The Beta 2 Adrenergic Receptor Antagonist Timolol Improves Healing of Combined Burn and Radiation Wounds

Huguette Albrecht, Hsin Ya Yang, Maija Ht Kiuru, Saipiroon Maksaereekul, Blythe Durbin-Johnson, Michael S Wong, Thomas R Stevenson, David M Rocke, Roslyn Rivkah Isseroff

Research output: Contribution to journalArticle

Abstract

In a scenario involving a nuclear detonation during war or a terrorist attack, acute radiation exposure combined with thermal and blast effects results in severe skin injury. Although the cutaneous injury in such a scenario may not be lethal, it may lead to inflammation, delayed wound healing and loss of the skin barrier, resulting in an increased risk of infection. In this study, we tested the potential use of timolol, a beta-adrenergic receptor antagonist, to improve epidermal wound closure after combined burn and radiation injury using an ex vivo human skin culture model. Daily application of 10 μM timolol after combined injury (burn and 10 Gy ex vivo irradiation) increased wound epithelialization by 5-20%. In addition, exposure to 10 Gy significantly suppressed epidermal keratinocyte proliferation by 46% at 48 h postirradiation. Similar to what has been observed in a thermal burn injury, the enzyme phenylethanolamine N-methyltransferase (PNMT), which generates epinephrine, was elevated in the combined thermal burn and radiation wounds. This likely resulted in elevated tissue levels of this catecholamine, which has been shown to delay healing. Thus, with the addition of timolol to the wound to block the binding of locally generated epinephrine to the beta-adrenergic receptor, healing is improved. This work suggests that by antagonizing local epinephrine action within the wound, a beta-adrenergic receptor antagonist such as timolol may be a useful adjunctive treatment to improve healing in the combined burn and radiation injury.

Original languageEnglish (US)
Pages (from-to)441-445
Number of pages5
JournalRadiation Research
Volume189
Issue number4
DOIs
StatePublished - Apr 1 2018

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'The Beta 2 Adrenergic Receptor Antagonist Timolol Improves Healing of Combined Burn and Radiation Wounds'. Together they form a unique fingerprint.

  • Cite this