A synthetic uric acid analog accelerates cutaneous wound healing in mice

Srinivasulu Chigurupati, Mohamed R. Mughal, Sic L. Chan, Thiruma V. Arumugam, Akanksha Baharani, Sung Chun Tang, Qian Sheng Yu, Harold W. Holloway, Ross Wheeler, Suresh Poosala, Nigel H. Greig, Mark P. Mattson

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere10044
JournalPLoS One
Volume5
Issue number4
DOIs
StatePublished - 2010

Fingerprint

uric acid
Uric Acid
tissue repair
Wound Healing
Skin
mice
Oxidative stress
Tissue
animal injuries
Solubility
solubility
Wounds and Injuries
Oxidative Stress
oxidative stress
Antioxidants
wound treatment
Free Radical Scavengers
Aptitude
Macrophages
free radical scavengers

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Chigurupati, S., Mughal, M. R., Chan, S. L., Arumugam, T. V., Baharani, A., Tang, S. C., ... Mattson, M. P. (2010). A synthetic uric acid analog accelerates cutaneous wound healing in mice. PLoS One, 5(4), [e10044]. https://doi.org/10.1371/journal.pone.0010044

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.

In: PLoS One, Vol. 5, No. 4, e10044, 2010.

Research output: Contribution to journalArticle

Chigurupati, S, Mughal, MR, Chan, SL, Arumugam, TV, Baharani, A, Tang, SC, Yu, QS, Holloway, HW, Wheeler, R, Poosala, S, Greig, NH & Mattson, MP 2010, 'A synthetic uric acid analog accelerates cutaneous wound healing in mice', PLoS One, vol. 5, no. 4, e10044. https://doi.org/10.1371/journal.pone.0010044
Chigurupati S, Mughal MR, Chan SL, Arumugam TV, Baharani A, Tang SC et al. A synthetic uric acid analog accelerates cutaneous wound healing in mice. PLoS One. 2010;5(4). e10044. https://doi.org/10.1371/journal.pone.0010044
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. In: PLoS One. 2010 ; Vol. 5, No. 4.
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