154 The role of hyaluronan in the treatment of epidermal atrophy

Abstract

Senile skin atrophy is a common side effect of intrinsic aging and UV exposition and it affects both dermal and epidermal layers of the skin. While dermal atrophy is mostly associated with the loss of connective tissue, epidermal atrophy manifests as overall thinning of epidermis, reduction of keratinocyte size and flattening of the dermoepidermal junction. Compared to senile atrophy, steroid skin atrophy frequently arises during glucocorticoid therapy and causes serious skin damages, particularly when applied to fragile skin. The anti-atrophic potential of sodium hyaluronate (SH) has been studied previously and it was demonstrated on a group of patients affected by steroid atrophy (Kaya et al., 2006). In this study, we investigated the ability of high (1500 kDa, HMW-SH), low (320 kDa, LMW-SH) and very low (15 kDa, VLMW-SH) molecular weight SH to reverse the main signs of epidermal atrophy (viability, total protein level, MMP expression) in the model of steroid-treated HaCaT keratinocytes. We also performed two double-blind, placebo-controlled, six-week in vivo studies to evaluate the effect of VLMW-SH and LMW-SH topical application on thickness of epidermis using the method of in vivo reflectance confocal microscopy. In both studies, 28 healthy female volunteers with living epidermal thickness below 50 μm participated, applying a cream with 0,2 % VLMW-SH (1st study) or 0,2 % LMW-SH (2nd study) on the face. Our results show that VLMW-SH significantly reverses all the studied signs of steroid-induced atrophy in HaCaT keratinocytes and increases the average epidermal thickness of aged skin in vivo. HMW-SH demonstrated less pronounced effect and LMW-SH showed no significant anti-atrophic abilities neither in vitro nor in vivo. In conclusion, we confirmed the importance of SH in senile and steroid-induced skin atrophy. However, therapeutic potentials of HMW, LMW and VLMW-SH show significant differences and should be investigated in detail. These results support the beneficial effects of SH and the possibility of its application in the therapy of atrophic epidermal skin.