Regenerative effects of Gly-His-Lys and Gly-His-Lys-D-Ala peptides in infected skin wounds

Rakhmetova KK, Mishina ES, Vorvul AO, Bobyntsev II, Dolgintsev ME, Bezhin AI
About authors

Kursk State Medical University, Kursk, Russia

Correspondence should be addressed: Igor I. Bobyntsev
Karla Marxa, 3, Kursk, 305041, Russia; ur.liam@gibob

About paper

Author contribution: Rakhmetova KK — sample collection, concept and design of the study, data analysis and interpretation, writing of the manuscript; Mishina ES — histological and morphological examination, data analysis and interpretation; Vorvul AO — statistical processing of the data, writing of the manuscript; Bobyntsev II — concept and design of the study, scientific editing of the manuscript; Dolgintsev ME — data analysis and interpretation, writing of the manuscript; Bezhin AI — concept and design of the study.

Compliance with ethical standards: the study was approved by Ethics Committee of the Kursk State Medical University (Protocol № 1 of January 16, 2014). The study was carried out in compliance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes and the Guidelines for conducting preclinical drug trials (Moscow, 2012).

Received: 2022-02-10 Accepted: 2022-03-01 Published online: 2022-04-13

Skin wound healing mechanisms and new ways of improving their efficiency represent an important focus in medicine. In this regard, regulatory peptides, which exhibit physiological polyfunctionality and modulate cell growth and differentiation, are of special interest. This study evaluates the effects of Gly-His-Lys (GHK) and Gly-His-Lys-D-Ala (GHK-D-Ala) peptides in the infected skin wound healing. The wounds were modeled in rats (n=150) by full-thickness dorsal skin defects. The peptides were administered intracutaneously at daily doses of 0.5 or 1.5 µg/kg. The healing was assessed on days 3, 7, and 10 by histomorphometric examination of the wounds with adjacent intact skin. GHK-D-Ala administered at daily doses of 0.5 µg/kg had pronounced positive effect on regeneration processes in the wound, as indicated by significantly reduced numbers of granulocytes and lymphocytes with increased representation of fibroblastic lineages and macrophages, and the resulting higher cellular index (p < 0.05–0.001). At higher doses of GHK-D-Ala (1.5 µg/kg), the beneficial effects were less pronounced. According to the comparative morphological examination, the highest positive effect was achieved with 0.5 µg/kg of GHK-D-Ala. Thus, local administration of the GHK peptide with extra D-alanine at carboxy-terminus significantly mitigated the inflammatory reaction and facilitated the healing of infected skin wounds in rat model.

Keywords: inflammation, regeneration, Gly-His-Lys-D-Ala, GHK-D-Ala, infected wound