RESUMEN
Vitamin A is important for epithelial cell proliferation and differentiation. Synthetic vitamin A derivatives, known as retinoids, have been extensively used in the last few years to treat a variety of clinical skin conditions. The aim of this study was to evaluate the histological changes in rat thin skin that might result from long term exposure to a retinoid derivative [tretinoin] and the possibility of recovery after its withdrawal. Thirty adult male albino rats were divided into three equal groups; control group, tretinointreated group, and the third group was topically treated with tretinoin cream for four weeks, then the animals were left without treatment for another four weeks. Skin specimens were processed and stained with haematoxylin and eosin and with Mallory's trichrome stain while ultrathin sections were contrasted with uranyl acetate and lead citrate. The epidermal thickness was measured and the results were statistically analysed. The effect of tretinoin on cell proliferation was further evaluated immunohistochemically using the proliferating cell nuclear antigen [PCNA]. Specimens from tretinoin-treated animals showed focal vacuolation of the keratinocytes with widening of intercellular spaces, an increase in keratohyalin granules of stratum granulosum and disorganized cells of stratum corneum. There was also a statistically highly significant increase in the epidermal thickness. The dermis showed increased collagen content and cellular infiltration mainly formed of fibroblasts. Immunohistochemical study revealed a highly significant increase in PCNA-positive nuclei in the epidermal cells. The recovery group showed mild affection of skin structure. Long-term exposure to tretinoin may induce structural changes in rat skin, being partially reversible after withdrawal of the drug. Therefore, the use of tretinoin should be restricted to the advice of dermatologists