Chemical and instrumental approaches to treat hyperpigmentation.

Many modalities of treatment for acquired skin hyperpigmentation are available including chemical agents or physical therapies, but none are completely satisfactory. Depigmenting compounds should act selectively on hyperactivated melanocytes, without short- or long-term side-effects, and induce a permanent removal of undesired pigment. Since 1961 hydroquinone, a tyrosinase inhibitor, has been introduced and its therapeutic efficacy demonstrated, and other whitening agents specifically acting on tyrosinase by different mechanisms have been proposed. Compounds with depigmenting activity are now numerous and the classification of molecules, based on their mechanism of action, has become difficult. Systematic studies to assess both the efficacy and the safety of such molecules are necessary. Moreover, the evidence that bleaching compounds are fairly ineffective on dermal accumulation of melanin has prompted investigations on the effectiveness of physical therapies, such as lasers. This review which describes the different approaches to obtain depigmentation, suggests a classification of whitening molecules on the basis of the mechanism by which they interfere with melanogenesis, and confirms the necessity to apply standardized protocols to evaluate depigmenting treatments.

[1]  L. Packer,et al.  Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line. , 1999, Free radical biology & medicine.

[2]  W. Smith The Effects of Topical L(+) Lactic Acid and Ascorbic Acid on Skin Whitening , 1999, International journal of cosmetic science.

[3]  M. d’Ischia,et al.  Mechanism of inhibition of melanogenesis by hydroquinone. , 1991, Biochimica et biophysica acta.

[4]  P. Bossuyt,et al.  The development of guidelines for the treatment of vitiligo. Clinical Epidemiology Unit of the Istituto Dermopatico dell'Immacolata-Istituto di Recovero e Cura a Carattere Scientifico (IDI-IRCCS) and the Archives of Dermatology. , 1999, Archives of dermatology.

[5]  A. Fleischer,et al.  The combination of 2% 4-hydroxyanisole (Mequinol) and 0.01% tretinoin is effective in improving the appearance of solar lentigines and related hyperpigmented lesions in two double-blind multicenter clinical studies. , 2000, Journal of the American Academy of Dermatology.

[6]  P. Riley,et al.  Tyrosinase kinetics: failure of acceleration in oxidation of ring-blocked monohydric phenol substrate. , 1998, Pigment cell research.

[7]  M. Tachibana,et al.  MITF: a stream flowing for pigment cells. , 2000, Pigment cell research.

[8]  Youngsoo Kim,et al.  Oxyresveratrol and Hydroxystilbene Compounds , 2002, The Journal of Biological Chemistry.

[9]  A. Chakraborty,et al.  Effect of arbutin on melanogenic proteins in human melanocytes. , 1998, Pigment cell research.

[10]  E. Sharlow,et al.  An alternative approach to depigmentation by soybean extracts via inhibition of the PAR-2 pathway. , 2001, The Journal of investigative dermatology.

[11]  L. Packer,et al.  alpha-Lipoic acid as a biological antioxidant. , 1995, Free radical biology & medicine.

[12]  Sungnack Lee,et al.  Intermittent Therapy for Melasma in Asian Patients with Combined Topical Agents (Retinoic Acid, Hydroquinone and Hydrocortisone): Clinical and Histological Studies , 1998, The Journal of dermatology.

[13]  V. Virador,et al.  Effects of all-trans retinoic acid on melanogenesis in pigmented skin equivalents and monolayer culture of melanocytes. , 2001, Journal of dermatological science.

[14]  F. Solano,et al.  Inhibition of melanogenesis in response to oxidative stress: transient downregulation of melanocyte differentiation markers and possible involvement of microphthalmia transcription factor. , 2001, Journal of cell science.

[15]  C. Smith,et al.  Selective cytotoxicity of hydroquinone for melanocyte-derived cells is mediated by tyrosinase activity but independent of melanin content. , 1988, Pigment cell research.

[16]  J. Voorhees,et al.  Differential regulation of tyrosinase activity in skin of white and black individuals in vivo by topical retinoic acid. , 1993, The Journal of investigative dermatology.

[17]  T. Hamilton,et al.  Topical tretinoin (retinoic acid) treatment for liver spots associated with photodamage. , 1992, The New England journal of medicine.

[18]  A. Napolitano,et al.  Peroxidase as an alternative to tyrosinase in the oxidative polymerization of 5,6-dihydroxyindoles to melanin(s). , 1991, Biochimica et biophysica acta.

[19]  R. Anderson,et al.  Ineffective treatment of refractory melasma and postinflammatory hyperpigmentation by Q-switched ruby laser. , 1994, The Journal of dermatologic surgery and oncology.

[20]  B. Kasraee Peroxidase-Mediated Mechanisms Are Involved in the Melanocytotoxic and Melanogenesis-Inhibiting Effects of Chemical Agents , 2002, Dermatology.

[21]  V. Kahn Effect of kojic acid on the oxidation of DL-DOPA, norepinephrine, and dopamine by mushroom tyrosinase. , 1995, Pigment cell research.

[22]  G. Ghanem,et al.  Glutathione depletion increases tyrosinase activity in human melanoma cells. , 1993, The Journal of investigative dermatology.

[23]  F. Camacho,et al.  Management of Facial Hyperpigmentation , 2000, American journal of clinical dermatology.

[24]  S. Passi,et al.  Molecular basis of substrate and inhibitory specificity of tyrosinase: phenolic compounds , 1981, The British journal of dermatology.

[25]  T. Cruz,et al.  Reactive Oxygen Species Mediate Cytokine Activation of c-Jun NH2-terminal Kinases* , 1996, The Journal of Biological Chemistry.

[26]  C. Antoniou,et al.  Melasma. Classification and treatment , 1995 .

[27]  J. Lim,et al.  Treatment of melasma using kojic acid in a gel containing hydroquinone and glycolic acid. , 1999, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[28]  E. Monzani,et al.  Inhibition of the catecholase activity of biomimetic dinuclear copper complexes by kojic acid , 2000, JBIC Journal of Biological Inorganic Chemistry.

[29]  M. Ichihashi,et al.  Linoleic acid and α-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin , 1998, Archives of Dermatological Research.

[30]  L. Bowes,et al.  Combination treatment of melasma with pulsed CO2 laser followed by Q-switched alexandrite laser: a pilot study. , 1999, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[31]  R. R. Anderson Lasers in Dermatology—A Critical Update , 2000, The Journal of dermatology.

[32]  D. Bandyopadhyay,et al.  Dexamethasone makes the gastric mucosa susceptible to ulceration by inhibiting prostaglandin synthetase and peroxidase - two important gastroprotective enzymes , 1999, Molecular and Cellular Biochemistry.

[33]  B. Fanburg,et al.  Activation of an H2O2-generating NADH Oxidase in Human Lung Fibroblasts by Transforming Growth Factor β1 (*) , 1995, The Journal of Biological Chemistry.

[34]  Masuda,et al.  In vitro and in vivo evaluation of ellagic acid on melanogenesis inhibition , 2000, International journal of cosmetic science.

[35]  S. Kunachak,et al.  Dermabrasion: A Curative Treatment for Melasma , 2001, Aesthetic Plastic Surgery.

[36]  E. Aberdam,et al.  Retinoic acid as modulator of UVB-induced melanocyte differentiation. Involvement of the melanogenic enzymes expression. , 1994, Journal of cell science.

[37]  T. Yamamura,et al.  Antimelanogenic activity of hydrocoumarins in cultured normal human melanocytes by stimulating intracellular glutathione synthesis , 2002, Archives of Dermatological Research.

[38]  G. Habermehl,et al.  Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha. , 1989, The Biochemical journal.

[39]  E. L. Isaacson,et al.  Inhibition of UVR-induced tanning and immunosuppression by topical applications of vitamins C and E to the skin of hairless (hr/hr) mice. , 2000, Pigment cell research.

[40]  G. Imokawa,et al.  The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms of mitogenesis and melanogenesis. , 1997, Pigment cell research.

[41]  G. Imokawa,et al.  Selective aberration and pigment loss in melanosomes of malignant melanoma cells in vitro by glycosylation inhibitors: premelanosomes as glycoprotein. , 1983, The Journal of investigative dermatology.

[42]  L. Goldman,et al.  Laser Treatment of Tattoos: A Preliminary Survey of Three Year's Clinical Experience , 1967 .

[43]  Bhushan Kumar,et al.  Safety and efficacy of glycolic acid facial peel in Indian women with melasma , 2001, International journal of dermatology.

[44]  R. Dwek,et al.  Protein specific N-glycosylation of tyrosinase and tyrosinase-related protein-1 in B16 mouse melanoma cells. , 1999, The Biochemical journal.

[45]  T. Sugai Clinical Effects of Arbutin in Patients with Chloasma , 1992 .

[46]  Sun-Lim Choi,et al.  Aloesin inhibits hyperpigmentation induced by UV radiation , 2002, Clinical and experimental dermatology.

[47]  K. Arndt,et al.  Laser treatment of pigmented lesions--2000: how far have we gone? , 2000, Archives of dermatology.

[48]  B. Kasraee Depigmentation of brown Guinea pig skin by topical application of methimazole. , 2002, The Journal of investigative dermatology.

[49]  K. Wittern,et al.  The inhibitory effect of DL-alpha-tocopheryl ferulate in lecithin on melanogenesis. , 1997, Anticancer research.

[50]  V. Hearing,et al.  A standardized protocol for assessing regulators of pigmentation. , 1999, Analytical biochemistry.

[51]  E. Sharlow,et al.  The protease-activated receptor-2 upregulates keratinocyte phagocytosis. , 2000, Journal of cell science.

[52]  J. H. Chung,et al.  Ceramide inhibits cell proliferation through Akt/PKB inactivation and decreases melanin synthesis in Mel-Ab cells. , 2001, Pigment cell research.

[53]  T. Hamilton,et al.  Topical tretinoin (retinoic acid) therapy for hyperpigmented lesions caused by inflammation of the skin in black patients. , 1993, The New England journal of medicine.

[54]  S. Sohn,et al.  Melasma: histopathological characteristics in 56 Korean patients , 2002, The British journal of dermatology.

[55]  J. Pezzuto,et al.  Resveratrol Inhibits Cyclooxygenase-2 Transcription and Activity in Phorbol Ester-treated Human Mammary Epithelial Cells* , 1998, The Journal of Biological Chemistry.

[56]  R. Varón,et al.  Action Mechanism of Tyrosinase on meta- and para-Hydroxylated Monophenols , 2000, Biological chemistry.

[57]  T. Nishiyama,et al.  Fused Heterocyclic Antioxidants: Antioxidative Activities of Hydrocoumarins in a Homogeneous Solution , 2001, Bioscience, biotechnology, and biochemistry.

[58]  G. Babcock,et al.  Inhibition of melanosome transfer from melanocytes to keratinocytes by lectins and neoglycoproteins in an in vitro model system. , 2001, Pigment cell research.

[59]  Abraham G. Novick,et al.  Classification and Treatment , 1958 .

[60]  K. Kilgore,et al.  Development of an in vitro primary screen for skin depigmentation and antimelanoma agents. , 1994, Skin pharmacology : the official journal of the Skin Pharmacology Society.

[61]  S. J. Lee,et al.  Aloesin and arbutin inhibit tyrosinase activity in a synergistic manner via a different action mechanism , 1999, Archives of pharmacal research.

[62]  C. A. Ramsden,et al.  Melanogenesis-targeted anti-melanoma pro-drug development: effect of side-chain variations on the cytotoxicity of tyrosinase-generated ortho-quinones in a model screening system. , 1997, European journal of cancer.

[63]  V. Hearing,et al.  A melanocyte-keratinocyte coculture model to assess regulators of pigmentation in vitro. , 2002, Analytical biochemistry.

[64]  A. Kligman,et al.  A new formula for depigmenting human skin. , 1975, Archives of dermatology.

[65]  R. Halaban,et al.  Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[66]  D. Bucks,et al.  Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo. , 1996, Journal of the American Academy of Dermatology.

[67]  G. Prota CHAPTER 1 – AN INTRODUCTION TO MELANIN RESEARCH , 1992 .

[68]  H. Watabe,et al.  All-trans retinoic acid induces differentiation and apoptosis of murine melanocyte precursors with induction of the microphthalmia-associated transcription factor. , 2002, The Journal of investigative dermatology.

[69]  C. Hansson,et al.  Tyrosinase-mediated formation of a reactive quinone from the depigmenting agents, 4-tert-butylphenol and 4-tert-butylcatechol. , 2000, Pigment cell research.

[70]  E. Sharlow,et al.  Inhibition of melanosome transfer results in skin lightening. , 2000, The Journal of investigative dermatology.

[71]  Bernard,et al.  Resveratrol: an original mechanism on tyrosinase inhibition , 2000, International journal of cosmetic science.

[72]  M. Ichihashi,et al.  Possible involvement of proteolytic degradation of tyrosinase in the regulatory effect of fatty acids on melanogenesis. , 1999, Journal of lipid research.

[73]  Y. Kubota,et al.  The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. , 1998, Pigment cell research.

[74]  J. Pawelek,et al.  Enhancement of the depigmenting effect of hydroquinone by cystamine and buthionine sulfoximine , 1995, The British journal of dermatology.

[75]  M. Mersel,et al.  Depigmenting effects of calcium D-pantetheine-S-sulfonate on human melanocytes. , 2000, Pigment Cell Research.

[76]  K. Jimbow,et al.  The in vivo melanocytotoxicity and depigmenting potency of N‐2,4‐acetoxyphenyl thioethyl acetamide in the skin and hair , 1995, The British journal of dermatology.

[77]  E. Rosengren,et al.  Hydrogen peroxide as an inducer of elevated tyrosinase level in melanoma cells. , 1993, The Journal of investigative dermatology.

[78]  Y. Tsuji,et al.  Selective down-regulation of tyrosinase family gene TYRP1 by inhibition of the activity of melanocyte transcription factor, MITF. , 2002, Nucleic acids research.

[79]  L. Smith,et al.  Structure-Function Relationship of Lipoprotein Lipase-mediated Enhancement of Very Low Density Lipoprotein Binding and Catabolism by the Low Density Lipoprotein Receptor , 1996, The Journal of Biological Chemistry.

[80]  R.R. Anderson,et al.  Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. , 1983, Science.

[81]  S. Im,et al.  Increased expression of α‐melanocyte‐stimulating hormone in the lesional skin of melasma , 2002, The British journal of dermatology.

[82]  K Takahashi,et al.  Functional Analysis of Microphthalmia-associated Transcription Factor in Pigment Cell-specific Transcription of the Human Tyrosinase Family Genes* , 1997, The Journal of Biological Chemistry.

[83]  Norman R. Farnsworth,et al.  Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes , 1997, Science.

[84]  K. Ahn,et al.  Kojic acid, a potential inhibitor of NF-κB activation in transfectant human HaCaT and SCC-13 cells , 2001, Archives of pharmacal research.

[85]  E. Sharlow,et al.  The protease-activated receptor 2 regulates pigmentation via keratinocyte-melanocyte interactions. , 2000, Experimental cell research.

[86]  M. Metwalli,et al.  Topical liquiritin improves melasma , 2000, International journal of dermatology.

[87]  G. Piérard,et al.  Assessment of Topical Hypopigmenting Agents on Solar Lentigines of Asian Women , 2002, Dermatology.

[88]  M. Fukuda,et al.  Arbutin: mechanism of its depigmenting action in human melanocyte culture. , 1996, The Journal of pharmacology and experimental therapeutics.

[89]  F. García-Cánovas,et al.  Effect of L-ascorbic acid on the monophenolase activity of tyrosinase. , 1993, The Biochemical journal.

[90]  G. Hautmann,et al.  Laser tissue interaction in epidermal pigmented lesions , 2001, Journal of the European Academy of Dermatology and Venereology : JEADV.

[91]  Mei Hong,et al.  Modulation of melanogenesis by aloesin: a competitive inhibitor of tyrosinase. , 2002, Pigment cell research.

[92]  A. Kanwar,et al.  A Comparative Study of 20% Azelaic Acid Cream Monotherapy versus a Sequential Therapy in the Treatment of Melasma in Dark-Skinned Patients , 2002, Dermatology.

[93]  R. Kondo,et al.  Novel vitamin E derivative with 4-substituted resorcinol moiety has both antioxidant and tyrosinase inhibitory properties , 2001, Lipids.

[94]  Jeong-Hill Park,et al.  Mushroom tyrosinase inhibition activity of some chromones. , 2002, Chemical & pharmaceutical bulletin.

[95]  E. Vass,et al.  Hydrogen peroxide generation associated with the oxidations of the eumelanin precursors 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid , 1996, Melanoma research.

[96]  C. Smith,et al.  Depigmenting action of hydroquinone depends on disruption of fundamental cell processes. , 1984, The Journal of investigative dermatology.

[97]  G. Hillebrand,et al.  The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer , 2002, The British journal of dermatology.

[98]  A. Hachiya,et al.  Biochemical Characterization of Endothelin-converting Enzyme-1α in Cultured Skin-derived Cells and Its Postulated Role in the Stimulation of Melanogenesis in Human Epidermis* , 2002, The Journal of Biological Chemistry.

[99]  Y. T. Li,et al.  Comparison of the frequency-doubled Q-switched Nd:YAG laser and 35% trichloroacetic acid for the treatment of face lentigines. , 1999, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[100]  G. S. Gukasyan Study of the Kinetics of Oxidation of Monophenols by Tyrosinase. The Effect of Reducers , 2002, Biochemistry (Moscow).

[101]  J. Sánchez,et al.  A Hydroquinone Solution in the Treatment of Melasma , 1982, International Journal of Dermatology.

[102]  H. Glatt,et al.  Inhibitors of mammalian melanocyte tyrosinase: in vitro comparisons of alkyl esters of gentisic acid with other putative inhibitors. , 1999, Biochemical pharmacology.

[103]  G. Prota,et al.  Melanins and melanogenesis , 1992 .

[104]  A. Pandya,et al.  Melasma treated with hydroquinone, tretinoin, and a fluorinated steroid , 2001, International journal of dermatology.

[105]  M. Seiberg Keratinocyte-melanocyte interactions during melanosome transfer. , 2001, Pigment cell research.

[106]  G. Imokawa,et al.  Functional analysis of tyrosinase isozymes of cultured malignant melanoma cells during the recovery period following interrupted melanogenesis induced by glycosylation inhibitors. , 1984, The Journal of investigative dermatology.

[107]  K. Jimbow,et al.  Comparison of in vitro cytotoxicity of N‐acetyl and N‐propionyl derivatives of phenolic thioether amines in melanoma and neuroblastoma cells and the relationship to tyrosinase and tyrosine hydroxylase enzyme activity , 2000, Melanoma research.

[108]  Torello Lotti,et al.  European Handbook of Dermatological Treatments , 2000, Springer Berlin Heidelberg.

[109]  T. Yamashita,et al.  Selective incorporation and specific cytocidal effect as the cellular basis for the antimelanoma action of sulphur containing tyrosine analogs. , 1999, The Journal of investigative dermatology.

[110]  F. Yang,et al.  Effects of 4-tertiary butylphenol on the tyrosinase activity in human melanocytes. , 1999, Pigment cell research.

[111]  J. Chung,et al.  Delayed ERK activation by ceramide reduces melanin synthesis in human melanocytes. , 2002, Cellular signalling.

[112]  A. Nias,et al.  Effect of azelaic acid on melanoma cells in culture , 1995, Experimental dermatology.

[113]  A. DeCaprio The toxicology of hydroquinone--relevance to occupational and environmental exposure. , 1999, Critical reviews in toxicology.