Effects of topical copper tripeptide complex on wound healing in an irradiated rat model.

Abstract

OBJECTIVES:

To evaluate clinical and immunohistopathological effects of topical glycyl-histidyl-lysine-copper (GHK-Cu) on in vivo irradiated rat wounds.

DESIGN:

Animal model.

SETTING:

Academic institution.

SUBJECTS AND 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: Noah P Parker, Farhad Ardeshirpour, Stephen C Schmechel, Amy Anne D Lassig
• Journal: Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery (Otolaryngol Head Neck Surg) Vol. 149 Issue 3 Pg. 384-9 (Sep 2013) ISSN: 1097-6817 [Electronic] England
• PMID: 23744835 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caveolin 1
• Oligopeptides
• Vascular Endothelial Growth Factor A
• glycyl-histidyl-lysine
• Copper

Topics

• Administration, Topical
• Animals
• Caveolin 1 (metabolism)
• Copper (administration & dosage, pharmacology)
• Immunohistochemistry
• Male
• Oligopeptides (administration & dosage, pharmacology)
• Radiation Injuries (drug therapy)
• Rats
• Rats, Sprague-Dawley
• Surgical Flaps
• Vascular Endothelial Growth Factor A (metabolism)
• Wound Healing (drug effects, radiation effects)