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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.
Affiliation
  • Shariev A; Department of Anatomy and Histology, School of Medical Sciences, University of Sydney, Australia; Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia.
  • Menounos S; St. George and Sutherland Clinical School, University of New South Wales, Sydney, Australia.
  • Laos AJ; School of Chemistry, The Australian Centre for Nanomedicine and the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of New South Wales, Sydney, Australia.
  • Laxman P; School of Chemistry, The Australian Centre for Nanomedicine and the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of New South Wales, Sydney, Australia.
  • Lai D; Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia.
  • Hua S; Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia.
  • Zinger A; Department of Pathology, Faculty of Medicine and Health, University of Sydney, Australia.
  • McRae CR; Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, Australia.
  • Casbolt LS; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
  • Combes V; School of Life Sciences, University of Technology, Sydney, Australia.
  • Smith G; School of Medical Sciences, University of New South Wales, Sydney, Australia.
  • Hung TT; Biological Resources Imaging Laboratory, University of New South Wales, Sydney, Australia.
  • Dixon KM; Department of Anatomy and Histology, School of Medical Sciences, University of Sydney, Australia; Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia.
  • Thordarson P; School of Chemistry, The Australian Centre for Nanomedicine and the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of New South Wales, Sydney, Australia.
  • Mason RS; Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia; Department of Physiology, School of Medical Sciences, University of Sydney, Australia.
  • Das A; St. George and Sutherland Clinical School, University of New South Wales, Sydney, Australia. Electronic address: abhirupdas@unsw.edu.au.
Redox Biol ; 38: 101790, 2021 01.
Article in En | MEDLINE | ID: mdl-33202300
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.
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Full text: 1 Database: MEDLINE Main subject: Skin / Skin Neoplasms Limits: Animals Language: En Journal: Redox Biol Year: 2021 Type: Article Affiliation country: Australia
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Full text: 1 Database: MEDLINE Main subject: Skin / Skin Neoplasms Limits: Animals Language: En Journal: Redox Biol Year: 2021 Type: Article Affiliation country: Australia