title: 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.
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.
authors.affiliation: Institute of Cytology of the Russian Academy of Sciences (RAS), St Petersburg, Russia ; IP Pavlov State Medical University of St Petersburg, St Petersburg, Russia.
authors.forename: Maxim A
authors.initials: MA
authors.lastname: Shevtsov
authors.affiliation: Institute of Cytology of the Russian Academy of Sciences (RAS), St Petersburg, Russia.
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Smagina
authors.affiliation: Institute of Experimental Medicine of the North-West Branch of the Russian Academy of Medical Sciences (IEM NWB RAMS), St Petersburg, Russia.
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Kudriavtceva
authors.affiliation: Military Medical Academy, St Petersburg, Russia.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Petlenko
authors.affiliation: Institute of Cytology of the Russian Academy of Sciences (RAS), St Petersburg, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Voronkina
mesh_terms: D000215:Acylation; D000818:Animals; D002908:Chronic Disease; D004151:Dipeptides / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D011817:Rabbits; D012867:Skin / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D004151:Dipeptides
keywords: chronic wound; matrix metalloproteinases; small peptides
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