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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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2014/562625 |
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| author | Sandeep Dhall Danh C. Do Monika Garcia Jane Kim Seyed H. Mirebrahim Julia Lyubovitsky Stefano Lonardi Eugene A. Nothnagel Neal Schiller Manuela Martins-Green |
| author_facet | Sandeep Dhall Danh C. Do Monika Garcia Jane Kim Seyed H. Mirebrahim Julia Lyubovitsky Stefano Lonardi Eugene A. Nothnagel Neal Schiller Manuela Martins-Green |
| author_sort | Sandeep Dhall |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-dd5e61ed62694b9fa448ea5bd760861a |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-dd5e61ed62694b9fa448ea5bd760861a2025-08-20T03:26:30ZengWileyJournal of Diabetes Research2314-67452314-67532014-01-01201410.1155/2014/562625562625Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox ParametersSandeep Dhall0Danh C. Do1Monika Garcia2Jane Kim3Seyed H. Mirebrahim4Julia Lyubovitsky5Stefano Lonardi6Eugene A. Nothnagel7Neal Schiller8Manuela Martins-Green9Department of Cell Biology and Neuroscience, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USADivision of Biomedical Sciences, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USADepartment of Cell Biology and Neuroscience, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USADepartment of Botany and Plant Sciences, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USADepartment of Computer Science and Engineering, University of California, Riverside, Riverside, CA 92521, USABioengineering Interdepartmental Graduate Program, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USADepartment of Computer Science and Engineering, University of California, Riverside, Riverside, CA 92521, USADepartment of Botany and Plant Sciences, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USADivision of Biomedical Sciences, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USADepartment of Cell Biology and Neuroscience, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USABy 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.http://dx.doi.org/10.1155/2014/562625 |
| spellingShingle | Sandeep Dhall Danh C. Do Monika Garcia Jane Kim Seyed H. Mirebrahim Julia Lyubovitsky Stefano Lonardi Eugene A. Nothnagel Neal Schiller Manuela Martins-Green Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox Parameters Journal of Diabetes Research |
| 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 |
| url | http://dx.doi.org/10.1155/2014/562625 |
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