title: Effects of topical copper tripeptide complex on wound healing in an irradiated rat model.
abstract: OBJECTIVE
  To evaluate clinical and immunohistopathological effects of topical glycyl-histidyl-lysine-copper (GHK-Cu) on in vivo irradiated rat wounds.
  
  
  METHODS
  Animal model.
  
  
  METHODS
  Academic institution.
  
  
  METHODS
  After dorsal irradiation and a 28-day recovery period, 2 × 8 cm cranially based dorsal flaps were created in Sprague-Dawley rats. Twice daily GHK-Cu gel (test) or aquaphilic ointment (control) was applied for 10 days. Animals were euthanized, digital images of flaps were taken, and harvested tissues were immunohistochemically stained for a vascular endothelium marker, caveolin-1, and vascular endothelial growth factor (VEGF). Digital image analysis was used for outcome measures. Unpaired t-tests were used for statistical analyses; significance of P < .01 accounted for multiple comparisons.
  
  
  RESULTS
  By digital analysis of clinical images, 13 test and 10 control animals showed mean ischemic areas of 5.0 cm(2) (SD = 0.9) for tests and 3.8 cm(2) (SD = 1.1; P = .011) for controls. Whole slide digitized images allowed quantification of caveolin-1-stained blood vessels and VEGF expression in fibroblasts at the interface of healing flaps. Caveolin-1 analyses showed a mean of 209.0 vessels (SD = 111.1) and a mean vessel luminal area of 525.7 um(2) (SD = 191.0) in tests and 207.4 vessels (SD = 109.4; P = .973) and 422.8 um(2) (SD = 109.7; P = .118) in controls. VEGF quantified as the percentage of pixels exceeding a colorimetric threshold, with higher fractions of positive pixels indicating more intense staining, showed a mean intensity score of 0.34 (SD = 0.19) in tests and 0.54 (SD = 0.41; P = .169) in controls.
  
  
  CONCLUSIONS
  Irradiated dorsal rat flaps treated with topical GHK-Cu gel demonstrated no difference in flap ischemia, blood vessel number or area, or VEGF expression compared to controls.
authors.affiliation: Departments of Otolaryngology-Head and Neck Surgery, University of Minnesota Medical Center, Minneapolis, Minnesota 55455, USA. noahpparker@gmail.com
authors.forename: Noah P
authors.initials: NP
authors.lastname: Parker
authors.forename: Farhad
authors.initials: F
authors.lastname: Ardeshirpour
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Schmechel
authors.forename: Amy Anne D
authors.initials: AA
authors.lastname: Lassig
mesh_terms: D000287:Administration, Topical; D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D003300:Copper / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D011832:Radiation Injuries / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013524:Surgical Flaps; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000528:radiation effects
chemical_list: D051242:Caveolin 1; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; C020905:glycyl-histidyl-lysine; D003300:Copper
keywords: animal model; copper tripeptide; irradiation; radiation; rat; wound healing