comparative study on the effect of retinoic acid, glycolic acid and salicylic acid

8/10/2019 Comparative Study on the Effect of Retinoic Acid, Glycolic Acid and Salicylic Acid

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Egypt. J. Histol. Vol. 32, No. 1, June, 2009: 17 - 32

Comparative Study on the Effect of Retinoic Acid, Glycolic Acid andSalicylic Acid on the Thin Skin of Adult Female Guinea Pig. Light and

Electron Microscopic StudyAbeer A. Abd El Samad and Nagwa Kostandy Kalleny

Histology Department, Faculty of Medicine, Ain Shams University

ABSTRACT

Introduction:Many products had been used as chemical peeling agents to renew thin skin. Retinoic, Glycolic and

Salicylic acids were used in many dermatological diseases with hyperkeratinization and/or hyperpigmentation.

Aim of the Work: To evaluate and compare the effects of these acids on the thin skin of adult female guinea pig.

Materials and Methods:Twenty animals were used and were divided into four equal groups. Group I served as the

control group, whereas the other treated groups were topically applicated daily on shaved area of back skin with

Retinoic (0.05%), Glycolic (12%) and Salicylic (10%) acids in Groups II, III and IV, respectively. Thin skin specimens

were processed for light and transmission electron microscopic studies. Morphometric and statistical studies weredone.

Results:Groups II, III and IV showed high significant increase in mean thickness of epidermal nucleated keratinocytes as

compared to Control group. Group II showed proliferation hyperkeratosis and acanthosis and shrinkage of the sebaceous

glands with decreased sebum production. Group III showed skin peeling by removing superficial layers of epidermis,

cytoplasmic and nuclear degeneration with disruption of intercellular junctions and degeneration in melanocytes with

marked decrease of melanin. Both Retinoic and Glycolic acids apparently increased the production of collagen and

elastic fibers as compared to control. Group IV showed skin peeling mainly by direct action on intercellular cement

substance and partially by inducing proliferation hyperkertosis.

Conclusion:Both Retinoic and Glycolic acids showed complementary actions in treatment of hyperpigmentation and

as chemical peeling agents. Salicylic acid also is a peeling agent, but its effects could be covered by either Retinoic or

Glycolic acids.

Recommendation:It is recommended to use combination of both Retinoic and Glycolic acids to give better effects on

various skin disorders with hyperkeratinization and hyperpigmentation.

Original Article

Key Words: Retinoic acid, glycolic acid, salicylic acid,skin, guinea Pig.

Corresponding Author:Abeer A. Abd El SamadTel.:0105223262 E-mail:[email protected]

(ISSN: 1110 - 0559)

3 (1128-2009)

INTRODUCTION

Hyperkeratinization is a fundamental event in a

majority of skin disorders. Hyperkeratinization is usually

the result of decreased desquamation due to increased

corneocyte cohesion. Agents that control or modifykeratinization can be useful in treatment of many skin

disorders1.

New methods to protect skin from sun exposure

are necessary if we need to overcome skin cancer and

photoaging. Sunscreens are useful, but their protection is

not ideal because of inadequate use, incomplete spectral

protection and toxicity2. Superficial chemical peeling

has become increasingly a popular method for facial

renewal3.

Some authors4 stated that photoaging

pathophysiology is characterized clinically by wrinkles,

mottled pigmentation, rough skin and loss of skin tone

with histologic changes in the dermal connective tissue.Other authors5 stated that the use of topical retinoids

were capable of repairing photoaged skin and treating

intrinsically aged skin. Moreover, some investigators6

noticed that topical retinoids were considered the first-

line therapy in the treatment of acne vulgaris. Isotretinoin

(retinoids) appeared to be the most potent agent that

affects all the pathogenic features of acne, which resulted

from the interplay of 4 factors: Increased production of

sebum by the sebaceous gland, altered keratinization of

follicular keratinocytes, activity of Propionibacterium


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Comparative Study on the Effect of Retinoic Acid, Glycolic Acid and Salicylic Acid on the Thin Skin

18

acnes (P. acnes) and inflammation by P. acnes7. These

pathological effects of acne are not life threatening, but

it had significant physical and psychosocial morbidity8.

Acne is the most prevalent skin condition encountered

by dermatologists, affecting nearly 85% of the people

between the ages of 12 and 24 years9. In addition, some

authors10noted that retinoic acid and glycolic acid were

frequently used in the treatment of acne and skin aging,

as well as improving skin healing after dermabrasion andin photoaged skin.

Alpha hydroxy acids (AHA), a group of naturally-

occurring compounds, have the potential to improve

a variety of skin disorders11. Some authors12stated that

AHAs are derived from food sources; although many of

these compounds are available, glycolic acid has been the

most widely used. Hydroxy acids had been extensively

used in cosmetic and dermatologic formulations because

of their satisfactory results in terms of maintaining a

young and healthy skin and in recovering aged skin13.

Moreover, some authors14 stated that Glycolicacid, an alpha-hydroxy acid derived from fruit and

milk sugars, had been commonly used as a cosmetic

ingredient since it was known to have photo-protective,

anti-inflammatory effects and anti-oxidant effect in

UV-irradiated skin. Similarly, other authors15noted that

Glycolic acid was widely used as an agent for chemical

peeling and contributed to the recovery of photodamaged

skin through various actions.

Some scientists16reported that chemical peeling with

salicylic acid was an effective method for the renewal of

photo-damaged skin.

The aim of the present study was to evaluate and

compare the effect of Retinoic acid, Glycolic acid and

Salicylic acid on the thin skin of adult female guinea

pig.

MATERIALS AND METHODS

The current study was performed in the Medical

Research Center, Faculty of Medicine, Ain Shams

University. Twenty adult female guinea pigs were used,

with an average weight of 300 grams each. Animals

were fed on standard laboratory guinea pig diet with freeaccess to water. All animals were prepared by shaving the

hair over their back with a surface area measuring 2.5 x

2.5 cm. They were divided into the following four groups

(five animals each):

Group I (Control Group):Consisted of 5 untreated

guinea pigs.

Group II (Retinoic acid Group): Retinoic acid

cream (0.05%) was topically applied daily on the shaved

area, just to cover it, for three weeks. It was manufactured

by Cilag A.G. as Retin-A.

Group III (Glycolic acid Group): Glycolic acid

cream (12%) was topically applied daily on the shaved

area, just to cover it, for three weeks. It was manufactured

by ISIS Pharma as Glyco-A.

Group IV (Salicylic acid Group): Salicylic acid

ointment (10%) was topically applied daily on the

shaved area, just to cover it, for three weeks. It was

manufactured by a pharmacy. The Salicylic acid wasprepared in Vaseline base (vehicle), in which Salicylic

powder was added to equivalent amount of paraffin oil

and mixed well to form homogenous paste, then vaseline

was added gradually to get homogenous ointment. This

preparation is the lipophylic preparation, to be absorbed

through skin and it is the active form in contrast to the

aqueous formula.

All animals were sacrificed by decapitation under

anesthesia by Thiopental Sodium. The shaved areas

of skin of all animals were dissected out, then cut by

sharp surgical blade into slices and were prepared then

subjected to light and transmission electron microscopicstudies.

For light microscopic study (LM):1. Formalin (10%)

fixed skin slices were processed to form paraffin

blocks. Serial sections 5m in thickness were

prepared and subjected to Haematoxylin and Eosin

stain (H&E) and Orcein stain17.

For transmission electron microscopic study2.

(TEM): Phosphate buffered gluteraldehyde fixed

small pieces of the thin skin were processed to form

capsules. Semi-thin sections were cut at 1m in

thickness using glass knife, stained by 1% toluidine

blue in 1% borax and examined by light microscope.

Ultra-thin sections (50-60nm in thickness) were cut

using ultra-microtome. Then sections were mounted

on copper grids and stained with saturated solution

of uranyl acetate18followed by lead citrate19. Ultra-

thin sections were examined and photographed by

JEM-1200 EXII transmission electron microscope

in Faculty of Science, Ain Shams University.

Morphometric and Statistical studies:

The thicknesses of nucleated epidermal keratinocytes(m) in 5 fields from H&E sections from each animal of

all groups were measured.

The measurements were done by using the image

analyzer (Leica Q 500 MC program) in Histology

Department, Faculty of Medicine, Ain Shams University.

Data were entered on an IBM compatible PC and statistical

analysis was done using the Statistical Package of Social

Sciences (SPSS version 11). Descriptive statistics were

done in the form of mean and standard deviation.

Mean of each group was compared with the


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Abeer A. Abd El Samad and Nagwa Kostandy Kalleny

19

others using the One Way Analysis of Variance (One

Way ANOVA) with Post hoc analysis. As regards

the probability, the least significant level used was at

P


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this group showed apparent increase in thickness of the

nucleated cells particularly in the cells of the stratum

spinosum and stratum granulosum as compared to control.

On the other hand, the stratum corneum was apparently

thinned out and peeled as noticed in H&E and toluidine

blue stained sections. The keratinocytes appeared

vacuolated and degenerated. Some keratinocytes showed

variable nuclear changes ranging from pyknosis to

karyorrhexis. The melanin was markedly decreased ascompared to control (Figs. 18,19&20).

Ultra-thin sections revealed that the melanocytes

appeared degenerated containing few melanin pigments.

Some cells of the stratum basale showed various stages

of degeneration, in which some showed vacuolization,

others appeared shrunken with deformed nuclei, whereas

others showed normal control appearance with few

melanin granules (Fig. 21). The cytoplasm of the stratum

spinosum showed marked decrease in tonofilaments

content as compared to control, with disruption of

desmosomes and intercellular disjunctions also showing

widening in the intercellular spaces. The nuclei showedchromatin pattern different than that of control with

unapparent nucleoli (Fig. 22).

The dermis showed active fibroblasts with marked

increase in the content of organized bundles of dense

collagen fibers as compared to control (Fig. 23).

Moreover, increased content of elastic fibers as compared

to control was noticed in orcein stained sections (Fig. 24).

No remarkable changes in the sebaceous glands of these

animals as compared to the control.

Group IV (Salicylic acid Group):

The epidermis of thin skin sections of animals of this

group showed apparent increased thickness of viable

keratinocytes showing areas of acanthosis, however

the thickness of the stratum corneum was decreased as

compared to the control. The cells of the stratum spinosum

showed vesicular nuclei. The melanin was dispersed in

the keratinocytes particularly those of the stratum basale

followed by the stratum spinosum (Figs. 25&26).

Ultra-thin sections revealed nearly normal and

viable cells of the stratum spinosum. They showed

apparent normal nuclear confi

guration with few melaningranules and well-defined bundles of tonofilaments in

their cytoplasm with preserved desmosomes between

cells. However, there was apparent separation between

cells due to widening in the intercellular space

(Figs. 27&28). The stratum granulosum showed

kerato-hyalin granules, whereas the stratum corneum

appeared less compact as compared to that of the control

(Fig. 29).

The content of dermal collagen fibers showed nearly

no remarkable difference as compared to control. In

addition, nearly no remarkable difference in content of

0

20

40

60

80

100

120

140

160

180

Group I

Control

Group II

Retinoic

acid

Group III

Glycolic

acid

Group IV

Salicylic

acid

Histogram 1: Showing the mean thickness of nucleated epidermal

keratinocytes in different studied groups.

elastic fibers in orcein stained sections as compared to

control (Fig. 30). Moreover, no remarkable changes in

the sebaceous glands of these animals as compared to the

control.

Morphometric and Statistical Results:

Table (1) and Histogram (1) showed the means

and standard deviations of thickness of epidermalkeratinocytes in different studied groups.

Table (2) showed high significant increase in mean

thickness of epidermal keratinocytes (p


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Fig. 2: A photomicrograph of a section of thin skin of female guinea pig,

showing the stratum basale of keratinocytes (B), the stratum spinosum

(S) and the stratum granulosum (G). The stratum corneum consists of

many layers of flattened non-nucleated acidophilic keratinized cells (K).

Notice the brownish melanin pigment ().Group I H&E X 640.


showing epidermis and dermis. The dermis shows sebaceous glands ()

and hair follicles ().

Group I Toluidine blue X 640.

Table 2: Showing the significance of difference in mean

thickness of nucleated epidermal keratinocytes in different

studied groups using one way ANOVA with Post hoc analysis:

(I) code (J) codeMean Difference

(I-J)Significance

Group I

(Control)

Group II -130.02200 p


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Fig. 4: An electron-micrograph of a section of thin skin of female guinea

pig, showing melanocyte in-between cells of the stratum basale. It

shows cell process containing melanin granules (). Cells of the stratum

spinosum show euchromatic nuclei and tonofilaments in their cytoplasm

(). The dermis shows collagen fibers (C).Group I TEM X 4000.

Fig. 5: An electron-micrograph of a section of thin skin of female

guinea pig, showing keratinocytes of the stratum basale with

euchromatic nuclei. Their cytoplasm contains intermediate filaments

() and melanin granules ().

Group I TEM X 3000.


pig, showing cell of stratum spinosum with bundles of tonofilaments.

The cytoplasm of the stratum granulosum appears filled with kerato-

hyalin granules (G). Notice the desmosomes in-between cells of stratum

spinosum and stratum granulosum ().The cells of the stratum corneun

show keratin filaments embedded in an amorphous matrix.

Group I TEM X 3000.

Fig. 7: An electron-micrograph of a section of the reticular layer of

dermis thin skin of female guinea pig, showing collagen fibers (C) and

dermal fibroblasts ().

Group I TEM X 6000.


showing network of elastic fibers in the reticular layer (E) and few thinner

fibers in the papillary layer () of the dermis.

Group I Orcein X 250.


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Fig. 12: A photomicrograph of a section of thin skin of female guinea

pig, showing vesicular nuclei of stratum spinosum cells that showed

mitotic figures with prominent anaphase stage (). Notice the reduced

melanin pigmentation as compared to control.

Group II H&E X 640.


guinea pig, showing active euchromatic nuclei with extended chromatin

in stratum spinosum cells. Their cytoplasm contained tonofilaments ()

terminating in desmosomes.

Group II TEM X 3000.


pig, showing acinus of sebaceous gland. The cells of the basal layer of

the acinus appear flattened () resting on a basal lamina. The adjacent

rounded cells contain abundant fat droplets in their cytoplasm.

Group I TEM X 2000.


pig, showing cells at the central part of a sebaceous gland acinus with

shrunken and condensed nuclei and their cytoplasm appear filled with

fat droplets.

Group I TEM X 3000.


showing prominent rete pegs with apparent increased thickness of viable

keratinocytes. Whereas, the stratum corneum was markedly thinned out

as compared to control.

Group II H&E X 250.


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24


guinea pig, showing increased number of cells of the stratum granulosum

rich with large kerato-hyalin granules. Whereas the stratum corneum was

apparently thinner and more compact as compared to control.



guinea pig, showing dermal collagen fibers deposited from fibroblast.



pig, showing massive deposition of elastic fibers () in the dermis as

compared to control.

Group II Orcein X 250.


pig, showing undifferentiated cells of the peripheral part of a sebaceous

gland. However the cells at the central part of acini appeared condensed

and shrunken containing altered fat droplets as compared to control.


Fig. 18:A photomicrograph of a section of thin skin of female guinea

pig, showing apparent increase in thickness of epidermal keratinocytes

as compared to control. Notice the detached stratum corneum.

Group III H&E X 250.


showing vacuolated and degenerated keratinocytes. Notice pyknosis ()

and karyorrhexis () in some keratinocytes. The melanin was markedly

decreased as compared to control.

Group III H&E X 640.


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25


pig, showing widening in the intercellular spaces of stratum spinosum cells

with disruption of desmosomes and intercellular disjunctions (). Notice

the marked decrease in tonofilaments content as compared to control.

The nuclei showed chromatin pattern different than that of control withunapparent nucleoli.

Group III TEM X 3000.


pig, showing active fibroblasts () with marked increase in the content of

organized bundles of dense collagen fibers as compared to control.



pig, showing apparent increase in thickness of the cells of the stratum

spinosum (S) and stratum granulosum (G) as compared to control. Notice

the thinned out and peeled stratum corneum.

Group III Toluidine blue X 250.


guinea pig, showing various stages of degeneration of stratum basal

cells, in which vacuolization (V), shrunken cells with deformed nuclei

(S) appear. Whereas other cells show normal control appearance with few

melanin granules (C). Notice the degenerated melanocyte containing few

melanin pigments (M).



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26


pig, showing increased content of elastic fibers () in the dermis as

compared to control.

Group III Orcein X 250.

Fig. 25:A photomicrograph of a section of thin skin of female guinea

pig, showing apparent increase in thickness of keratinocytes, however

the stratum corneum appears thinner than that of the control.

Group IV H&E X 250.


pig, showing dispersed melanin in the keratinocytes particularly those of

the stratum basale followed by the stratum spinosum.

Group IV H&E X 640.


guinea pig, showing apparent separation between stratum spinosum cells

due to widening in the intercellular space. They show apparent normal

nuclear configuration and few melanin granules.

Group IV TEM X 4000.


pig, showing well-defined bundles of tonofilaments in their cytoplasm

with preserved desmosomes between cells of stratum spinosum.

Group IV TEM X 4000.


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DISCUSSION

The epidermis of thin skin sections of animals of

Group II showed that topical application of Retinoic acid

increased the thickness of viable keratinocytes forming

prominent rete pegs. This was proved by morphometricand statistical study where the mean thickness of

nucleated epidermal keratinocytes was high significantly

increased (p


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Topical application of Retinoic acid in animals of

Group II in the present study induced undifferentiation

in acinar cells and shrinkage in the sebaceous glands

with altered and reduced content of sebum as compared

to control, explained as hypo-activity in the sebaceous

gland. In addition, the nuclei of the sebocytes appeared

shrunken and condensed. This was in agreement with

some scientists27 who stated that isotretinoin (retinoic

acid) is the most effective drug in reducing sebaceousgland size (up to 90%) by decreasing proliferation of basal

sebocytes, suppressing sebum production and inhibiting

sebocyte differentiation in vivo. The molecular basis for

its anti-sebotrophic activity had not been fully elucidated.

Isotretinoin also exhibited anti-inflammatory activities.

Systemic isotretinoin is considered to be the regimen of

choice in severe seborrhoea, since it reduced sebocyte

lipid synthesis by 75%. Moreover, other scientists28

clarified that isoterinoin induced apoptosis in sebocytes in

addition to inhibiting cell-cycle progression and reduced

sebaceous lipid production. Coinciding, some scientists29

noticed that isotretinoin is the only therapeutic agent that

drastically reduced the size and secretion of sebaceousglands and it is the most potent agent available for

treatment of acne by inducing apoptosis in the cells of

the sebaceous glands. The ability of isotretinoin to induce

apoptosis is specific and selective to sebocytes, but not

keratinocytes; nor dermal fibroblasts30. This coincided

with the results of Group II of the present study, in which

the keratinocytes exhibited euchromatic active nuclei

and the dermal fibroblasts showed active synthesis of

collagen.

Topical application of Glycolic acid in group III in the

present study, showed a high significant decrease in mean

thickness of nucleated epidermal keratinocytes (p


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group III in this study did not show remarkable changes

in the sebaceous glands as compared to the control.

Coinciding, some investigators36 noticed that glycolic

acid did not affect sebum secretion of the facial skins

of patients with facial acne however glycolic acid was a

popular superficial chemical peel agent for the treatment

of facial acne and increased sebum secretion which is

one of the major aetiological factors of acne.

Some scientists37 clarified that alpha-hydroxy acid

(AHA) peels had been recognized as important adjunctive

therapy in a variety of conditions including photodamage,

melasma, hyper-pigmentation disorders and acne. It had

been demonstrated that AHAs improve these disorders by

thinning the stratum corneum, promoting epidermolysis,

dispersing basal layer melanin and increasing collagen

synthesis within the dermis. These effects coincided

with the peeling and thinning of the stratum corneum,

in addition to the marked decrease of melanin with

degeneration of the melanocytes and increase in collagen

fibers in group III of the present study.

The epidermis of thin skin sections of animals that

received topical application of Salicylic acid (Group IV)

in the present study showed apparent decrease thickness

of the stratum corneum as compared to the control. In

addition, high significant decrease in mean thickness of

nucleated epidermal keratinocytes (p


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acid did not show dermal fibroblastic stimulation.

It is recommended to apply topical combination

of both Retinoic and Glycolic acids as they showed

complementary actions as chemical peeling agents and

in the treatment of acne, however Salicylic acid better

not to be used as a peeling agent and in treatment of acne,

mostly because its effects could be covered by either

Retinoic or Glycolic acids and also because of its knownsystemic side effects.

REFERENCES

Van Scott EJ and Yu RJ. (1984):1. Hyperkeratinization,

corneocyte cohesion and alpha hydroxy acids. J.Am.Acad.

Dermatol. Nov;11(5 Pt 1):867-879.

Pinnell SR. (2003):2. Cutaneous photodamage, oxidative stress

and topical antioxidant protection. J. Am. Acad. Dermatol.

Jan; 48(1):1-19; quiz 20-22.

Song JY, Kang HA, Kim MY, Park YM and Kim HO. (2004):3.

Damage and recovery of skin barrier function after glycolic acid

chemical peeling and crystal microdermabrasion. Dermatol. Surg.

Mar;30(3):390-394.

Kang S, Fisher GJ and Voorhees JJ. (2001):4. Photoaging:

Pathogenesis, prevention and treatment. Clin. Geriatr. Med.

Nov;17(4):643-59, v-vi.

Singh M and Griffiths CE. (2006):5. The use of retinoids in the

treatment of photoaging. Dermatol.Ther. Sep-Oct;19(5):297-305.

Berger R, Rizer R, Barba A, Wilson D, Stewart D, Grossman6.

R, Nighland M and Weiss J. (2007):Tretinoin gel microspheres

0.04% versus 0.1% in adolescents and adults with mild to

moderate acne vulgaris: A 12-week, multicenter, randomized,

double -blind, parallel-group, phase IV trial. Clin. Ther.

Jun; 29(6):1086-1097.

Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S,7.

Legaspi AJ, Brightbill HD, Holland D, Cunliffe WJ, Akira S,

Sieling PA, Godowski PJ and Modlin RL. (2002): Activation

of toll-like receptor 2 in acne triggers inflammatory cytokine

responses. J.Immunol. Aug 1;169(3):1535-1541.

Bickers DR, Lim HW, Margolis D, Weinstock MA,8.

Goodman C, Faulkner E, Gould C, Gemmen E and Dall

T. (2006):The burden of skin diseases: 2004 a joint project of

the American Academy of Dermatology Association and the

Society for Investigative Dermatology. J. Am. Acad. Dermatol.

Sep;55(3):490-500.

White GM. (1998):9. Recent findings in the epidemiologic

evidence, classifi

cation and subtypes of acne vulgaris. J. Am.Acad.Dermatol. Aug;39(2 Pt 3):S34-S37.

Landecker A, Katayama ML, Mammana AK, Leitao RM,10.

Sachetta T, Gemperli R and Neves RI. (2001):Effects of retinoic

and glycolic acids on neoangiogenesis and necrosis of axial dorsal

skin flaps in rats. Aesthetic Plast.Surg. Mar-Apr;25(2):134-139.

Sexton CR and Rubin MG. (1994):11. An overview of alpha

hydroxy acids. Dermatol.Nurs. Feb;6(1):17-22, 74; quiz 23.

Inan S, Oztukcan S, Vatansever S, Ermertcan AT, Zeybek D,12.

Oksal A, Giray G and Muftuoglu S. (2006): Histopathological

and ultrastructural effects of glycolic acid on rat skin. Acta

Histochem. ;108(1):37-47.

Rodrigues LH and Maia Campos PM. (2002):13. Comparative

study of the effects of cosmetic formulations with or without

hydroxy acids on hairless mouse epidermis by histopathologic,

morphometric and stereologic evaluation. J. Cosmet. Sci.

Sep-Oct;53(5):269-282.

Ahn KS, Park KS, Jung KM, Jung HK, Lee SH, Chung SY,14.

Yang KH, Yun YP, Pyo HB, Park YK, Yun YW, Kim DJ, Park

SM and Hong JT. (2002): Inhibitory effect of glycolic acid on

ultraviolet B-induced c-fos expression, AP-1 activation and p53-

p21 response in a human keratinocyte cell line. Cancer Lett.Dec 5;186(2):125-135.

Okano Y, Abe Y, Masaki H, Santhanam U, Ichihashi M and15.

Funasaka Y. (2003):Biological effects of glycolic acid on dermal

matrix metabolism mediated by dermal fibroblasts and epidermal

keratinocytes. Exp.Dermatol. ;12 Suppl 2:57-63.

Dainichi T, Ueda S, Furue M and Hashimoto T. (2008):16. By the

grace of peeling: The brace function of the stratum corneum in the

protection from photo-induced keratinocyte carcinogenesis. Arch.

Dermatol.Res. Apr; 300 Suppl 1:S31-S38.

Bancroft JD and Cook HC. (1994):17. Manual of Histological

Techniques and their Diagnostic Application. Churchill

Livingstone, Longman Group UK limited: 27&57

WATSON ML. (1958):18. Staining of tissue sections for electron

microscopy with heavy metals. J. Biophys. Biochem.Cytol.

Jul 25;4(4):475-478.

Reynolds ES. (1963):19. The use of lead citrate at high pH

as an electron-opaque stain in electron microscopy. J. Cell.

Biol. ;17(1):208-212.

Gilchrest BA. (1996):20. A review of skin ageing and its medical

therapy. Br.J.Dermatol. Dec;135(6):867-875.

Pierard GE, Kligman AM, Stoudemayer T and Leveque JL.21.

(1999): Comparative effects of retinoic acid, glycolic acid and a

lipophilic derivative of salicylic acid on photodamaged epidermis.

Dermatology; 199(1):50-53.

Voorhees JJ. (1990):22. Clinical effects of long-term therapy with

topical tretinoin and cellular mode of action. J. Int. Med. Res. ;18

Suppl 3:26C-28C.

Schroeder M and Zouboulis CC. (2007):23. All-trans-retinoic acid

and 13-cis-retinoic acid: Pharmacokinetics and biological activity

in different cell culture models of human keratinocytes. Horm.

Metab.Res. Feb;39(2):136-140.

Popp C, Kligman AM and Stoudemayer TJ. (1995):24.

Pretreatment of photoaged forearm skin with topical tretinoin

accelerates healing of full-thickness wounds. Br.J.Dermatol.

Jan;132(1):46-53.

Kang S. (2005):25. The mechanism of action of topical retinoids.

Cutis Feb;75(2 Suppl):10-3; discussion 13.

Kafi

R, Kwak HS, Schumacher WE, Cho S, Hanft VN,26.Hamilton TA, King AL, Neal JD, Varani J, Fisher GJ, Voorhees

JJ and Kang S. (2007):Improvement of naturally aged skin with

vitamin A (retinol). Arch. Dermatol. May;143(5):606-612.

Orfanos CE and Zouboulis CC. (1998):27. Oral retinoids in the

treatment of seborrhoea and acne. Dermatology ;196(1):140-147.

Nelson AM, Gilliland KL, Cong Z and Thiboutot DM.28.

(2006): 13-cis Retinoic acid induces apoptosis and cell

cycle arrest in human SEB-1 sebocytes. J. Invest. Dermatol.

Oct;126(10):2178-2189.

Nelson AM, Zhao W, Gilliland KL, Zaenglein AL, Liu29.

W and Thiboutot DM. (2008): Neutrophil gelatinase-

associated lipocalin mediates 13-cis retinoic acid-induced


15/16


31

apoptosis of human sebaceous gland cells. J. Clin. Invest.

Apr;118(4):1468-1478.

Ulukaya E, Kurt A and Wood EJ. (2001):30. 4-(N-hydroxyphenyl)

retinamide can selectively induce apoptosis in human epidermoid

carcinoma cells but not in normal dermal fibroblasts. Cancer

Invest. ;19(2):145-154.

Hood HL, Kraeling ME, Robl MG and Bronaugh RL.31.

(1999): The effects of an alpha hydroxy acid (glycolic acid)

on hairless guinea pig skin permeability. Food Chem.Toxicol.Nov;37(11):1105-1111.

Rubino C, Farace F, Dessy LA, Sanna MP and Mazzarello32.

V. (2005): A prospective study of anti-aging topical therapies

using a quantitative method of assessment. Plast. Reconstr. Surg.

Apr;115(4):1156-62; discussion 1163-1164.

Slavin JW. (1998):33. Considerations in alpha hydroxy acid peels.

Clin. Plast. Surg. Jan;25(1):45-52.

Wang X. (1999):34. A theory for the mechanism of action of the

alpha-hydroxy acids applied to the skin. Med. Hypotheses

Nov;53(5):380-382.

Saint Lger D, Lvque JL and Verschoore M. (2007):35. The use

of hydroxy acids on the skin: Characteristics of C8-lipohydroxy

acid. J. Cosmet. Dermatol. Mar;6(1):59-65.

Lee SH, Huh CH, Park KC and Youn SW. (2006):36. Effects

of repetitive superficial chemical peels on facial sebum

secretion in acne patients. J. Eur. Acad. Dermatol. Venereol.

Sep;20(8):964-968.

Tung RC, Bergfeld WF, Vidimos AT and Remzi BK. (2000):37.

Alpha-hydroxy acid-based cosmetic procedures. Guidelines for

patient management. Am. J. Clin.Dermatol. Mar-Apr;1(2):81-88.

Windhager K and Plewig G. (1977):38. Wirkung von

Schalmitteln (Resorcin, kristalliner Schwefel, Salicylsaure) auf

Meerschweinchenepidermis. [Effects of peeling agents (resorcinol,

crystalline sulfur, salicylic acid) on the epidermis of guinea pig

(authors transl)]. Arch.Dermatol.Res. Aug 22;259(2):187-198.

Cassano N, Alessandrini G, Mastrolonardo M and Vena GA.39.(1999):Peeling agents: Toxicological and allergological aspects.

J.Eur.Acad.Dermatol.Venereol. Jul;13(1):14-23.

Bari AU, Iqbal Z and Rahman SB. (2005):40. Tolerance and

safety of superficial chemical peeling with salicylic acid in

various facial dermatoses. Indian J. Dermatol. Venereol. Leprol.

Mar-Apr;71(2):87-90.

Ahn HH and Kim IH. (2006):41. Whitening effect of salicylic

acid peels in Asian patients. Dermatol.Surg. Mar; 32(3):372-5;

discussion 375.

Pierard GE, Nikkels Tassoudji N, Arrese JE, Pierard42.

Franchimont C and Leveque JL. (1997): Dermo-

epidermal stimulation elicited by a beta-lipohydroxyacid:

A comparison with salicylic acid and all-trans-retinoic acid.

Dermatology; 194(4):398-401.


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comparative study on the effect of retinoic acid, glycolic acid and salicylic acid

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