Interaction of UVB-absorbing Sunscreen Ingredients with Cutaneous Molecules May Alter Photoimmune Protection¶

Abstract

Studies of the photoimmunoprotective properties of sunscreens have produced disparate results. In this study in hairless mice, we compared two UVB absorbers, 2-ethylhexyl-p-methoxycinnamate (2-EHMC) and octyl-N-dimethyl-p-aminobenzoate (o-PABA), individually formulated in a common base lotion with a sunburn protection factor of 6. We measured their capacity to protect against suppression of the contact hypersensitivity (CHS) induced by three daily exposures of the dorsum to 6x the minimal erythemal/edematous dose (MED) of solar-simulated UV radiation (SSUV), in comparison with base lotion-treated mice exposed to 3 x 1 MED of SSUV. All treatments produced a similar minimal erythema. CHS was equally suppressed in mice irradiated through o-PABA and base lotion, but the suppression was significantly reduced in mice irradiated through 2-EHMC. Neither UVB absorber inhibited the epidermal photoisomerization to the immunosuppressive mediator, cis-urocanic acid. However, when mice were treated with exogenous cis-urocanic acid topically on the dorsum, but not when injected subcutaneously on the abdomen, suppression of CHS was observed in o-PABA- and base lotion-treated mice, but not in 2-EHMC-treated mice. Thus, the enhanced immunoprotection in mice irradiated through 2-EHMC apparently resulted from the direct inactivation of epidermal cis-urocanic acid by 2-EHMC. We conclude that comparative assessment of photoimmunoprotection by UV absorbers requires SSUV, erythemally matched exposures and consideration of potential interactions with cutaneous molecules.

Radiation Sources Providing Increased UVNUVB Ratios Induce Photoprotection Dependent on the UVA Dose in Hairless Mice

“…(18) found that SSUV irradiation of human subjects through a broad‐spectrum sunscreen was significantly less protective against the formation of DNA lesions (cyclobutane pyrimidine dimers and 8‐hydroxy‐2′‐deoxyguanosine) and the expression of the tumor suppressor p53 than irradiation through a UVB‐only absorbing sunscreen matched for sun protection factor. These differing findings are difficult to explain, but the nature of the UV‐absorbers, their photostability (19), their possible interaction with skin components (20), the fluence and spectral properties of the UV doses delivered through them and the indicators measured to assess immune function may be responsible.…”

Protection from Inflammation, Immunosuppression and Carcinogenesis Induced by UV Radiation in Mice by Topical Pycnogenol®¶

“…SSUV rudiurion. The SSUV (290-400 nm) source for irradiation of the mice has been described previously (22) and comprised a cellulose acetatefiltered planar bank of six fluorescent UV-A-emitting tubes (Hitachi 40W F40T lO/BL black light, Tokyo, Japan) flanking one UV-B-emitting tube (Philips TL 40W/12RS, Eindhoven, The Netherlands). Mice were irradiated unrestrained in their boxes, with the wire cage tops removed.…”

“…The base lotion used as the vehicle for PycnogenolC? or cis-UCA was a simple oil-in-water cosmetic emulsion prepared without preservatives, perfume or coloring agents and known to be innocuous on the mouse skin (22). PycnogenolB extract (Horphag Research Ltd, Geneva, Switzerland) was dissolved in dimethyl sulfoxide (DMSO) at concentrations up to 4% wt/vol and diluted with base lotion to produce lotions containing 0.02542% wt/vol of the extract and 5% vol/vol DMSO.…”

“…The vehicle control lotion ("base lotion") also contained 5% vol/vol DMSO. Trans-UCA (Sigma Aldrich Australia, Castle Hill, NSW, Australia) was photoisomerized in DMSO solution to the photostationary state, as previously described (22), and diluted with base lotion to provide a lotion of 0.2% (cis + trans)-UCA, referred to as "cis-UCA" in this study, and 5% DMSO. Control mice were treated with the base lotion containing only 5% DMSO.…”

“…lotion (or base lotion) applied also to the dorsal skin, and continuing for a further two days. On Days 8 and 9, contact hypersensitivity (CHS) was induced as previously described (22) by application of the contact sensitizer oxazolone (Sigma) to the unirradiated abdominal skin, thus assessing systemic alterations in CHS resulting from the dorsal SSUV exposure. The response wa5 elicited by challenging the ears with oxazolone on Day 15, and the peak of the ear swelling reaction was measured with the spring micrometer between 16 and 24 h. The group average ear swelling was calculated as the difference between prechallenge and challenged ear thicknesses, and the percent suppression of CHS was calculated as 100 -(average ear swelling of treated mice/average ear swelling of control mice) X 100.…”