Summary
Amiprilose hydrochloride has been shown to inhibit the proliferation of a number of hyperproliferative cell types including psoriatic skin cells. In the present study, the effects of amiprilose hydrochloride on human tissue equivalents were examined by incubating a) dermal equivalents, b) skin equivalents in the process of epidermalization, and c) mature skin equivalents, with varying concentrations of the drug. In all three models amiprilose hydrochloride concentrations of 0.1% (wt/vol) and lower were not toxic to fibroblasts and keratinocytes and did not interfere with the differentiation of the skin equivalent and the developing skin equivalent. When tested in dermal equivalents, concentrations of amiprilose hydrochloride between 0.1 and 0.5% resulted in changes in fibroblast morphology with development of large intracellular vacuoles, and concentrations greater than 5% were toxic. In mature skin equivalents, in addition to changes in fibroblast morphology, amiprilose hydrochloride in concentrations of 1 to 10% affected the epidermis. When 0.5% amiprilose hydrochloride was present in the developing skin equivalent during differentiation, the epidermal keratinocytes were also affected. Thus the morphology of basal keratinocytes was modified, the differentiation was incomplete, and the dermalepidermal attachment was compromised. These studies suggest the possibility of an extracellular mechanism of action of amiprilose hydrochloride and delineate acceptable dosage ranges for the potential drug.
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Supported in part by research grant AG01274 from the National Institutes of Health, Bethesda, MD, The R. A. Welch Foundation (B0502), The Texas Advanced Technology and Research Program (Wound Healing and Aging no. 2147), and Greenwich Pharmaceuticals, Inc. R. W. G. is the recipient of a MERIT award from the National Institute on Aging, Bethesda, MD.
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Hevelone, J.C., Dimitrijevich, S.D. & Gracy, R.W. Effects of amiprilose hydrochloride on the components of human skin equivalents. In Vitro Cell Dev Biol - Animal 27, 387–396 (1991). https://doi.org/10.1007/BF02630958
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DOI: https://doi.org/10.1007/BF02630958