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Glu-Trp-ONa or its acylated analogue (R-Glu-Trp-ONa) administration enhances the wound healing in the model of chronic skin wounds in rabbits

Authors Shevtsov M, Smagina L, Kudriavtceva T, Petlenko S, Voronkina I

Received 21 December 2014

Accepted for publication 29 January 2015

Published 20 March 2015 Volume 2015:9 Pages 1717—1727

DOI https://doi.org/10.2147/DDDT.S79665

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 6

Editor who approved publication: Professor Shu-Feng Zhou


Maxim A Shevtsov,1,2 Larisa V Smagina,1 Tatiana A Kudriavtceva,3 Sergey V Petlenko,4 Irina V Voronkina1

1Institute of Cytology of the Russian Academy of Sciences (RAS), St Petersburg, Russia; 2IP Pavlov State Medical University of St Petersburg, St Petersburg, Russia; 3Institute of Experimental Medicine of the North-West Branch of the Russian Academy of Medical Sciences (IEM NWB RAMS), St Petersburg, Russia; 4Military Medical Academy, St Petersburg, Russia


Abstract: The management of chronic skin wounds represents a major therapeutic challenge. The synthesized dipeptide (Glu-Trp-ONa) and its acylated analogue (R-Glu-Trp-ONa) were assessed in the model of nonhealing dermal wounds in rabbits in relation to their healing properties in wound closure. Following wound modeling, the rabbits received a course of intraperitoneal injections of Glu-Trp-ONa or R-Glu-Trp-ONa. Phosphate-buffered saline and Solcoseryl® were applied as negative and positive control agents, respectively. An injection of Glu-Trp-ONa and R-Glu-Trp-ONa decreased the period of wound healing in animals in comparison to the control and Solcoseryl-treated groups. Acylation of Glu-Trp-ONa proved to be beneficial as related to the healing properties of the dipeptide. Subsequent zymography analyses showed that the applied peptides decreased the proteolytic activity of matrix metalloproteinases MMP-9, MMP-8, and MMP-2 in the early inflammatory phase and reversely increased the activity of MMP-9, MMP-8, and MMP-1 in the remodeling phase. Histological analyses of the wound sections (hematoxylin–eosin, Mallory’s staining) confirmed the enhanced formation of granulation tissue and re-epithelialization in the experimental groups. By administering the peptides, wound closures increased significantly through the modulation of the MMPs’ activity, indicating their role in wound healing.

Keywords: chronic wound, matrix metalloproteinases, small peptides

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