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
Affiliations
Artur Shariev
Department of Anatomy and Histology, School of Medical Sciences, University of Sydney, Australia; Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia
Spiro Menounos
St. George and Sutherland Clinical School, University of New South Wales, Sydney, Australia
Alistair J. Laos
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
Pooja Laxman
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
Donna Lai
Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia
Sheng Hua
Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia
Anna Zinger
Department of Pathology, Faculty of Medicine and Health, University of Sydney, Australia
Christopher R. McRae
Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, Australia
Llewellyn S. Casbolt
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia
Valery Combes
School of Life Sciences, University of Technology, Sydney, Australia
Greg Smith
School of Medical Sciences, University of New South Wales, Sydney, Australia
Tzong-tyng Hung
Biological Resources Imaging Laboratory, University of New South Wales, Sydney, Australia
Katie M. Dixon
Department of Anatomy and Histology, School of Medical Sciences, University of Sydney, Australia; Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia
Pall Thordarson
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
Rebecca S. Mason
Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia; Department of Physiology, School of Medical Sciences, University of Sydney, Australia
Abhirup Das
St. George and Sutherland Clinical School, University of New South Wales, Sydney, Australia; Corresponding author.
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.
