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A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice
Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2850366/ https://www.ncbi.nlm.nih.gov/pubmed/20386608 http://dx.doi.org/10.1371/journal.pone.0010044 |
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author | Chigurupati, Srinivasulu Mughal, Mohamed R. Chan, Sic L. Arumugam, Thiruma V. Baharani, Akanksha Tang, Sung-Chun Yu, Qian-Sheng Holloway, Harold W. Wheeler, Ross Poosala, Suresh Greig, Nigel H. Mattson, Mark P. |
author_facet | Chigurupati, Srinivasulu Mughal, Mohamed R. Chan, Sic L. Arumugam, Thiruma V. Baharani, Akanksha Tang, Sung-Chun Yu, Qian-Sheng Holloway, Harold W. Wheeler, Ross Poosala, Suresh Greig, Nigel H. Mattson, Mark P. |
author_sort | Chigurupati, Srinivasulu |
collection | PubMed |
description | Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions. |
format | Text |
id | pubmed-2850366 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28503662010-04-12 A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice Chigurupati, Srinivasulu Mughal, Mohamed R. Chan, Sic L. Arumugam, Thiruma V. Baharani, Akanksha Tang, Sung-Chun Yu, Qian-Sheng Holloway, Harold W. Wheeler, Ross Poosala, Suresh Greig, Nigel H. Mattson, Mark P. PLoS One Research Article Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions. Public Library of Science 2010-04-06 /pmc/articles/PMC2850366/ /pubmed/20386608 http://dx.doi.org/10.1371/journal.pone.0010044 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Chigurupati, Srinivasulu Mughal, Mohamed R. Chan, Sic L. Arumugam, Thiruma V. Baharani, Akanksha Tang, Sung-Chun Yu, Qian-Sheng Holloway, Harold W. Wheeler, Ross Poosala, Suresh Greig, Nigel H. Mattson, Mark P. A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice |
title | A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice |
title_full | A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice |
title_fullStr | A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice |
title_full_unstemmed | A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice |
title_short | A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice |
title_sort | synthetic uric acid analog accelerates cutaneous wound healing in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2850366/ https://www.ncbi.nlm.nih.gov/pubmed/20386608 http://dx.doi.org/10.1371/journal.pone.0010044 |
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