Studying the effects of regulatory peptides on the stress-induced shifts in the bodily processes is of great fundamental and applied significance. Currently, a wide range of peptide neurotropic drugs, affecting the stress response development, are used in medicine, and new promising molecules are being studied. The study was aimed to assess the effects of the adrenocorticotropic hormone (ACTH) synthetic analog, ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5, 50 and 500 μg/kg, on the free-radical oxidation processes in Wistar rats, subjected to chronic restraint stress (CRS) during two weeks. Serum levels of 8-oxo-2'-deoxyguanosine (8-OHdG) and superoxide dismutase 3 (SOD3) were assessed by enzyme immunoassay, and the levels of thiobarbituric acid reactive substances (TBARS) were assessed by fluorimetric method. CRS lead to the significant increase in the 8-OHdG levels by 18.4% (p = 0.01) and the decrease in the SOD3 levels by 14.3% (p = 0.01), however, it had no effect on the levels of TBARS. ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5 and 50 μg/kg, significantly decreased the levels of 8-OHdG by 19.8% (p = 0.03) and 30% (p = 0.001), respectively. Thus, it was found that CRS resulted in oxidative stress in animals. ACTH(6-9)-Pro-Gly-Pro administration at a dose of 5 and 50 μg/kg inhibits the stress-induced free-radical oxidation processes.

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.