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

Redox Biology (Jan 2021)

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.

Journal volume & issue: Vol. 38
p. 101790

Abstract

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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.

Published in Redox Biology

ISSN: 2213-2317 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.journals.elsevier.com/redox-biology/

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