EPISKIN: An in vitro model for the evaluation of phototoxicity and sunscreen photoprotective properties

Exposure to UV radiation has been shown to induce cutaneous biological changes and chemical modifications of exogenous compounds. The application of sunscreen limits UV-induced cutaneous injury. Besides damages can also be elicited by some chemicals following UV irradiation (phototoxic agents). The effects of UVA and UVB irradiation have been studied in vitro on a reconstituted epidermis (EPISKIN) for cytotoxicity (MTT conversion test) and release of a proinflammatory mediator, interleukin 1alpha. When compared with irradiated human keratinocyte monolayers, the results obtained with EPISKIN showed the protective function of the stratum corneum to UVB. Topical application of a UVB sunscreen directly on EPISKIN stratum corneum showed a concentration-dependent relationship between the active ingredients and UVB-induced damages evaluated by both parameters. When chlorpromazine was tested on EPISKIN, an increase in cytotoxicity and release of interleukin 1alpha followed UVA irradiation. A non-cytotoxic dose of 10 J/cm2 of UVA induced a 20-fold decrease in the chlorpromazine IC50. The chlorpromazine-induced inflammatory reaction was also reflected by a more intense release of interleukin 1alpha in the underlying media of EPISKIN. Thus this proinflammatory mediator seems to be relevant as a phototoxic marker. The EPISKIN model may be a useful tool in the study of UV-induced cutaneous damage. The design of this study represents an advance in non-animal test development and could be of great interest in the determination of phototoxic or photoprotective effects of compounds in vitro.