Effects of GHK peptide and its structure analogues, D-Ala-GHK AND GHK-D-Ala, on innate immunity and lipid peroxidation processes in skin wound

Abstract

Objective: to study the effects of the GHK peptide and its structure analogues on the mechanisms of innate immunity and lipid peroxidation in wound. Materials and methods. The experiments were performed on 70 male Wistar rats. The skin wound was modeled by applying a full-layer wound with an area of 250 mm2 on the animal's back. The peptides Gly-His-Lys (GHK), D-Ala-Gly-His-Lys (D-Ala-GHK), and Gly-His-Lys-D-Ala (GHK-D-Ala) were used in doses of 0.5 μg/kg and 1.5 μg/kg, which it was administered intradermally in doses of 0.5 μg/kg and 1.5 μg/kg in a volume of 0.1 ml for 3, 7 or 10 days. The activity of lipid peroxidation (LPO) processes in blood serum was assessed by the content of malonic dialdehyde (MDA) and acylhydroperoxides (AHP). The antioxidant mechanisms were evaluated by determining the activity of catalase and the total antioxidant activity (OAA) of blood serum. Phagocytic activity of blood neutrophils was assessed by phagocytic index (PI) and phagocytic number (PN). The activity of oxygen-dependent mechanisms in phagocytes was evaluated in a spontaneous nitroblue tetrazolium test (NBT). Results. After the administration of GHK, the tendency to PI, PN and completeness of phagocytosis prevailed, which mainly persisted with the use of peptides D-Ala-GHK and GHK-D-Ala. At the same time, the GHK-D-Ala peptide at a dose of 1.5 μg/kg had the most stable effect on phagocytic activity. The data obtained in the NBT are largely consistent with the PN indicators. At the same time, the effects of structural analogues, unlike GHK, were manifested throughout the experiment. Significantly significant changes in the activity of LPO and antioxidant mechanisms were observed with the use of all peptides. However, their dynamics, orientation and severity throughout the experiment were quite complex. Conclusion. GHK and its structural analogues, D-Ala-GHK and GHK-D-Ala, had an effect on the indicators of innate immunity and LPO in a skin wound, the severity and direction of which depends on the healing period. At the same time, the most pronounced and stable effects were observed when using GHK-D-Ala. That demonstrates the importance of protecting the tripeptide molecule from the action of carboxypeptidases.