Skin protective and regenerative effects of RM191A, a novel superoxide dismutase mimetic

Shariev, Artur; Menounos, Spiro; Laos, Alistair J.; Laxman, Pooja; Lai, Donna; Hua, Sheng; Zinger, Anna; McRae, Christopher R.; Casbolt, Llewellyn S.; Combes, Valery; Smith, Greg; Hung, Tzong-tyng; Dixon, Katie M.; Thordarson, Pall; Mason, Rebecca S.; Das, Abhirup

Superoxide 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 (Cu(2+)-Cu(3+))-centred polyglycine coordination complex. It displays 10-fold higher superoxide quenching activity compared to SOD as well as significant antioxidant, anti-inflammatory and immunomodulatory activities through beneficial modulation of several significant inflammatory cytokines in vitro and in vivo. 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 non-toxic, non-teratogenic and readily distributed in the body of mice. Moreover, it significantly accelerates excisional wound healing, reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation and attenuates age-associated oxidative stress in skin, demonstrating both skin regenerative and geroprotective properties of RM191A.