Skin protective effects of RM191A, a novel superoxide dismutase mimetic

Abstract

AbstractSuperoxide dismutase (SOD) is known to be protective against oxidative stress-mediated skin dysfunction. Here we explore the potential therapeutic activities of RM191A, a novel SOD mimetic, on skin. RM191A is a water soluble, dimeric copper (Cu2+-Cu3+)-centred polyglycine coordination complex. It displays 10-fold higher superoxide quenching activity compared to SOD as well as significant anti-inflammatory activity through beneficial modulation of several significant inflammatory pathways in cells.We tested the therapeutic potential of RM191A in a topical gel using a human skin explant model and observed that it significantly inhibits UV-induced DNA damage in the epidermis and dermis, including cyclobutane pyrimidine dimers (CPD), 8-oxo-guanine (8-oxoG) and 8-nitroguanine (8NGO). RM191A topical gel is found to be safe and non-toxic in mice following month-long daily dosing at 0.19 mL/kg body weight. Moreover, it significantly accelerates excisional wound healing, and reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice.HighlightsSuperoxide dismutase mimetic RM191A is a highly stable copper (Cu2+-Cu3+)-polyglycine coordination complexRM191A exhibits potent antioxidant (10-fold more than that of superoxide dismutase) properties in vitroRM191A exhibits potent anti-inflammatory properties in vitro and in vivoRM191A protects human skin explants against UV-induced oxidative stress and DNA damageRM191A is non-toxic and readily bioavailable in miceRM191A attenuates TPA-induced skin inflammation and improves wound healing in mice