Volume 62, Issue 3 , Pages 511-513, March 2010
Decrease of ultraviolet A light–induced “common deletion” in healthy volunteers after oral Polypodium leucotomos extract supplement in a randomized clinical trial
Article Outline
To the Editor: Ultraviolet (UV) radiation causes sunburn, immunosuppression, pigmentary changes, photoaging, and skin cancer in a wavelength-dependent fashion. More than 95% of the incident UV radiation is ultraviolet A (UVA; 320-400 nm), which penetrates into the dermis. It induces DNA damage through the formation of reactive oxygen species (ROS), which are involved in oxidative base damage. ROS also induce matrix metalloproteinase (MMP) upregulation, which is partially responsible for skin photoaging.1
The common deletion (CD) is a 4977 base pair–long mitochondrial DNA whose deletion is induced by, and is a marker of, chronic UVA radiation in fibroblasts and keratinocytes.2, 3 Polypodium leucotomos is an extract of a fern species marketed for the management of psoriasis, vitiligo, autoimmune diseases, and the prevention of photodamage/aging. P leucotomos contains polyphenols, which are potent ROS inhibitors with antiinflammatory, antioxidant, and photoprotective properties both in vitro and in vivo.4 At low concentrations, P leucotomos inhibits MMP-1 photoinduced membrane damage and reduces psoralen/UVA-induced phototoxicity.1, 5
This randomized, investigator-blinded, controlled, institutional review board–approved study was designed to detect and quantify P leucotomos' UVA-induced photoaging marker, the CD, in P leucotomos–treated and nontreated subjects after UVA irradiation.
Ten healthy volunteers between 29 and 54 years of age with Fitzpatrick skin types II and III were enrolled in a study (Fig 1). Exclusion criteria included subjects with a history of current or planned pregnancy, skin cancer, photosensitivity, radiation (other than sunlight) or asbestos exposure, smoking during the previous 6 months, subjects taking any drug that might alter skin responses to UV radiation, and subjects who were unable to undergo skin biopsies. Subjects were instructed not to change their normal photoprotection practices during the study.
Fig 1.
Flow diagram summarizing participant flow, numbers and timing of randomization assignment, interventions, and measurements for each randomized group.
Each subject underwent a pretreatment 3-mm punch biopsy from the proximal right volar forearm skin that was bisected for CD determination by semiquantitative real-time polymerase chain reaction and stained with hematoxylin–eosin to obtain a baseline histology. Each subject's left volar forearm was covered with a UVA opaque fenestrated adhesive patch (DV Die Cutting Inc, Danvers, MA). UVA was then administered to the left volar forearm for UVA minimal erythema dose (MED-A) determination using an Ultralite Hand/Foot Unit (Model HA 1200 12 UVA, FA 1200, AC voltage 115, amp 12, frg 50/60 Hz, with light bulbs model: F36T12-BL emitting wavelengths of 320-400 nm with a peak in 350 nm as a light source [Ultralite Enterprises Inc, Lawrenceville, GA]). The windows were exposed to 10, 15, 20, 25, 30, or 35 J/cm2 doses of UVA light. One week later, those subjects randomized not to receive any oral treatment were exposed to 2 and 3 times their MED-A to their right volar forearm, through a UVA opaque fenestrated adhesive patch, while those subjects randomized to receive oral P leucotomos were administered PL 240 mg 8 and 2 hours before exposure to two to three times their MED-A in the same areas. Each subject had a second and a third 3-mm punch biopsy specimen taken 24 hours later from the two irradiated areas and a fourth biopsy specimen taken from an adjacent nonirradiated (ie, shielded) site. These specimens were bisected for CD determination and hematoxylin-eosin staining. A histologic examination showed mild superficial perivascular inflammatory lymphocytic infiltrates in the majority of the control group's irradiated sites. Baseline CD could not be quantified in two subjects in the non-P leucotomos–treated group; they were excluded from the subsequent analysis.
At two times the MED, average CD values in the non-P leucotomos–treated group increased by 217% over baseline, while values in the P leucotomos–treated decreased by 84% (P = .06). At three times the MED, those values increased 760% and 61%, respectively (P = .07). No interaction significance was found (P = .08).
Pretreatment with P leucotomos showed a strong trend but failed to achieve statistical significance in preventing the increase of CD levels 24 hours after UVA irradiation. Although chronic UVA exposure has been associated with CD elevation,2, 3 our findings showed increments in CD expression after acute UVA exposure. According to our interaction analysis, P leucotomos' effect exhibited a trend towards preventing the increase of CD levels as the UVA dose increased. Except for the expected erythema after UVA irradiation, no treatment-related adverse events were recorded in any of the subjects.
Although pretreatment with P leucotomos did not prevent the development of mild superficial perivascular inflammatory lymphocytic infiltrate in subjects irradiated with UVA, more biopsies in the control group (those not receiving P leucotomos; n = 6) reported the development of the infiltrate after UVA irradiation compared with biopsy reports in the PL group (n = 5) after irradiation with UVA. In addition, all biopsies from adjacent nonirradiated (ie, shielded) sites reported normal skin (ie, no infiltrates).
Although larger studies are needed to characterize P leucotomos' role in photoaging, this pilot study's findings suggest that P leucotomos may prevent UVA-induced skin photodamage possibly by preventing UVA-dependent mitochondrial DNA damage.
References
- . Predominant effects of Polypodium leucotomos on membrane integrity, lipid peroxidation, and expression of elastin and matrixmetalloproteinase-1 in ultraviolet radiation exposed fibroblasts, and keratinocytes. J Dermatol Sci. 2003;32:1–9
- Singlet oxygen mediates the UVA-induced generation of the photoaging-associated mitochondrial common deletion. J Biol Chem. 1999;274:15345–15349
- Induction of the photoaging-associated mitochondrial common deletion in vivo in normal human skin. J Invest Dermatol. 2004;122:1277–1283
- Polypodium leucotomos extract: antioxidant activity and disposition. Toxicol In Vitro. 2006;20:464–471
- . Polypodium leucotomos extract inhibits transurocanic acid photoisomerization and photodecomposition. J Photochem Photobiol B. 2006;82:173–179
Supported by a 2008 Women's Dermatologic Society Academic Research Grant awarded to Adriana Villa, MD.
Conflicts of interest: None declared.
PII: S0190-9622(09)00693-8
doi:10.1016/j.jaad.2009.05.045
© 2009 American Academy of Dermatology, Inc. Published by Elsevier Inc All rights reserved.
Volume 62, Issue 3 , Pages 511-513, March 2010
