EFFECT OF RETINYL PALMITATE ON SKIN 239 tissue, note that changes in skin composition and the epidermal proliferative changes are also apparent. DISCUSSION Cosmetic materials are generally accepted to have a minimal effect on skin biology. The proven benefits of the application of cosmetic skin treatment products have usually been attributed to a moisturization effect. One particular material used in cosmetic formula- tions, vitamin A, is known to have systemic physiological and biochemical effects (7,13). All of the physiological functions of retinoids (such as the requirement for normal vision and reproduction) cannot be satisfied by retinoic acid (7). Indeed, these functions seem to be adequately satisfied by retinol. However, the role of retinoids in the regulation of skin development seems to be best satisfied by retinoic acid. Thus, part of the actions of retinyl palmitate in skin may depend on its conversion to retinoic acid (13). This conversion depends on the enzymatic cleavage of the ester bond in the retinyl palmitate. Nonspecific esterase enzyme activity exists within skin (14). In addi- tion, the skin must be able to oxidize the retinol to retinoic acid. It has been demon- strated that skin preparations can indeed convert retinyl to retinoic acid (15). Although it has been known that retinyl palmitate has the potential to effect a change of skin composition and physiology, this potential has never been examined. Retinoids, in general, prevent connective tissue atrophy. This prevention of atrophy is probably mediated by an inhibition of collagenolytic activity (16). In addition, dermal repair in response to UV damage, which is accelerated by retinoic acid administration, appears to involve a zone of regenerating connective tissue (17). Although retinoids inhibit collagen synthesis (3,5,18), they do promote glycosaminoglycan synthesis (5,19,20). Therefore, some of the effects of retinoids in terms of altering dermal com- position can be thought of as due to an inhibition of connective tissue breakdown and a promotion of the synthesis of glycosaminoglycans. This hypothesis is .supported by the observed changes in skin composition following treatment with retinyl palmitate. The increase of DNA content within the skin can be partially explained by the influx of inflammatory cells into the skin. Although there was an increase of skin DNA content following treatment with 0.1% retinyl palmitate, this was the maximal response. There is then a decrease of DNA content with increasing concentrations of retinyl palmitate. This may be due to the inhibitory effect of high concentrations of retinoids on both cell mobility and cellular proliferative capacity (18,21). However, at the highest dose ad- ministered (5 %), there was a tremendous increase in DNA content. This may be due to an irritant/inflammatory response to the application of the retinoid. Of interest in this study is that even with irritation present, there was little or no change in the punch biopsy weight. This suggests that the response is not significantly mediated by an edematous response. Finally, retinyl palmitate administration causes an accumulation of collagen within the dermis. These changes indicate that although there is an irritation response in the skin treated with RP, there is also a significant effect on the collagen content within the dermis. This alteration of the collagen content is unlikely to be due to an irritation response.

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