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

4 Citations (Scopus)

32 Downloads (Pure)

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

Cite this

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. [101790]. https://doi.org/10.1016/j.redox.2020.101790

Shariev, Artur ; Menounos, Spiro ; Laos, Alistair J. ; Laxman, Pooja ; Lai, Donna ; Hua, Sheng ; Zinger, Anna ; McRae, Christopher R. ; Casbolt, Llewellyn S. ; Combes, Valery ; Smith, Greg ; Hung, Tzong-tyng ; Dixon, Katie M. ; Thordarson, Pall ; Mason, Rebecca S. ; Das, Abhirup. / Skin protective and regenerative effects of RM191A, a novel superoxide dismutase mimetic. In: Redox Biology. 2021 ; Vol. 38. pp. 1-13.

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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,

day = "1",

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

language = "English",

volume = "38",

pages = "1--13",

journal = "Redox Biology",

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Skin protective and regenerative effects of RM191A, a novel superoxide dismutase mimetic. / Shariev, Artur; Menounos, Spiro; Laos, Alistair J.; Laxman, Pooja; Lai, Donna; Hua, Sheng; Zinger, Anna; McRae, Christopher R.; Casbolt, Llewellyn S.; Combes, Valery; Smith, Greg; Hung, Tzong-tyng; Dixon, Katie M.; Thordarson, Pall; Mason, Rebecca S.; Das, Abhirup.

In: Redox Biology, Vol. 38, 101790, 01.01.2021, p. 1-13.

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

TY - JOUR

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

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U2 - 10.1016/j.redox.2020.101790

DO - 10.1016/j.redox.2020.101790

M3 - Article

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AN - SCOPUS:85096130281

VL - 38

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JO - Redox Biology

JF - Redox Biology

SN - 2213-2317

M1 - 101790

ER -

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

Abstract

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