Podophyllotoxin-induced acantholysis and cytolysis in a skin equivalent model

Skin equivalent models are used for a wide variety of pharmacotoxicological trials. The present study was performed to assess morphologically the effect of podophyllotoxin on human bioengineered skin. The untreated model exhibited many resemblances with the parent tissues, although the epidermal differentiation was slightly impaired at the ultrastructural level. The penetration of podophyllotoxin and its biological effects inside the model appeared largely increased compared to the clinical experience with the drug. Acantholysis and cytolytic changes were prominent mimicking the effect of cantharidin. The exaggerated response of many skin equivalents to various compounds shed some doubts on the validity of the model when it is used to show efficacy rather than toxicity. This might apply to claims of efficacy for cosmetic compounds. The effect of cosmetic additives cannot be validated by such approach alone.