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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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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. |
format | Online Article Text |
id | pubmed-4284939 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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