1310 Anti-aging effects of retinoid hydroxypinacolone retinoate on skin models

Tretinoin, also known as all-trans retinoic acid (ATRA), is well-known for its anti-aging effects on skin. However, skin irritation, photochemical instability, and concerns about toxicity have hindered the use of ATRA in cosmetic products. Therefore, it is desirable to find new molecules that have increased retinoic acidlike activity without the negative side effects. Hydroxypinacolone retinoate (HPR) is a cosmetic grade ester of ATRA that has been shown to have innate retinoic acid activity without causing skin irritation. Here, we compared levels of gene transcription by HPR, ATRA, retinol (ROL), retinaldehyde (RAL), and retinyl palmitate (RP) in DNA using a retinoic acid response element (RARE) reporter assay. In addition, we compared the anti-aging properties of HPR to ATRA by testing the effects on collagen levels and skin irritation in organotypic skin models. Skin models were treated for 5 days with HPR and ATRA, basal media was collected for ELISA analysis, and skins were stained with Massons trichrome (for collagen). RARE assay results showed that HPR had greater levels of gene transcription than ROL, RAL, and RP at the same concentrations, and was less cytotoxic to cells at a 10 times higher concentration; however, HPR did not achieve gene transcription levels of ATRA. Skins treated with HPR significantly increased pro-collagen production as compared with untreated control skins, and was comparable to ATRA. Histological staining of skins for collagen corroborated these results, with the highest dose of HPR out-performing ATRA. IL-1α ELISA analysis showed that HPR did not induce more (or less) inflammatory response than either ATRA or the vehicle control. Together these data suggest that HPR is an effective alternative to ATRA and other less potent retinoids in the treatment of aging skin without the detrimental side effects.