Comparison of the effects of three glyprolines after five days of intraperitoneal administration

Abstract

To date, about 70 drugs based on regulatory peptides have been registered, including proline-containing ones, such as the nootropics Semax and Selank. Further study of the properties of glyproline peptide sequences is relevant in order to describe their neuroprotective properties and the possible development of new drugs based on them. The purpose of the study was to compare the effects of three glyproline peptides on the morphometric characteristics and proliferative activity of brain cells in albino rats. Material and methods. Sexually mature Wistar male rats were intraperitoneally injected with the peptides Thy-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP), Arg-Pro-Gly-Pro (RPGP) and Pro-Gly-Pro-Leu (PGPL) at a dose of 0.1 mg/kg for 5 days. The intact animals that received 0.9 % sodium chloride solution in equivolume served as controls. Morphocytometry was performed on preparations of the right hemisphere of the brain after staining with hematoxylin and eosin. The dimensional (area of bodies, nuclei, and nucleoli) and numerical (number of nucleoli) characteristics of cells were assessed. We examined the parameters of neurons and gliocytes in five localizations (the second and fifth layers of the anterior parietal lobe, the second and fifth layers of the proprietal lobe, field CA1 of the hippocampus). Using immunohistochemical staining, the proliferation intensity was determined (marker Ki-67, clone MIB1). Results. The TKPRPGP peptide changed the morphometric parameters of nervous tissue cells and the gliocyte proliferation index to a greater extent than RPGP and PGPL. In our experiment, the proliferative activity of neurons is maximally influenced by glyproline PGPL. The arginine-containing compound RPGP activates the proliferative activity of gliocytes. Leucine-containing PGPL, to a greater extent, changes the morphometric parameters of neurons. Conclusions. Both studied tetrapeptides affect the morphometric characteristics and proliferative activity of nervous tissue cells when administered five times intraperitoneally at a dose of 0.1 mg/kg. When comparing glyprolines, a more pronounced effect was observed after the administration of PGPL.

Keywords

• glyprolines
• peptides
• thr-lys-pro-arg-pro-gly-pro
• arg-pro-gly-pro
• arg-pro-gly-pro
• pro-gly-pro-leu