PODOPHYLLOTOXIN-INDUCED ACANTHOLYSIS AND CYTOLYSIS IN A SKIN EQUIVALENT MODEL

Skin equivalent models are used for a wide variety of pharmacotoxicolo gical trials. The present study was performed to assess morphologicall y the effect of podophyllotoxin on human bioengineered skin. The untre ated model exhibited many resemblances with the parent tissues, althou gh the epidermal differentiation was slightly impaired at the ultrastr uctural level. The penetration of podophyllotoxin and its biological e ffects inside the model appeared largely increased compared to the cli nical experience with the drug. Acantholysis and cytolytic changes wer e prominent mimicking the effect of cantharidin. The exagerated respon se of many skin equivalents to various compounds shed some doubts on t he validity of the model when it is used to show efficacy rather than toxicity. This might apply to claims of efficacy for cosmetic compound s. The effect of cosmetic actives cannot be validated by such approach alone.