| Abstrakt: |
Phototoxicity inducing in vivophotoirritation, a reversible inflammatory reaction of the skin after chemical contact and UVA radiation exposure, is increasingly observed as a side effect associated with the use of both cosmetics and systemic drugs. In order to systematically screen for the phototoxic potential of new compounds, we propose two three‐dimensional models suitable for in vitrotesting: a dermal equivalent (DE) and a skin equivalent (SE) model. The DE model includes a collagen‐glycosaminoglycans‐chitosan porous matrix populated by normal human fibroblasts. The SE model is made by seeding normal human keratinocytes onto the DE, leading to a fully differentiated epidermis. The objectives of this pilot study are: 1) to compare the deleterious effects of UVA radiation on the two models and 2) to evaluate to what extent the in vitroresults can predict the in vivophototoxicity caused by well‐known photoirritant compounds, included in the COLIPA validation phototoxicity reference chemical list. Dilutions of thiourea, sulisobenzone, promethazine, chlorpromazine and tetracycline were applied (20 μl) onto DEs and SEs (n= 6) and incubated for 1 h (or 15 h) at 37°C. Irradiated samples received 3 J/cm2UVA. The 24 h post‐irradiation residual cellular viability was measured using the MTT test on treated and untreated tissues and IL‐1α release measurement in collected SE culture media. A concordance in terms of photoirritant/non‐photoirritant was obtained between the in vivodata and the in vitroresults, suggesting that the DE and the SE models could be integrated, after a complete validation study, into a protocol for in vitrotesting of the photoirritant potential of new molecules. |
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