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Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox Parameters

By 2025, more than 500 M people worldwide will suffer from diabetes; 125 M will develop foot ulcer(s) and 20 M will undergo an amputation, creating a major health problem. Understanding how these wounds become chronic will provide insights to reverse chronicity. We hypothesized that oxidative stress...

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Autores principales: Dhall, Sandeep, Do, Danh C., Garcia, Monika, Kim, Jane, Mirebrahim, Seyed H., Lyubovitsky, Julia, Lonardi, Stefano, Nothnagel, Eugene A., Schiller, Neal, Martins-Green, Manuela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284939/
https://www.ncbi.nlm.nih.gov/pubmed/25587545
http://dx.doi.org/10.1155/2014/562625
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author Dhall, Sandeep
Do, Danh C.
Garcia, Monika
Kim, Jane
Mirebrahim, Seyed H.
Lyubovitsky, Julia
Lonardi, Stefano
Nothnagel, Eugene A.
Schiller, Neal
Martins-Green, Manuela
author_facet Dhall, Sandeep
Do, Danh C.
Garcia, Monika
Kim, Jane
Mirebrahim, Seyed H.
Lyubovitsky, Julia
Lonardi, Stefano
Nothnagel, Eugene A.
Schiller, Neal
Martins-Green, Manuela
author_sort Dhall, Sandeep
collection PubMed
description By 2025, more than 500 M people worldwide will suffer from diabetes; 125 M will develop foot ulcer(s) and 20 M will undergo an amputation, creating a major health problem. Understanding how these wounds become chronic will provide insights to reverse chronicity. We hypothesized that oxidative stress (OS) in wounds is a critical component for generation of chronicity. We used the db/db mouse model of impaired healing and inhibited, at time of injury, two major antioxidant enzymes, catalase and glutathione peroxidase, creating high OS in the wounds. This was necessary and sufficient to trigger wounds to become chronic. The wounds initially contained a polymicrobial community that with time selected for specific biofilm-forming bacteria. To reverse chronicity we treated the wounds with the antioxidants α-tocopherol and N-acetylcysteine and found that OS was highly reduced, biofilms had increased sensitivity to antibiotics, and granulation tissue was formed with proper collagen deposition and remodeling. We show for the first time generation of chronic wounds in which biofilm develops spontaneously, illustrating importance of early and continued redox imbalance coupled with the presence of biofilm in development of wound chronicity. This model will help decipher additional mechanisms and potentially better diagnosis of chronicity and treatment of human chronic wounds.
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spelling pubmed-42849392015-01-13 Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox Parameters Dhall, Sandeep Do, Danh C. Garcia, Monika Kim, Jane Mirebrahim, Seyed H. Lyubovitsky, Julia Lonardi, Stefano Nothnagel, Eugene A. Schiller, Neal Martins-Green, Manuela J Diabetes Res Research Article By 2025, more than 500 M people worldwide will suffer from diabetes; 125 M will develop foot ulcer(s) and 20 M will undergo an amputation, creating a major health problem. Understanding how these wounds become chronic will provide insights to reverse chronicity. We hypothesized that oxidative stress (OS) in wounds is a critical component for generation of chronicity. We used the db/db mouse model of impaired healing and inhibited, at time of injury, two major antioxidant enzymes, catalase and glutathione peroxidase, creating high OS in the wounds. This was necessary and sufficient to trigger wounds to become chronic. The wounds initially contained a polymicrobial community that with time selected for specific biofilm-forming bacteria. To reverse chronicity we treated the wounds with the antioxidants α-tocopherol and N-acetylcysteine and found that OS was highly reduced, biofilms had increased sensitivity to antibiotics, and granulation tissue was formed with proper collagen deposition and remodeling. We show for the first time generation of chronic wounds in which biofilm develops spontaneously, illustrating importance of early and continued redox imbalance coupled with the presence of biofilm in development of wound chronicity. This model will help decipher additional mechanisms and potentially better diagnosis of chronicity and treatment of human chronic wounds. Hindawi Publishing Corporation 2014 2014-12-23 /pmc/articles/PMC4284939/ /pubmed/25587545 http://dx.doi.org/10.1155/2014/562625 Text en Copyright © 2014 Sandeep Dhall et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Dhall, Sandeep
Do, Danh C.
Garcia, Monika
Kim, Jane
Mirebrahim, Seyed H.
Lyubovitsky, Julia
Lonardi, Stefano
Nothnagel, Eugene A.
Schiller, Neal
Martins-Green, Manuela
Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox Parameters
title Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox Parameters
title_full Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox Parameters
title_fullStr Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox Parameters
title_full_unstemmed Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox Parameters
title_short Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox Parameters
title_sort generating and reversing chronic wounds in diabetic mice by manipulating wound redox parameters
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284939/
https://www.ncbi.nlm.nih.gov/pubmed/25587545
http://dx.doi.org/10.1155/2014/562625
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