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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
12 Downloads (Pure)

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 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.

Original languageEnglish
Article number101790
Pages (from-to)1-13
Number of pages13
JournalRedox Biology
Volume38
DOIs
Publication statusPublished - 1 Jan 2021

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Anti-inflammatory
  • Geroprotection
  • Immunomodulation
  • Skin regeneration
  • SOD mimetic
  • UV protection

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