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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	101790
Pages (from-to)	1-13
Number of pages	13
Journal	Redox Biology
Volume	38
DOIs	https://doi.org/10.1016/j.redox.2020.101790
Publication status	Published - 1 Jan 2021

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

Anti-inflammatory
Geroprotection
Immunomodulation
Skin regeneration
SOD mimetic
UV protection

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10.1016/j.redox.2020.101790Licence: CC BY-NC-ND

Publisher version (open access)Final published version, 7.13 MBLicence: CC BY-NC-ND

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Shariev, A., Menounos, S., Laos, A. J., Laxman, P., Lai, D., Hua, S., Zinger, A., McRae, C. R., Casbolt, L. S., Combes, V., Smith, G., Hung, T., Dixon, K. M., Thordarson, P., Mason, R. S., & Das, A. (2021). Skin protective and regenerative effects of RM191A, a novel superoxide dismutase mimetic. Redox Biology, 38, 1-13. Article 101790. https://doi.org/10.1016/j.redox.2020.101790

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

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, Skin regeneration, SOD mimetic, UV protection",

author = "Artur Shariev and Spiro Menounos and Laos, \{Alistair J.\} and Pooja Laxman and Donna Lai and Sheng Hua and Anna Zinger and McRae, \{Christopher R.\} and Casbolt, \{Llewellyn S.\} and Valery Combes and Greg Smith and Tzong-tyng Hung and Dixon, \{Katie M.\} and Pall Thordarson and Mason, \{Rebecca S.\} and Abhirup Das",

note = "Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2021",

month = jan,

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doi = "10.1016/j.redox.2020.101790",

language = "English",

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T1 - Skin protective and regenerative effects of RM191A, a novel superoxide dismutase mimetic

AU - Shariev, Artur

AU - Menounos, Spiro

AU - Laos, Alistair J.

AU - Laxman, Pooja

AU - Lai, Donna

AU - Hua, Sheng

AU - Zinger, Anna

AU - McRae, Christopher R.

AU - Casbolt, Llewellyn S.

AU - Combes, Valery

AU - Smith, Greg

AU - Hung, Tzong-tyng

AU - Dixon, Katie M.

AU - Thordarson, Pall

AU - Mason, Rebecca S.

AU - Das, Abhirup

N1 - Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - 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.

AB - 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.

KW - Anti-inflammatory

KW - Geroprotection

KW - Immunomodulation

KW - Skin regeneration

KW - SOD mimetic

KW - UV protection

UR - https://www.scopus.com/pages/publications/85096130281

U2 - 10.1016/j.redox.2020.101790

DO - 10.1016/j.redox.2020.101790

M3 - Article

C2 - 33202300

AN - SCOPUS:85096130281

SN - 2213-2317

VL - 38

SP - 1

EP - 13

JO - Redox Biology

JF - Redox Biology

M1 - 101790

ER -

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

Abstract

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Keywords

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