Effects of gemfibrozil on in vitro cultured normal human skin explants

Background Several lipid-lowering agents, when given topically, show a prof ound effect on skin morphology. Because of tow bioavailability of these dru gs for keratinocytes, the incidence is extremely low clinically. The most a ppropriate way to study the effect of hypolipidemic drugs on keratinocytes is by artificial exposure of the skin to high drug concentrations. Objective To study the effects of gemfibrozil on the morphology of in vitro cultured normal human skin explants, As gemfibrozil induces barrier disrup tion by inhibiting epidermal sterologenesis, essential for a competent perm eability barrier, it is interesting to investigate the morphologic changes associated with this phenomenon. Studying the epidermal changes induced by lipid-lowering agents is important, not only because it might lead to a bet ter understanding of the effects of these drugs on keratinocytes, but as it might also unlock the door to a wider knowledge of the pathomechanism of d isorders of cornification. Methods Normal human skin from patients undergoing mastectomy was cultured in the presence of 2, 5, and 10 mM of gemfibrozil for 4 days The morphologi c changes were evaluated by three blinded observers. Their reports were mat ched and collated. Results The cultured skin in the presence of gemfibrozil showed cell crowdi ng of keratinocytes in the lower part of the epidermis, indicating epiderma l hyperplasia and increased proliferation. Intercellular edema with the for mation of small cavities in the epidermis, intracellular edema, and vacuola r alteration of keratinocytes in the upper portion of the epidermis were al so observed. The intensity of these changes tended to parallel the gemfibro zil concentration. Some dermo-epidermal detachments did not correlate with the gemfibrozil concentration, but rather with tissue characteristics pecul iar to each explant. Conclusions The morphologic changes caused by gemfibrozil to normal human s kin were not characteristic of psoriasis, and included intracellular and in tercellular edema in the upper portion of the epidermis and cell crowding, indicating epidermal hyperplasia in the lower portion of the epidermis. The present experimental study gives further supper? to the hypothesis that hy polipidemic drugs cause an initial break in the barrier function of the epi dermis, followed by a physiologic epidermal response, aimed at barrier rest oration. This rather nonspecific stimulus to epidermal proliferation may tr igger psoriasis in predisposed patients.