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

doi:10.1016/j.redox.2020.101790

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

Redox Biol. 2021 Jan:38:101790. doi: 10.1016/j.redox.2020.101790. Epub 2020 Nov 6.

Authors

Affiliations

¹ Department of Anatomy and Histology, School of Medical Sciences, University of Sydney, Australia; Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia.
² St. George and Sutherland Clinical School, University of New South Wales, Sydney, Australia.
³ 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.
⁴ Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia.
⁵ Department of Pathology, Faculty of Medicine and Health, University of Sydney, Australia.
⁶ Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, Australia.
⁷ Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
⁸ School of Life Sciences, University of Technology, Sydney, Australia.
⁹ School of Medical Sciences, University of New South Wales, Sydney, Australia.
¹⁰ Biological Resources Imaging Laboratory, University of New South Wales, Sydney, Australia.
¹¹ Bosch Institute, Faculty of Medicine and Health, University of Sydney, Australia; Department of Physiology, School of Medical Sciences, University of Sydney, Australia.
¹² St. George and Sutherland Clinical School, University of New South Wales, Sydney, Australia. Electronic address: abhirupdas@unsw.edu.au.

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.

Keywords: Anti-inflammatory; Geroprotection; Immunomodulation; SOD mimetic; Skin regeneration; UV protection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Epidermis
Mice
Skin Neoplasms*
Skin*
Superoxide Dismutase
Tetradecanoylphorbol Acetate

Substances

Superoxide Dismutase
Tetradecanoylphorbol Acetate