, helpful to decrease the oxidative stress responsible for the hair follicle degeneration. In the formation of collagen and as supporting element in the cross-linking of keratin fibers by enzymatic reaction, vitamin C plays a crucial role as a cofactor.

(Finner, 2013; Padayatty et al., 2003)


Zinc plays an essential role in several metabolic pathways and cellular functions. Additionally, it helps in the production of keratin, which is the main component (about 95%) of the hair structure. Zinc accelerates hair follicle recovery and is inhibitor of hair follicle regression.

(Kilet al., 2013)


Vitamin E

Vitamin E is a fat-soluble vitamin with high antioxidant potency. It is a chiral compound with eight stereoisomers: α, β, γ, δ tocopherol and α, β, γ, δ tocotrienol. In humans, only α-tocopherol is the bioactive form. α-tocopherol safeguards the membranes around the cell from damage by free radicals owing to its fat-soluble properties (Heyland et al., 2005; Sinbad et al., 2019). Studies have indicated that vitamin E may have preventive action against breast, prostate and colon cancers, ischemia, some cardiovascular diseases, arthritis, cataract and certain neurological disorders. Cooking and storage may destroy the natural d-α-tocopherol in foods (Devasagayam et al., 2004).


Vitamin C

Vitamin C or ascorbic acid is a water-soluble vitamin, and have been implicated in the formation of carnitine collagen and neurotransmitters biosynthesis. They are antioxidant, anti-atherogenic, anti-carcinogenic and immunomodulator (Yadav et al., 2016). It has also demonstrated reduction in the incidence of stomach cancer, colorectal and lung cancer. Vitamin C and vitamin E act synergistically to reduce free radicals and also regenerates the reduced form of vitamin E. However, the intake of high doses of vitamin C (2000 mg or more/day) has been the subject of debate for its eventual pro-oxidant or carcinogen property (Hatem et al., 2018; Labrozzi, 2020).



Beta-carotene is a pro-vitamin and converts into the active form i.e. vitamin A, a fat soluble member of the carotenoids. Beta-carotene is converted to retinol, which is essential for vision. It acts as antioxidant by quenching of singlet oxygen (Yadav et al., 2016).



Selenium is a trace mineral found in vegetables, liver, meat, water, sea food, soil, and yeast. It helps to form the active site of several antioxidant enzymes like glutathione peroxidase (Finner, 2013). At low dose, it acts as an antioxidant, anti-carcinogenic and immunomodulator. But at higher doses it produces selenosis which is a selenium poisoning characterized by gastrointestinal disorders, hair and nail loss, cirrhosis, pulmonary edema and death (Heyland et al., 2005).



Flavonoids are polyphenolic compounds present in most of the plants. Based on the chemical structure, more than 4000 flavonoids have been acknowledged and categorized into flavanols, flavanones, flavones, isoflavones, catechins, anthocyanins, proanthocyanidins. Because of their potent antioxidant activity, they are reported to prevent or delay a number of chronic and degenerative disorder such as cardiovascular diseases, cancer, memory loss, arthritis, cataract, aging, stroke, inflammation, Alzheimer’s disease, infection. Every plant contains a distinctive amalgamation of flavonoids and every plant shows very different effects on the body. The natural sources of flavonoids include green tea, grapes, apple, cocoa, ginkgo biloba, soybean, curcuma, berries, onion, broccoli, etc. For example, green tea is a rich source of flavonoids, especially flavanols (catechins) and quercetin. Catechin levels are 4-6 times greater in green tea than in black tea. Many health benefits of green tea reside in its antioxidant, anticarcinogenic, antihypercholesterolemic, antibacterial (dental caries), anti-inflammatory activities (Sathishkumar et al., 2016; Kaushik et al., 2011).



Cytochrome-P450 is involved in Reactive Oxygen Species (ROS) generation during phase-I of drug metabolism (Deavall et al., 2012). Substrate binding to CYP-450 occurs via the combination of one molecule of oxygen to the enzyme leading to the formation of an oxy complex (Thiboutot et al., 2003). The oxy complex thus formed is again reduced to peroxy complex that accepts two protons and produce water through intermediate reactions. Since ROS is generated during the intermediate stages of CYP-mediated biotransformation of drugs, their continuous production results in NADPH consumption by the CYP molecules (Abdel et al., 2011; Ogun, 2015). Although it was mentioned earlier that ROS is generated during the reaction of CYP-450 with its substrate, the electron-transfer chain of microsome continues to oxidize NADPH and produce ROS even in the absence of any substrate (Maxson and Mitchell, 2016). This excessive ROS generation leads to repression of CYP gene expression (Fig. 3) (specifically CYP-1A1 gene expression) is through the inactivation of the transcription factor, nuclear factor-1. Enzymes like ipoxygenase, cyclooxygenase and xanthine oxidase can also contribute to ROS production (Held, 2015; Snezhkina et al., 2020).


ROS generated during biotransformation of drugs consists of hydrogen peroxide, hydroxyl and superoxide radical. The hydroxyl radical is very reactive and can modify nitrogenous bases of DNA leading to DNA strand breakage. These ROS, particularly superoxide radical, gets protonated to form perhydroxyl radical. This radical plays a significant role in lipid peroxidation and membrane destabilization (Abdel et al., 2011). These reactive species also reacts with nitric oxide (NO) forming peroxynitrite ion (ONOO) and exerting deleterious effect on DNA, protein and lipid molecule (Koca et al., 2005; Wolf et al., 2003). Peroxisome is also a source of hydrogen peroxide but catalase present in this organelle decomposes it into water and oxygen creating a fine balance at physiological condition.


Fig. 3: Flow chart depicting CYP mediated ROS generation and transcriptional repression of CYP



Most of the drugs and xenobiotics, to which human beings are exposed, generate quinone metabolites. Quinones are involved in electron transport. Quinone-quinol cycle leads to oxidative stress leading to devastating effect. Many drugs are converted to quinone metabolites during biotransformation (Deavall et al., 2012). These quinone metabolites are reactive molecular species which forms adducts with macromolecules, anti-oxidant molecules like GSH and deplete the pool of antioxidant molecule like GSH thereby generating more ROS (Fig. 4). Excessive ROS generation and sequestration of endogenous antioxidant species lead to oxidative stress. Prolonged persistence of cellular stress causes sustained activation of stress responsive MAPKs ultimately manifesting into cell death (Schiffer et al., 2018).

Fig. 4: Flow chart depicting mechanism of drug metabolism induced cellular stress


Table 3- Oxidative stress producing drug metabolites

S. No.






Drug of SERM is a well-known anticancer agent, undergoes hydroxylation to 4-Hydroxytamoxifen catalyzed by CYP2D6. This 4-Hydroxytamoxifen gets oxidized via P450 mediated oxidation to para-quinone methide that forms stable adducts with nitrogen bases of DNA.

(Garg et al., 2016; Bhise et al., 2017)



This is a frequently prescribed antipsychotic drug, oxidative bioactivation of this drug by CYP450 families generates reactive nitrite ion, clozapine-N-oxide. These reactive intermediates generated during metabolism, cause ROS formation and impose oxidative stress.

( Fehsel et al.,

2005; Microglial et al., 2011)



Berberine is the most abundant protoberberine alkaloid. CYP enzymes, namely CYP2D6, CYP1A2 and CYP3A4, contribute to oxidative metabolism of this alkaloid and play a major role in the generation of berberine metabolites like demethyleneberberine, thalifendine.

(Park et al., 2015)




Doxorubicin is a widely used anticancer drug. It can also generate free radical formation which generates oxidative stress in cancer cell. The cycling process between quinone and semiquinone forms generates a huge amount of superoxide radical (O2-). This in turn produces a variety of active ROS/RNS species, including H2O2OH, and ONOO-.

(Kim et al., 2006; Cappetta et al., 2017)




This is the most popularly used 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. The oxidative metabolism of atorvastatin and generation of reactive metabolites must be considered for a reliable prediction of drug disposition.

(Najah et al., 2008; Wassmann et al., 2002)


Hair follicle comprises of the epithelium of keratinocytes and a group of specified mesenchymal cells called dermal papilla. Developmental morphogenesis and postnatal growth of hair follicles are build-up with characteristic structure of epithelial-mesenchymal interaction (EMI) of these two groups of cells (Huang et al., 2017). Elevated levels of prostaglandin D2 (PGD2) have been shown to be present in the bald scalp of androgenic alopecia (AGA) patients and to functionally inhibit hair growth.



Oxidative stress was supposed to be one of the important causative agents of androgenic alopecia, which is characterized by excessive scalp hair thinning. Hence, it can be suggested that the utilization of antioxidant molecules with some functional excipients can stop the progression of this disease (Hatem et al., 2018). Hair loss rarely needs to be treated. Many people seek treatment for cosmetic reasons, but there is no cure for alopecia and no universally proven therapy to induce hair growth. Although there are some drugs useful in alopecia and these include finasteride, minoxidil, and corticosteroids.



Finasteride and dutasteride are the drugs available in the market as tablet. A synthetic type II-5α reductase inhibitor can reduce the conversion of testosterone to DHT as demonstrated in Fig. 5. If it is taken for over 6 months to 1 year, at a dose of 1 mg daily, it can improve the hair count and thickness, with enhanced response. The efficacy of dutasteride 2.5 mg/day was superior to that of finasteride 5 mg/day (McElwee and Shapiro, 2012; Kaufman et al., 1998). Finasteride is reported to exhibit some side effects related to sexual functions. On continuous oral administration for long term, there can be loss of hairs, which was gained within 12 months. It is also reported to be less effective on large bald spots (Guo et al., 2017; Yu et al., 2006).

Fig. 5: Mechanism of action of finasteride



Minoxidil was originally employed as antihypertensive therapy and improved the blood circulation in particular area of hair follicles and has been consequently used as a topical treatment for hair loss and is available as 2% and 5% solutions. Minoxidil use is associated with angiogenesis, vasodilation, and enhanced cell proliferation, probably mediated via potassium channel opening. Minoxidil produces some side effects when it comes in contact to skin with dermatitis and a transitory shedding with starting first 4 months of use. It helps to increase blood flow to hair follicles by dilating the blood vessels via increasing K+ channel (Fig. 6). Hence, it provides more nutrients to the hair follicle and promotes growth (Kumar et al., 2018; Sheikh et al., 2015; Bilandi et al., 2017).


Fig. 6: Mechanism action of minoxidil


Corticosteroids act by suppressing immune system. This is useful in androgenic alopecia because the condition is thought to be caused by the immune system damaging the hair follicles.


Other medications

Caffeine is used in the treatment of hair loss and stimulation of hair growth. It also inhibits phosphodiesterase (PDE) that is responsible for degradation of cAMP. This increases intracellular levels of cAMP and stimulates cellular metabolism. Furthermore, caffeine causes vasodilation and, thereby, increases blood supply to the follicles (Ramezani et al., 2018). Cyclosporin's main effect is to lower the activity of T-cells; it does so by calcineurin–phosphatase pathway and preventing the mitochondrial permeability transition pore from opening (López-Ongil et al., 1998). Cyclosporin binds to the cytosolic protein cyclophilin (immunophilin) of lymphocytes, especially of T cells. This cyclosporin—cyclophilin complex inhibits calcineurin, normally responsible for activation of transcription of interleukin-2. In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin. Calcineurin then dephosphorylates the transcription factor NF-AT (nuclear factor of activated T-cells), which moves to the T-cell nucleus and increases the transcription of genes for IL-2 and related cytokines. Cyclosporin, by preventing the dephosphorylation of NF-AT, leads to reduced effector T-cell function; it does not affect cytostatic activity (Chen et al., 2002; López-Ongil et al., 1998; Pérez de Hornedo et al., 2007). In case of sulfasalazine, sulfapyridine splits off in colon by bacterial action and active compound (5-ASA is active in ulcerative colitis) absorbed systemically and generation of superoxide radicals and cytokine liberation is suppressed (Kim et al., 2009; Couto et al., 2010). Methotrexate is a folate antagonist and is a potent immunosuppressant which markedly depresses cytokine production and cellular immunity, and has anti-inflammatory property. Azathioprene is a prodrug and is converted to 6-mercaptopurine (Elelaimy et al., 2012), that inhibit de novo purine synthesis and causes DNA damage that inhibit proliferation of T cell (Bhandaru et al., 2012).



The issues related to the hair including reduction in hair production (alopecia) and decreases in hair coloration (greying) have been focal in human culture since prehistoric times. Hair has been associated with youth, beauty and health, and conditions leading to hair loss prove to be a cause of immense psychological distress. Intake of food supplements and nutraceuticals including vitamins, minerals, omega fatty acids and antioxidants have been reported to play a vital role in appropriate hair follicle production as well as in immune cell function. Oxidative stress is one of the important components that plays a function in the ageing as well diminution of the hair follicle. ROS are formed by a large array of endogenous and environmental sources. The body endogenously generates defensive mechanisms, such as antioxidative enzymes and non-enzymatic antioxidative chemicals, which protect against free radicals by lowering their concentration and neutralizing them. On one side the production of free radicals escalates with age and on the other side the endogenous defense mechanisms are reduced. This imbalance causes a steady degradation of cellular and molecular structures, most definitely culminating in the ageing phenotype. The therapeutic utility of antioxidants in the treatment of androgenic alopecia has been proven scientifically and expanded in the recent years. This review presents the new approaches for prevention of oxidative stress-based alopecia.



The authors are thankful to the University Institute of Pharmacy, Pandit Ravishankar Shukla University, Raipur for the infrastructural facilities. The authors extend special thanks to the Librarian, Pt. Sundarlal Sharma Library of the University for e-resources available through UGC-INFLIBNET. This work was supported by Pt. Ravishankar Shukla University Research Scholarship [797/Fin./Sch./ 2021].



Abdel Fattah, N. S. A., Ebrahim, A. A., & El Okda, E. S. (2011). Lipid peroxidation/antioxidant activity in patients with alopecia areata. Journal of the European Academy of Dermatology and Venereology, 25(4), 403-408.

 Akar, A., Arca, E., Erbil, H., Akay, C., Sayal, A., & Gür, A. R. (2002). Antioxidant enzymes and lipid peroxidation in the scalp of patients with alopecia areata. Journal of dermatological science, 29(2), 85-90.

Almohanna, H. M., Ahmed, A. A., Tsatalis, J. P., & Tosti, A. (2019). The role of vitamins and minerals in hair loss: a review. Dermatology and therapy, 9(1), 51-70.

Arck, P. C., Overall, R., Spatz, K., Liezman, C., Handjiski, B., Klapp, B. F., Birch-Machin, M.A., Peters, E.M.J., Arck, P.C., Overall, R. & Spatz, K., (2006). Towards a “free radical theory of graying”: melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage. The FASEB Journal, 20(9), 1567-1569.

Bhandaru, M., Pasham, V., Yang, W., Bobbala, D., Rotte, A., & Lang, F. (2012). Effect of azathioprine on Na+/H+ exchanger activity in dendritic cells. Cellular Physiology and Biochemistry, 29(3-4), 533-542.

Bhise, K., Kashaw, S. K., Sau, S., & Iyer, A. K. (2017). Nanostructured lipid carriers employing polyphenols as promising anticancer agents: Quality by design (QbD) approach. International journal of pharmaceutics, 526(1-2), 506-515.

Bilandi, A., & Kataria, M. K. (2017). Minoxidil emulgel for androgenic alopecia: a literature review including patents. International Journal of Pharmaceutics and Drug Analysis, 49-58.

Cappetta, D., De Angelis, A., Sapio, L., Prezioso, L., Illiano, M., Quaini, F., Rossi, F., Berrino, L., Naviglio, S., & Urbanek, K. (2017). Oxidative stress and cellular response to doxorubicin: a common factor in the complex milieu of anthracycline cardiotoxicity. Oxidative medicine and cellular longevity, 2017.

Chen, H. W., Chien, C. T., Yu, S. L., Lee, Y. T., & Chen, W. J. (2002). Cyclosporine A regulate oxidative stress‐induced apoptosis in cardiomyocytes: mechanisms via ROS generation, iNOS and Hsp70. British Journal of Pharmacology, 137(6), 771-781.

Collin, C., Gautier, B., Gaillard, O., Hallegot, P., Chabane, S., Bastien, P., Peyron, M., Bouleau, M., Thibaut, S., Pruche, F., & Duranton, A. (2006). Protective effects of taurine on human hair follicle grown in vitro 1. International journal of cosmetic science, 28(4), 289-298.

Couto, D., Ribeiro, D., Freitas, M., Gomes, A., Lima, J. L., & Fernandes, E. (2010). Scavenging of reactive oxygen and nitrogen species by the prodrug sulfasalazine and its metabolites 5-aminosalicylic acid and sulfapyridine. Redox Report, 15(6), 259-267.

D’Agostini, F., Fiallo, P., Pennisi, T. M., & De Flora, S. (2007). Chemoprevention of smoke-induced alopecia in mice by oral administration of L-cystine and vitamin B6. Journal of dermatological science, 46(3), 189-198.

Deavall, D. G., Martin, E. A., Horner, J. M., & Roberts, R. (2012). Drug-induced oxidative stress and toxicity. Journal of toxicology, 2012.

Devasagayam, T. P. A., Tilak, J. C., Boloor, K. K., Sane, K. S., Ghaskadbi, S. S., & Lele, R. D. (2004). Free radicals and antioxidants in human health: current status and future prospects. Japi, 52(794804), 4.

Driskell, R. R., Lichtenberger, B. M., Hoste, E., Kretzschmar, K., Simons, B. D., Charalambous, M., Ferron, S.R., Herault, Y., Pavlovic, G., Ferguson-Smith, A.C., & Watt, F. M. (2013). Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature, 504(7479), 277-281.

Elelaimy, I. A., Elfiky, S. A., Hassan, A. M., Ibrahim, H. M., & Elsayad, R. I. (2012). Genotoxicity of anticancer drug Azathioprine (Imuran): role of Omega-3 (?-3) oil as protective agent. Journal of Applied Pharmaceutical Science, (Issue), 14-23.

Fehsel, K., Loeffler, S., Krieger, K., Henning, U., Agelink, M., Kolb-Bachofen, V., & Klimke, A. (2005). Clozapine induces oxidative stress and proapoptotic gene expression in neutrophils of schizophrenic patients. Journal of clinical psychopharmacology, 25(5), 419-426.

Fernández, E., Martínez-Teipel, B., Armengol, R., Barba, C., & Coderch, L. (2012). Efficacy of antioxidants in human hair. Journal of Photochemistry and Photobiology B: Biology, 117, 146-156.

Finner, A. M. (2013). Nutrition and hair: deficiencies and supplements. Dermatologic clinics, 31(1), 167-172.

Galbraith, H. Fundamental hair follicle biology and fine fibre production in animals. Animal 2010; 4 (9): 1490–509.

Gao, W., & Dalton, J. T. (2007). Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs). Drug discovery today, 12(5-6), 241-248.

Garg, N. K., Sharma, G., Singh, B., Nirbhavane, P., Tyagi, R. K., Shukla, R., & Katare, O. P. (2017). Quality by Design (QbD)-enabled development of aceclofenac loaded-nano structured lipid carriers (NLCs): An improved dermatokinetic profile for inflammatory disorder (s). International Journal of pharmaceutics, 517(1-2), 413-431.

Gilhar, A., Schrum, A. G., Etzioni, A., Waldmann, H., & Paus, R. (2016). Alopecia areata: animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies. Autoimmunity reviews, 15(7), 726-735.

Guo, E. L., & Katta, R. (2017). Diet and hair loss: effects of nutrient deficiency and supplement use. Dermatology practical & conceptual, 7(1), 1.

Guo, H., Gao, W. V., Endo, H., & McElwee, K. J. (2017). Experimental and early investigational drugs for androgenetic alopecia. Expert Opinion on Investigational Drugs, 26(8), 917-932.

Harman, D. (2002). Aging: a theory based on free radical and radiation chemistry. Science of Aging Knowledge Environment, 2002(37), cp14-cp14.

Haslam, I. S., Jadkauskaite, L., Szabó, I. L., Staege, S., Hesebeck-Brinckmann, J., Jenkins, G., Bhogal, R.K., Lim, F.L., Farjo, N., Farjo, B., & Bíró, T. (2017). Oxidative damage control in a human (mini-) organ: Nrf2 activation protects against oxidative stress-induced hair growth inhibition. Journal of Investigative Dermatology, 137(2), 295-304.

Hatem, S., Nasr, M., Moftah, N. H., Ragai, M. H., Geneidi, A. S., & Elkheshen, S. A. (2018). Melatonin vitamin C-based nanovesicles for treatment of androgenic alopecia: design, characterization and clinical appraisal. European Journal of Pharmaceutical Sciences, 122, 246-253.Held, Paul. 2015. “An Introduction to Reactive Oxygen Species Measurement of ROS in Yeast Cells.” BioTek Instruments. TechNote, 121.

Heyland, D. K., Dhaliwal, R., Suchner, U., & Berger, M. M. (2005). Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive care medicine, 31(3), 327-337.

Hu, X., Zhou, H., Zhang, D., Yang, S., Qian, L., Wu, H. M., Chen, P.S., Wilson, B., Gao, H.M., Lu, R.B., & Hong, J. S. (2012). Clozapine protects dopaminergic neurons from inflammation-induced damage by inhibiting microglial overactivation. Journal of Neuroimmune Pharmacology, 7(1), 187-201.

Huang, W. Y., Huang, Y. C., Huang, K. S., Chan, C. C., Chiu, H. Y., Tsai, R. Y., Chan, J.Y., & Lin, S. J. (2017). Stress-induced premature senescence of dermal papilla cells compromises hair follicle epithelial-mesenchymal interaction. Journal of dermatological science, 86(2), 114-122.

Hunt, N., & McHale, S. (2005). The psychological impact of alopecia. Bmj, 331(7522), 951-953.

Islam, N., Leung, P. S., Huntley, A. C., & Gershwin, M. E. (2015). The autoimmune basis of alopecia areata: a comprehensive review. Autoimmunity reviews, 14(2), 81-89.

Kaufman, K. D., Olsen, E. A., Whiting, D., Savin, R., DeVillez, R., Bergfeld, W., Price, V.H., Van Neste, D., Roberts, J.L., Hordinsky, M., & Shapiro, J. (1998). Finasteride in the treatment of men with androgenetic alopecia. Journal of the American Academy of Dermatology, 39(4), 578-589.

Kaushik, R., Gupta, D., & Yadav, R. (2011). Alopecia: herbal remedies. International Journal of Pharmaceutical Sciences and Research, 2(7), 1631.

Kil, M. S., Kim, C. W., & Kim, S. S. (2013). Analysis of serum zinc and copper concentrations in hair loss. Annals of Dermatology, 25(4), 405-409.

Kim, J. Y., Cho, H. J., Sir, J. J., Kim, B. K., Hur, J., Youn, S. W., Yang, H.M., Jun, S.I., Park, K.W., Hwang, S.J., & Kwon, Y.W. (2009). Sulfasalazine induces haem oxygenase-1 via ROS-dependent Nrf2 signalling, leading to control of neointimal hyperplasia. Cardiovascular Research, 82(3), 550-560.

Kim, S. Y., Kim, S. J., Kim, B. J., Rah, S. Y., Chung, S. M., Im, M. J., & Kim, U. H. (2006). Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+ increase are reciprocally modulated in rat cardiomyocytes. Experimental & molecular medicine, 38(5), 535-545.

Koca, R., Armutcu, F., Altinyazar, C., & Gürel, A. (2005). Evaluation of lipid peroxidation, oxidant/antioxidant status, and serum nitric oxide levels in alopecia areata. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 11(6), CR296-299.

Kumar, P., Singh, S. K., Handa, V., & Kathuria, H. (2018). Oleic acid nanovesicles of minoxidil for enhanced follicular delivery. Medicines, 5(3), 103.

Labrozzi, A. (2020). Nutrients in hair supplements: evaluation of their function in hair loss treatment. Hair Ther Transplant, 10(1), 1-6.

López‐Ongil, S., Hernández‐Perera, O., Navarro‐Antolín, J., Perez de Lema, G., Rodríguez‐Puyol, M., Lamas, S., & Rodríguez‐Puyol, D. (1998). Role of reactive oxygen species in the signalling cascade of cyclosporine A‐mediated up‐regulation of eNOS in vascular endothelial cells. British journal of pharmacology, 124(3), 447-454.


Mantel, A., McDonald, J. T., Goldsborough, K., Harvey, V. M., & Chan, J. (2017, October). Prostaglandin D2 uses components of ROS signaling to enhance testosterone production in keratinocytes. In Journal of Investigative Dermatology Symposium Proceedings (Vol. 18, No. 2, pp. S81-S84). Elsevier.

Maxson & Mitchell. 2016. “肌肉作内分泌和旁分泌器官 HHS Public Access.” Physiology & Behavior 176 (1): 139–48.

McElwee, K. J., & Shapiro, J. S. (2012). Promising therapies for treating and/or preventing androgenic alopecia. Skin therapy letter, 17(6), 1-4.

Najah, R. H., Mohammad, A. A. H., & Ammar, R. M. R. (2008). Effect of atorvastatin on oxidative stress parameters and lipid profile in type 2 diabetic patients. IIUM Medical Journal Malaysia, 7(2).

Ogun, A. O. (2015). Biochemistry of Reactive Oxygen and Nitrogen Species, Basic Principles and Clinical Significance of Oxidative Stress.

Padayatty, S. J., Katz, A., Wang, Y., Eck, P., Kwon, O., Lee, J. H., Chen, S., Corpe, C., Dutta, A., Dutta, S.K., & Levine, M. (2003). Vitamin C as an antioxidant: evaluation of its role in disease prevention. Journal of the American college of Nutrition, 22(1), 18-35.

Park, S. H., Sung, J. H., Kim, E. J., & Chung, N. (2014). Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines. Brazilian journal of medical and biological research, 48, 111-119.

Perez de Hornedo, J., De Arriba, G., Calvino, M., Benito, S., & Parra, T. (2007). Cyclosporin A causes oxidative stress and mitochondrial dysfunction in renal tubular cells. Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia, 27(5), 565-573.

Price, V. H., & Colombe, B. W. (1996). Heritable factors distinguish two types of alopecia areata. Dermatologic clinics, 14(4), 679-689.

Prie, B. E., Iosif, L., Tivig, I., Stoian, I., & Giurcaneanu, C. (2016). Oxidative stress in androgenetic alopecia. Journal of medicine and life, 9(1), 79.

Radimer, K., Bindewald, B., Hughes, J., Ervin, B., Swanson, C., & Picciano, F. M. (2000). Dietary supplement use by us adults: Data from the National Health and Nutrition Examination Survey. Am. J. Epidemiol, 160(4).

Rajput, R., (2017). The Concept of Cyclical Nutritional Therapy for Hair Growth Which Can Be Applied for Wellness. Journal of Nutrition & Food Sciences 07 (04).

Ramezani, V., Honarvar, M., Seyedabadi, M., Karimollah, A., Ranjbar, A. M., & Hashemi, M. (2018). Formulation and optimization of transfersome containing minoxidil and caffeine. Journal of Drug Delivery Science and Technology, 44, 129-135.

Ramkar, S., Sah, A. K., Bhuwane, N., Choudhary, I., Hemnani, N., & Suresh, P. K. (2020). Nano-lipidic carriers as a tool for drug targeting to the pilosebaceous units. Current Pharmaceutical Design, 26(27), 3251-3268.

Ramkar, S., & Suresh, P. K. (2022). Finasteride-loaded nano-lipidic carriers for follicular drug delivery: preformulation screening and Box-Behnken experimental design for optimization of variables. Heliyon, 8(8), e10175.

Richter, K., Konzack, A., Pihlajaniemi, T., Heljasvaara, R., & Kietzmann, T. (2015). Redox-fibrosis: Impact of TGFβ1 on ROS generators, mediators and functional consequences. Redox biology, 6, 344-352.

Rushton, D. H. (2002). Nutritional factors and hair loss. Clinical and Experimental Dermatology: Clinical dermatology, 27(5), 396-404.

Rutkowski, M., & Grzegorczyk, K. (2012). Adverse effects of antioxidative vitamins. International journal of occupational medicine and environmental health, 25(2), 105-121.

Ryter, S. W., Kim, H. P., Hoetzel, A., Park, J. W., Nakahira, K., Wang, X., & Choi, A. M. (2007). Mechanisms of cell death in oxidative stress. Antioxidants & redox signaling, 9(1), 49-89.

Sathishkumar, P., Preethi, J., Vijayan, R., Yusoff, A. R. M., Ameen, F., Suresh, S., Balagurunathan, R., & Palvannan, T. (2016). Anti-acne, anti-dandruff and anti-breast cancer efficacy of green synthesised silver nanoparticles using Coriandrum sativum leaf extract. Journal of Photochemistry and Photobiology B: Biology, 163, 69-76.

Schiffer, L., Arlt, W., & Storbeck, K. H. (2018). Intracrine androgen biosynthesis, metabolism and action revisited. Molecular and Cellular Endocrinology, 465, 4-26.

Sinbad, O. O., Folorunsho, A. A., Olabisi, O. L., Ayoola, O. A., & Temitope, E. J. (2019). Vitamins as antioxidants. Journal of Food Science and Nutrition Research, 2(3), 214-235.

Snezhkina, A. V., Kudryavtseva, A. V., Kardymon, O. L., Savvateeva, M. V., Melnikova, N. V., Krasnov, G. S., & Dmitriev, A. A. (2019). ROS generation and antioxidant defense systems in normal and malignant cells. Oxidative medicine and cellular longevity, 2019.

Sheikh, S., Ahmad, A., Ali, S. M., Ahmad, M. U., Paithankar, M., Saptarshi, D., ... & Ahmad, I. (2015). A new topical formulation of minoxidil and finasteride improves hair growth in men with androgenetic alopecia. Journal of Clinical & Experimental Dermatology Research, 6(1), 1-6.

Suresh, P. K., Sah, A. K., & Daharwal, S. J. (2014). Role of free radicals in ocular diseases: An overview. Research J. Pharm. and Tech, 7(11), 1330-1344.

Suresh, P. K., & Sah, A. K. (2013). Free radicals: generation, defense and implications in various diseases. Research Journal of Pharmaceutical, Biological and Chemical Sciences, 4, 247-269.

Thiboutot, D., Gilliland, K., Cong, Z., Jabara, S., McAllister, J. M., Sivarajah, A., & Clawson, G. (2003). Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1). Journal of Investigative Dermatology, 120(6), 905-914.

Timbo, B. B., Ross, M. P., McCarthy, P. V., & Lin, C. T. J. (2006). Dietary supplements in a national survey: prevalence of use and reports of adverse events. Journal of the American Dietetic Association, 106(12), 1966-1974.

Tinggi, U. (2008). Selenium: its role as antioxidant in human health. Environmental health and preventive medicine, 13(2), 102-108.

Trüeb, R. M. (2009). Oxidative stress in ageing of hair. International journal of trichology, 1(1), 6.

Upton, J. H., Hannen, R. F., Bahta, A. W., Farjo, N., Farjo, B., & Philpott, M. P. (2015). Oxidative stress–associated senescence in dermal papilla cells of men with androgenetic alopecia. Journal of Investigative Dermatology, 135(5), 1244-1252.

Wagener, F. A., Carels, C. E., & Lundvig, D. M. (2013). Targeting the redox balance in inflammatory skin conditions. International journal of molecular sciences, 14(5), 9126-9167.

Wassmann, S., Laufs, U., Müller, K., Konkol, C., Ahlbory, K., Bäumer, A. T., Linz, W., Böhm, M., & Nickenig, G. (2002). Cellular antioxidant effects of atorvastatin in vitro and in vivo. Arteriosclerosis, thrombosis, and vascular biology, 22(2), 300-305.

Wolf, R., Schönfelder, G., Paul, M., & Blume-Peytavi, U. (2003). Nitric oxide in the human hair follicle: constitutive and dihydrotestosterone-induced nitric oxide synthase expression and NO production in dermal papilla cells. Journal of molecular medicine, 81(2), 110-117.

Yadav, A., Kumari, R., Yadav, A., Mishra, J. P., Srivatva, S., & Prabha, S. (2016). Antioxidants and its functions in human body-A Review. Res. Environ. Life Sci, 9(11), 1328-1331.

Yasuko, Shindo, Witt Eric, Derick Han, and William Epstein. 1994. “shindo1994.pdf.” The Society for Investigative Dermatology 102: 122–24.

 Yu, M., Finner, A., Shapiro, J., Lo, B., Barekatain, A., & McElwee, K. J. (2006). Hair follicles and their role in skin health. Expert Review of Dermatology, 1(6), 855-871.


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