Effects of Neonatal Administration of Non-Opiate Analogues of Leu-Enkephalin to Heart Tissue Homeostasis of Prepubertal Albino Rats Exposed to Hypoxia.

Hypobaric hypoxia (pO2 65 mm Hg, duration 4 h) induced a significant increase in the number of cardiomyocytes expressing р53, beclin-1, endothelial NO synthase and accumulation and degranulation of mast cells in the epicardium in hearts of prepubertal female rats (age 45-47 days); the number of cardiomyocytes with nucleoli decreased, while the number of single-nucleolar cardiomyocytes increased after this exposure. Five-fold administration of non-opiate analogue of leu-enkephalin (NALE peptide: Phe-D-Ala-Gly-Phe-Leu-Arg; 100 µg/kg) during the neonatal period reduced the severity of the post-hypoxic changes in the heart. Neonatal administration of NALE (100 µg/kg) against the background of NO synthase blockade with L-NAME (50 mg/kg) did not abolish the cardioprotective effects of the peptide. A similar correction of posthypoxic changes in the heart was observed after neonatal administration of original peptide G (Phe-D-Ala-Gly-Phe-Leu-Gly; 100 µg/kg). Thus, NO synthase-NO system and C-terminal amino acid Arg in the molecule of non-opiate analogue of leu-enkephalin are not required for the cardioprotective effects of peptides. Non-opiate leu-enkephalin analogs, peptides NALE and G, can be considered as promising substances for increasing heart resistance to hypoxia during later age periods.

Role of Amino Acid Arginine and Nitric Oxide in Mechanisms of Cytoprotective Effect of Non-Opiate Leu-Enkephalin Analogue In Vitro.

Incubation of primary culture of pulmonary fibroblasts with non-opiate analogue of leuenkephalin (NALE; Phe-D-Ala-Gly-Phe-Leu-Arg, 0.1 µM) reduced generation of superoxide anion-radical (by 20.7%) and decreased the number of p53+ cells (by 40.2%) induced by exposure to H2O2 (60 µM). The cytoprotective effect of NALE was potentiated by NO synthase inhibitor L-NAME (1 mM): the number of p53+ cells decreased by 65.3% and morphometric parameters of the cell nuclei and nucleoli were improved. Incubation of pulmonary fibroblasts culture with peptide G (Phe-D-Ala-Gly-Phe-Leu-Gly, 0.1 µM) also significantly reduced the damaging effect of H2O2: the number of p53+ cells decreased by 73.5%, the area of cell nuclei returned to normal, and generation of superoxide anion-radical decreased by 18.4%. These results indicate that C-terminal amino acid Arg and activation of NO synthase are not involved in the direct cytoprotective effect of NALE.

Effect of MGHPPGP Peptide Administered during the Post-Traumatic Period on Morphometric Parameters of the Neocortex and Hippocampus, Hepatocytes, and Epithelium of the Tongue and Small Intestine in Rats.

The effect of glyproline-containing peptide MGHPPGP (Met-Glu-His-Phe-Pro-Gly-Pro) was studied in experiments on male Wistar rats with modeled traumatic brain injury. The peptide was administered intraperitoneally in a dose of 1 mg/kg in 3 h and on days 2, 3, 4, 5 after injury. We evaluated morphometric parameters of the epithelial cells of the tongue, small intestine, and liver cells (AgNOR staining), neuronal layers II and V of the neocortex of the parietal lobe and hippocampal CA1 field (staining with gallocyanin) were evaluated in the post-traumatic period. Traumatic brain injury (TBI) was induced in rats by using the impact model (WDM; weight drop method). MGHPPGP peptide corrected the activity indicators of the nuclear organizer regions in epitheliocytes of the tongue.