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.
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.
Цель исследования: изучение влияния АКТГ 6-9-PGP на уровень депрессивности у крыс в тесте принудительного плавания в сравнении с АКТГ 4-7-PGP. Материалы и методы. Эксперименты выполнены на 90 половозрелых крысах-самцах Вистар массой 250-300 г. Животные были разделены на 9 групп (8 опытных и 1 контрольная) по 10 особей в каждой. В работе применяли физиологический раствор 0,9% натрия хлорида, пептиды АКТГ 6-9-PGP и АКТГ 4-7-PGP, синтезированные в Институте молекулярной генетики РАН. Пептиды вводили однократно внутрибрюшинно за 15 мин до начала тестирования: АКТГ 6-9-PGP в дозах 0,5; 5; 50; 150 и 450 мкг/кг, АКТГ 4-7-PGP в дозах 50; 150 и 450 мкг/кг. Депрессивное поведение крыс оценивали с использованием теста принудительного плавания без отягощения. Результаты. Внутрибрюшинное введение АКТГ 6-9-PGP в дозе 450 мкг/кг способствует уменьшению времени иммобилизации животных и пассивного плавания, а также увеличению длительности их активного плавания, что свидетельствует о наличии антидепрессивного действия пептида. При этом АКТГ 4-7-PGP во всех использованных дозах не оказывал существенного влияния на исследуемые показатели поведенческой активности, а его эффекты ограничивались лишь увеличением времени пассивного плавания. Заключение. Таким образом, установлено, что АКТГ 6-9-PGP, в отличие от АКТГ 4-7-PGP, способен обладать антидепрессивным эффектом. Ключевые слова: регуляторные пептиды; АКТГ; депрессия; принудительное плавание; крысы.
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.
Currently, there is no scientifically substantiated information on the occurrence of dental hyperesthesia and its causes in patients who have undergone a new coronavirus infection COVID-19. Objective: to study the occurrence of dental hyperesthesia, to analyze the causes and to find ways to eliminate it in elderly patients after a new coronavirus infection COVID-19. Material and methods. The incidence of dental hyperesthesia was studied in 175 elderly people (from 61 to 75 years old) who had a new coronavirus infection COVID-19 2-4 months ago. As a control group, 125 elderly people were examined, who had not suffered from a new COVID-19 coronavirus infection before their examination. Functional resistance of hard tissues of teeth was assessed using the index of enamel resistance test (TER-test) according to V.R. Okushko and oral hygiene using the simplified index of oral hygiene of Green-Vermillion OHI-S. Results. It has been established that in the postcovid period, dental hyperesthesia is more common in elderly patients, the cause of which is the demineralization of tooth enamel due to the deterioration of individual oral hygiene. Generally accepted oral hygiene in elderly people suffering from dental hyperesthesia contributes to the normalization of the TER-test indicators with a period of 3 to 6 months of regular dental and oral care. The additional use of remineralizing ASEPTА gel for teeth by patients during dental care made it possible to achieve high structural and functional resistance of tooth enamel during the quarter. Conclusion. In people who have undergone a new coronavirus infection COVID-19, due to the deterioration of the hygienic condition of the oral cavity, there is a decrease in the mineralization of hard tooth tissues, which is a factor in the occurrence of dental hyperesthesia and confirms the crystal chemical theory of this pathology. The additional use of remineralizing ASEPTА dental gel for individual dental and oral care makes it possible to achieve high caries resistance of tooth enamel in a shorter time.
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