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

Shariev, A; Menounos, S; Laos, AJ; Laxman, P; Lai, D; Hua, S; Zinger, A; McRae, CR; Casbolt, LS; Combes, V; Smith, G; Hung, T-T; Dixon, KM; Thordarson, P; Mason, RS; Das, A

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

Shariev, A Menounos, S Laos, AJ Laxman, P Lai, D Hua, S Zinger, A McRae, CR Casbolt, LS Combes, V

Smith, G Hung, T-T Dixon, KM Thordarson, P Mason, RS Das, A

Permalink

Publisher:: Elsevier BV
Publication Type:: Journal Article
Citation:: Redox Biol, 2021, 38, pp. 101790
Issue Date:: 2021-01

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download full textAdobe PDF (7.31 MB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Shariev, A
dc.contributor.author	Menounos, S
dc.contributor.author	Laos, AJ
dc.contributor.author	Laxman, P
dc.contributor.author	Lai, D
dc.contributor.author	Hua, S
dc.contributor.author	Zinger, A
dc.contributor.author	McRae, CR
dc.contributor.author	Casbolt, LS
dc.contributor.author	Combes, V https://orcid.org/0000-0003-2178-3596
dc.contributor.author	Smith, G
dc.contributor.author	Hung, T-T
dc.contributor.author	Dixon, KM
dc.contributor.author	Thordarson, P
dc.contributor.author	Mason, RS
dc.contributor.author	Das, A
dc.date.accessioned	2022-01-14T05:52:29Z
dc.date.available	2020-11-02
dc.date.available	2022-01-14T05:52:29Z
dc.date.issued	2021-01
dc.identifier.citation	Redox Biol, 2021, 38, pp. 101790
dc.identifier.issn	2213-2317
dc.identifier.issn	2213-2317
dc.identifier.uri	http://hdl.handle.net/10453/153126
dc.description.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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Elsevier BV
dc.relation.ispartof	Redox Biol
dc.relation.isbasedon	10.1016/j.redox.2020.101790
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 1101 Medical Biochemistry and Metabolomics, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.mesh	Animals
dc.subject.mesh	Epidermis
dc.subject.mesh	Mice
dc.subject.mesh	Skin
dc.subject.mesh	Skin Neoplasms
dc.subject.mesh	Superoxide Dismutase
dc.subject.mesh	Tetradecanoylphorbol Acetate
dc.subject.mesh	Epidermis
dc.subject.mesh	Skin
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Skin Neoplasms
dc.subject.mesh	Tetradecanoylphorbol Acetate
dc.subject.mesh	Superoxide Dismutase
dc.title	Skin protective and regenerative effects of RM191A, a novel superoxide dismutase mimetic.
dc.type	Journal Article
utslib.citation.volume	38
utslib.location.activity	Netherlands
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1101 Medical Biochemistry and Metabolomics
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2022-01-14T05:52:23Z
pubs.publication-status	Published
pubs.volume	38

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/153126