title: Retinoic acid synergistically enhances the melanocytotoxic and depigmenting effects of monobenzylether of hydroquinone in black guinea pig skin.
abstract: Monobenzylether of hydroquinone (MBEH) has long been utilized for the depigmentation therapy of patients with extensive vitiligo. In this approach, the normally pigmented areas surrounding vitiligo lesions are depigmented to achieve a uniform skin tone. One of the important disadvantages of MBEH therapy, however, is the resistance of a considerable number of vitiligo patients against the depigmenting effect of this agent. We have previously proposed that the glutathione-dependent cytoprotection of melanocytes can be impaired through the inhibition of the enzyme glutathione S-transferase by retinoic acid (RA). The combination of RA with melanocytotoxic agents could thus lead to increased susceptibility of melanocytes to such compounds. In this study we have shown, for the first time, that the melanocytotoxic and depigmenting effects of MBEH are synergistically enhanced when it is combined with RA. The treatment of black guinea pig skin with RA (0.025%) alone induced no significant changes in the number of epidermal melanocytes and no skin depigmentation. On the other hand, MBEH (10%) produced mild to moderate skin depigmentation and reduced the average number of melanocytes from 76 (+/-5)/field (magnification: x 40) in control sites, to 42 (+/-6)/field in the depigmented skin. The RA (0.025%)-MBEH (10%) combination, however, produced a complete degree of depigmentation in the majority of treated sites after 10 days of application and reduced the average number of melanocytes to only 6 (+/-6)/field. RA-MBEH combination serves as a very potent skin depigmenting formula and now awaits future assessments of its potential use for the treatment of extensive vitiligo.
authors.affiliation: Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. kasraeeb@sums.ac.ir
authors.forename: Behrooz
authors.initials: B
authors.lastname: Kasraee
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Fallahi
authors.forename: Gholamreza Safaee
authors.initials: GS
authors.lastname: Ardekani
authors.forename: Saeed
authors.initials: S
authors.lastname: Ebrahimi
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Doroudchi
authors.forename: Gholamhossein R
authors.initials: GR
authors.lastname: Omrani
authors.forename: Farhad
authors.initials: F
authors.lastname: Handjani
authors.forename: Mitra
authors.initials: M
authors.lastname: Amini
authors.forename: Nader
authors.initials: N
authors.lastname: Tanideh
authors.forename: Marzieh
authors.initials: M
authors.lastname: Haddadi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Nikbakhsh
authors.forename: Saeedeh
authors.initials: S
authors.lastname: Jahanbani
authors.forename: Christian
authors.initials: C
authors.lastname: Tran
authors.forename: Olivier
authors.initials: O
authors.lastname: Sorg
authors.forename: Jean-Hilaire
authors.initials: JH
authors.lastname: Saurat
mesh_terms: D000818:Animals; D003879:Dermatologic Agents / Q000494:pharmacology; D004357:Drug Synergism; D004817:Epidermis / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D006200:Hair Color / Q000187:drug effects; D006873:Hydroquinones / Q000494:pharmacology*; D008543:Melanins / Q000032:analysis; D008544:Melanocytes / Q000187:drug effects* / Q000473:pathology; D012880:Skin Pigmentation / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D003879:Dermatologic Agents; D006873:Hydroquinones; D008543:Melanins; D014212:Tretinoin; C006429:monobenzone