Skin protective effects of RM191A, a novel superoxide dismutase mimetic

Shariev, A.; Laos, A. J.; Lai, D.; Hua, S.; Zinger, A.; Mcrae, C. R.; Casbolt, L. S.; Combes, V.; Hung, T.-t.; Dixon, K. M.; Thordarson, P.; Mason, R. S.; Das, A.

doi:10.1101/2020.05.10.086694

bioRxiv · 10.1101/2020.05.10.086694

Skin protective effects of RM191A, a novel superoxide dismutase mimetic

Shariev, A.·Laos, A. J.·Lai, D.·Hua, S.·Zinger, A.·Mcrae, C. R.·Casbolt, L. S.·Combes, V.·Hung, T.-t.·Dixon, K. M.·Thordarson, P.·Mason, R. S.·Das, A.

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Abstract

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. HighlightsO_LISuperoxide dismutase mimetic RM191A is a highly stable copper (Cu2+-Cu3+)-polyglycine coordination complex C_LIO_LIRM191A exhibits potent antioxidant (10-fold more than that of superoxide dismutase) properties in vitro C_LIO_LIRM191A exhibits potent anti-inflammatory properties in vitro and in vivo C_LIO_LIRM191A protects human skin explants against UV-induced oxidative stress and DNA damage C_LIO_LIRM191A is non-toxic and readily bioavailable in mice C_LIO_LIRM191A attenuates TPA-induced skin inflammation and improves wound healing in mice C_LI

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Shariev, A., Laos, A. J., Lai, D., Hua, S., Zinger, A., Mcrae, C. R., Casbolt, L. S., Combes, V., Hung, T.-t., Dixon, K. M., Thordarson, P., Mason, R. S., Das, A.. 2020-05-11. Skin protective effects of RM191A, a novel superoxide dismutase mimetic. https://doi.org/10.1101/2020.05.10.086694

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