Introduction: The His-Phe-Arg-Trp sequence corresponding to the 6-9th amino acid residue of the adrenocorticotropic hormone molecule (ACTH6-9) is the critical pharmacophore of all endogenous melanocortin receptor agonists. In order to effects prolongation it may be stabilized by the addition of the amino acid sequence Pro-Gly-Pro (PGP) to the C-terminus. The aim of this work was to study the effect of ACTH6-9-PGP (HFRWPGP) on the processes of memory consolidation in the model of passive avoidance conditioning in comparison with ACTH4-7-PGP effects. Materials and methods: The study was carried out on the model of passive avoidance conditioning. The effects of ACTH6-9-PGP were studied after its intraperitoneal injection to male Wistar rats at doses of 0.5, 5, 50, 150, and 450 μg/kg 15 minutes before the experiment, whereas the effects of ACTH4-7-PGP– under the similar conditions at doses of 50, 150, and 450 μg/kg. Results and discussion: It was found that ACTH6-9-PGP had a pronounced stimulating effect on the memory consolidation process in the dose range from 0.5 μg/kg to 150 μg/kg, significantly increasing the latent period of an animal entering the dark chamber. Administration of ACTH4-7-PGP led to an improvement in the consolidation processes of the acquired conditioned reflex at the doses of 50 μg/kg and 450 μg/kg. Conclusion: The range of effective doses of ACTH6-9-PGP is lower than that of ACTH4-7-PGP, which indicates the greater activity of HFRWPGP sequence in relation to memory consolidation processes and allows considering this peptide as a promising molecule for creating nootropic pharmacological drugs.
Objective: To study the effect of the ACTH6-9-Pro-Gly-Pro peptide (ACTH6-9-PGP) on the spectral parameters of heart rate variability (HRV) in Wistar rats during short-term exercise. Methods: The study involved 48 Wistar rats. ACTH6-9-PGP was once administered to the animals intraperitoneally at doses of 5, 50, and 500 µg/kg (3 groups of animals) in a volume of 1 ml/kg. Animals of the control group were injected with normal saline in an equivalent volume. Each group included 6 males and 6 females. HRV indicators were recorded using the Physiobelt 2.5.1 complex (Neurobotics, Russia). HRV analysis was performed by spectral parameters: total power of the spectrum of HRV (TP), the total power of the high-frequency component (HF) (ms2 , %), the total power of the lowfrequency component (LF) (ms2 , %), the total power of the very low-frequency component (VLF) (ms2 , %), LF/HF ratio (LF/HF), index of centralization (IC). The cardio signal was recorded 4 times: 1 – after adaptation to the device; 2 – 15 minutes after the injection of the peptide; 3 – after physical activity (2-minute treadmill run), and 4 – after a 15-minute rest. Results: An analysis of the initial values of the HRV indicators made it possible to establish a shift in the spectral characteristics toward the VLF component in the studied groups. Physical activity in the control group caused an increase in the power of HF, LF, and VLF, however, their ratio (VLF>LF>HF) did not change at all stages of the study. A single intraperitoneal injection of the ACTH6-9-PGP peptide at a dose of 5 μg/kg stabilized the HRV parameters at the initial level. The administration of the peptide at a dose of 50 μg/kg and moderate physical activity were accompanied by an increase in the power of HF and LF compared to the initial level. The percentage of frequency components after the exercise was LF>VLF>HF, and in the recovery period, it became VLF>LF>HF. After the administration of the peptide at a dose of 500 μg/kg, an increase in HF and LF, and a redistribution of the frequency components toward LF>HF>VLF were noted. During the recovery period, a decrease in HF, restoration of the percentage of frequency indicators VLF>LF>HF, and an increase in LF/HF and IC were found. Conclusion: A study of the effects of the ACTH6-9-PGP peptide on HRV in Wistar rats showed that a single intraperitoneal injection at a dose of 5 µg/kg promotes adaptation of laboratory animals to physical activity due to the activation of suprasegmental structures, and at doses of 50 and 500 µg/kg – predominant activation of the peripheral segments of the sympathetic and parasympathetic autonomic systems. Keywords: ACTH6-9-Pro-Gly-Pro, heart rate variability, physical activity, Wistar rats, spectral parameters.
Aim. To study the morphofunctional state of the colonic wall in rats when using the N–terminal analog of the adrenocorticotropic hormone (ACTH) ACTH6-9-Pro-Gly-Pro (ACTH6-9-PGP) peptide under chronic stress.Materials and methods. The study was performed on 55 male Wistar rats, which were divided into 5 groups (n = 11): group 1 – control group (administration of saline solution without stress); group 2 – chronic restraint stress (CRS) + administration of saline solution; group 3 – CRS + administration of ACTH6-9-PGP at a dose of 5 μg / kg; group 4 – administration of ACTH6-9-PGP at a dose of 50 μg / kg; group 5 – administration of ACTH6-9- PGP at a dose of 500 μg / kg. A histologic examination of the rat colon was performed. The histologic architecture of the colonic wall, the depth of crypts, and the number of goblet cells were assessed. Furthermore, the number of granulocytes, plasma cells, lymphocytes, macrophages, and mast cells was counted.Results. The study demonstrated that chronic (14 days) restraint stress resulted in the development of inflammations in the colonic wall of the animals. Intraperitoneal administration of ACTH6-9-PGP at doses of 50 and 500 μg / kg daily throughout the entire time of stress exposure prevented the development of stress-induced alterations observed in the control animals. At the same time, anti-inflammatory effects of the peptide in the colonic wall and a decrease in the level of corticosterone in the blood serum were noted.Conclusion. The results of this work and data from other studies on the effects of N-terminal analogs of ACTH indicate the need for studying the mechanisms of their effect on inflammation and searching for targets of ACTH6-9-PGP.
The aim of the study was to provide a comparative assessment of reparative osteogenesis activity and neutrophil func-tion when thymogen, dalargin, Gly-His-Lys (GHK) peptides and their paired combinations were injected into the experi-mental fracture area. Materials and methods. Peptides were administered to Wistar rats in the area of fracture for ten days from the day of injury. Equimolar single doses of the drugs were used: dalargin - 1.2 µg/kg, while thymogen and GHK were injected in a dose of 0.5 µg/kg weight. Reparative activity of osteogenesis was assessed histologically and radiologically. Phagocytic and oxygen-dependent activity of the blood neutrophils was determined. Results. All peptides and their paired combinations increased the activity of reparative osteogenesis. Even more pro-nounced bone repair activity was observed after the injection of GHK peptide in combination with dalargin or thymogen with maximum intensity in animals treated with combined administration of GHK and dalargin. The fracture of the femur bone in experimental rats was also accompanied by a decrease in phagocytic and oxygen-dependent activity of neutrophils. The peptides increased the indices of neutrophils activity more markedly when using paired combinations of peptides and with the manifestation of a corrective effect in animals receiving combined administrations of GHK and dalargin. Conclusion. Synergistic action of Gly-His-Lys peptides, thymogen and dalargin significantly enhances reparative and stimulating neutrophil function in tubular bone fractures and can be used to activate reparative osteogenesis and neutrophil bactericidal activity.
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