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. and Mattson, Mark P. (2010) A synthetic uric acid analog accelerates cutaneous wound healing in mice. Plos One, 5 4: e10044-1-e10044 -10. doi: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.
Title A synthetic uric acid analog accelerates cutaneous wound healing in mice
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2010-04
Year available 2010
Sub-type Article (original research)
DOI 10.1371/journal.pone.0010044
Open Access Status DOI
Volume 5
Issue 4
Start page e10044-1
End page e10044 -10
Total pages 10
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2011
Language eng
Abstract 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. Copyright © 2011 Elsevier B.V. All rights reserved.
Keyword Pharmacology
Dermatology (Human Medicine, Medical Sciences)
fibroblast/vascular endothelial cell
Circulatory System
Integumentary system
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article Number: e10044. 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.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
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Created: Wed, 14 Jul 2010, 11:44:24 EST by Bacsweet Kaur on behalf of School of Biomedical Sciences