Title

A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice

Authors

Authors

S. Chigurupati; M. R. Mughal; S. L. Chan; T. V. Arumugam; A. Baharani; S. C. Tang; Q. S. Yu; H. W. Holloway; R. Wheeler; S. Poosala; N. H. Greig;M. P. Mattson

Comments

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Abbreviated Journal Title

PLoS One

Keywords

ISCHEMIC BRAIN-INJURY; DIABETIC FOOT ULCERS; OXIDATIVE STRESS; GROWTH-FACTOR; ANTIOXIDANT DEFENSE; NITRIC-OXIDE; REPAIR; ANGIOGENESIS; PATHOGENESIS; GLUTATHIONE; Multidisciplinary Sciences

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.

Journal Title

Plos One

Volume

5

Issue/Number

3

Publication Date

1-1-2010

Document Type

Article

Language

English

First Page

10

WOS Identifier

WOS:000276420400015

ISSN

1932-6203

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