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MnSOD is implicated in accelerated wound healing upon Negative Pressure Wound Therapy (NPWT): A case in point for MnSOD mimetics as adjuvants for wound management.

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Date
2019-01
Authors
Bellot, Gregory Lucien
Dong, Xiaoke
Lahiri, Amitabha
Sebastin, Sandeep Jacob
Batinic-Haberle, Ines
Pervaiz, Shazib
Puhaindran, Mark Edward
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Abstract
Negative Pressure Wound Therapy (NPWT), a widely used modality in the management of surgical and trauma wounds, offers clear benefits over conventional wound healing strategies. Despite the wide-ranging effects ascribed to NPWT, the precise molecular mechanisms underlying the accelerated healing supported by NPWT remains poorly understood. Notably, cellular redox status-a product of the balance between cellular reactive oxygen species (ROS) production and anti-oxidant defense systems-plays an important role in wound healing and dysregulation of redox homeostasis has a profound effect on wound healing. Here we investigated potential links between the use of NPWT and the regulation of antioxidant mechanisms. Using patient samples and a rodent model of acute injury, we observed a significant accumulation of MnSOD protein as well as higher enzymatic activity in tissues upon NPWT. As a proof of concept and to outline the important role of SOD activity in wound healing, we replaced NPWT by the topical application of a MnSOD mimetic, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+, MnE, BMX-010, AEOl10113) in the rodent model. We observed that MnE is a potent wound healing enhancer as it appears to facilitate the formation of new tissue within the wound bed and consequently advances wound closure by two days, compared to the non-treated animals. Taken together, these results show for the first time a link between NPWT and regulation of antioxidant mechanism through the maintenance of MnSOD activity. Additionally this discovery outlined the potential role of MnSOD mimetics as topical agents enhancing wound healing.
Type
Journal article
Subject
Animals
Humans
Rats
Disease Models, Animal
Metalloporphyrins
Superoxide Dismutase
Antioxidants
Treatment Outcome
Combined Modality Therapy
Administration, Topical
Biomimetics
Wound Healing
Enzyme Activation
Disease Management
Negative-Pressure Wound Therapy
Biological Mimicry
Permalink
https://hdl.handle.net/10161/21189
Published Version (Please cite this version)
10.1016/j.redox.2018.10.014
Publication Info
Bellot, Gregory Lucien; Dong, Xiaoke; Lahiri, Amitabha; Sebastin, Sandeep Jacob; Batinic-Haberle, Ines; Pervaiz, Shazib; & Puhaindran, Mark Edward (2019). MnSOD is implicated in accelerated wound healing upon Negative Pressure Wound Therapy (NPWT): A case in point for MnSOD mimetics as adjuvants for wound management. Redox biology, 20. pp. 307-320. 10.1016/j.redox.2018.10.014. Retrieved from https://hdl.handle.net/10161/21189.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Batinic-Haberle

Ines Batinic-Haberle

Professor Emeritus of Radiation Oncology
            A major interest of mine has been in the design and synthesis of Mn porphyrin(MnP)-based powerful catalytic antioxidants which helped establish structure-activity relationship (SAR). It relates the redox property of metalloporphyrins to their ability to remove superoxide. SAR has facilitated the design of redox-active therapeutics and served as a tool for mechanistic considerations. Importantly SAR parallels the magnitu
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