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Skin protective effects of RM191A, a novel superoxide dismutase mimetic

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

Posted 11 May 2020
bioRxiv DOI: 10.1101/2020.05.10.086694

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 (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. ### Competing Interest Statement LC is the Director and co-founder of RR MedSciences that holds patents for the synthesis and application of RM191A. Research studies at Macquarie University, University of New South Wales and University of Sydney were funded by RR MedSciences.

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