Effect of Glyprolines on Homeostasis of Gastric Mucosa in Rats with Stress Ulcers

Abstract

Pro-Gly-Pro and its metabolite Gly-Pro effectively prevented the development of erosive and ulcerative lesions of the gastric mucosa in rats under conditions of water-immersion restraint stress by restoring the oxidatant-antioxidant balance in the total fraction of gastric mucosa cells. Pro-Gly was least effective in this respect. We conclude that glyprolines hold much promise as pharmaceutical products, which can be used in gastroenterological practice for the prevention and therapy of ulcer disease of the stomach and duodenum.

Gastroprotective Oligopeptides

“…Oligopeptides were shown to be involved in the regulation of intracellular communication processes, nociception, vessel permeability, neoangiogenesis, nervous impulse transduction as well as affect the activity of hormones and enzymes and exhibit neuro-and immunomodulatory effects [13][14][15][16][17][18][19][20][21]. It is also hypothesized that biological activity of short peptides is mainly associated with their prominent antioxidant properties, although this data is a little bit contradictory as some compounds were reported to have an opposite effect, increasing the processes of oxidation [2,8,16,[24][25][26].Due to the recent literary data, the most explored representatives of oligopeptides with gastroprotective properties are met-enkephaline (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) [27,28] and leu-enkephaline (Tyr-Gly-Gly-Phe-Leu) [27][28][29], demorphine (Н-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH 2 ) and sedatine (H-ArgTyr-D-Ala-Phe-Gly-OH) [5,30], pentadecapeptide BPC 157 (GlyGlu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) [10,[31][32][33]; proline-and hydroxyproline-containing products …”

“…Thus, introduction of glyprolines caused the decrease of the area of gastric lesions induced by stress, ethanol, indomethacin and pylorus ligation [9,24,25,35,36]. It was documented that glyprolins posess not only protective untiulcer properties, but also accelerate ulcer healing [7,9,24,25,35,36,40].The most prominent untiulcer effects on all models of ulceration were evaluated in Pro-Gly-Pro and Pro-Gly-Pro-ProGly-Pro [7,24,25]. Due to the literary data the untiulcer effects of Pro-Gly, Pro-Gly-Pro, Gly-Pro-Gly-Pro and Gly-Pro-Gly-Pro-GlyPro, administered intraperitoneally, made 71%, 72%, 64% and 60% respectively; and 83%, 64%, 72% and 65% in the case of intragastral administration [7,9,24,25,35,36,40].…”

“…It was documented that glyprolins posess not only protective untiulcer properties, but also accelerate ulcer healing [7,9,24,25,35,36,40].…”

“…On the model of acetate-induced lesions of the gastric mucos, glyprolines were reported to decrease the severity of inflammation in the zone of ulcer defect both in the period of formation of the ulcerative defect and during healing [7,9,24,25,35,36,40]. The anti-inflammatory effect of glyprolines is proved by significant decrease of the number of polymorphonuclear leukocytes in the ulcer zone [7,9,24,25,35,36,40].Accelerating healing of the acetic acid lesions of the stomach on experimental models, glyprolines caused earlier total differentiation of the superficial epithelium and glands of the gastric mucosa, promoted the production of the large amount of fibroblasts in the place of regenerating ulcer and decreased the number of macrophages [7,9,24,25,35,36,40]. The studies conducted in rats with gastric lesions, caused by ethanol application and water-immersion restraint stress provide data that prominent preventive effect of Pro-Gly-Pro and Gly-Pro are determined by antioxidant properties of these substances [24,25].…”

“…The anti-inflammatory effect of glyprolines is proved by significant decrease of the number of polymorphonuclear leukocytes in the ulcer zone [7,9,24,25,35,36,40].…”