Podophyllotoxin-Induced Acantholysis and Cytolysis in a Skin Equivalent Model

Abstract

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.

Recent Progress on C‐4‐Modified Podophyllotoxin Analogs as Potent Antitumor Agents

“…Studies on penetration of PPT into human bioengineered skin have demonstrated that PPT analogs induce acantholysis and cytolysis in this skin‐equivalent model . We reported that PPT derivatives exhibit insecticidal activity against some economically important insects, more promising and pronounced activity as compared with PPT .…”

Comparative Surfactant Reactivity of Canine and Human Stratum Corneum: A Plea for the Use of the Corneosurfametry Bioassay

“…The other relies on in vitro models with excised human skin or its alternatives, such as cell cultures, refined bioengineered skin, and epidermal or dermo-epidermal equivalents (6,7). A series of these procedures appears to predict the in vivo outcome, although they react strongly, and probably excessively, in comparison to the in vivo situation (8). As the process of irritation is complex, no single parameter or study endpoint has yet emerged as the ideal predictor of skin irritation.…”