title: Inhibition of UVA-mediated melanogenesis by ascorbic acid through modulation of antioxidant defense and nitric oxide system.
abstract: Ascorbic acid (AA) has been well known as a skin whitening agent, although attempts have been made to evaluate its protective role against ultraviolet (UV)-induced skin hyperpigmentation or increased melanin production. While melanogenesis is a defense mechanism of the skin against UV irradiation, melanin overproduction may also contribute to melanoma initiation. UVA might play a role in melanogenesis through promoting oxidative stress, which occurs as the result of increased formation of oxidants and/or reactive nitrogen species (RNS) including nitric oxide (NO). Therefore, we investigated the antimelanogenic effect of AA (7.5-120 μM) in association with its inhibitory effect on UVA-induced oxidant formation, NO production through endothelial and inducible NO synthases (eNOS and iNOS) activation and impairment of antioxidant defense using G361 human melanoma cells. Our study demonstrated a comparable ability of AA with that of kojic acid, a well-known tyrosinase inhibitor in inhibiting mushroom tyrosinase. Melanin content was reduced by AA, but neither tyrosinase activity nor mRNA levels were reduced by AA at non-cytotoxic concentrations in UVA-irradiated G361 cells. AA was shown to inhibit UVA-mediated catalase (CAT) inactivation, glutathione (GSH) depletion, oxidant formation and NO production through suppression of eNOS and iNOS mRNA. We report herein that AA can protect against UVA-dependent melanogenesis possibly through the improvement of antioxidant defense capacity and inhibition of NO production through down-regulation of eNOS and iNOS mRNA.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. siuks@mahidol.ac.th
authors.forename: Uraiwan
authors.initials: U
authors.lastname: Panich
authors.forename: Vanida
authors.initials: V
authors.lastname: Tangsupa-a-nan
authors.forename: Tasanee
authors.initials: T
authors.lastname: Onkoksoong
authors.forename: Kamolratana
authors.initials: K
authors.lastname: Kongtaphan
authors.forename: Kanda
authors.initials: K
authors.lastname: Kasetsinsombat
authors.forename: Pravit
authors.initials: P
authors.lastname: Akarasereenont
authors.forename: Adisak
authors.initials: A
authors.lastname: Wongkajornsilp
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003879:Dermatologic Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000378:metabolism; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008545:Melanoma / Q000517:prevention & control; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D000975:Antioxidants; D003879:Dermatologic Agents; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D008543:Melanins; D012333:RNA, Messenger; D009569:Nitric Oxide; D002374:Catalase; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D014442:Monophenol Monooxygenase; D005978:Glutathione; D001205:Ascorbic Acid