Protective Effect of Dermorphin Analogue Sedatin on Indomethacin-Induced Injury to the Gastric Mucosa

Abstract

Administration of indomethacin (250 mg/kg) to mice was followed by the formation of severe ulcerative and erosive injury to the gastric mucosa, inhibition of DNA synthesis, and development of oxidative stress. Fivefold pretreatment with sedatin (100 microg/kg) decreased the area of indomethacin-induced ulcers and erosions, stimulated DNA synthesis, and reduced the severity of oxidative stress. Non-arginine dermorphin analogue did not stimulate DNA synthesis and had no effect on the degree of oxidative stress. After pretreatment with L-NAME, sedatin did not modulate the synthesis of DNA under conditions of indomethacin-induced injury to the gastric mucosa.

Gastroprotective Oligopeptides

“…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…”

“…Copyright: ©2015 Nasadyuk et al Н-thymidine showed that the administration of sedatin in different doses stimulated DNA synthesis in epithelium of the gastric mucosa [5,30]. Endogenous opioids have been implicated in the process of gastric sensitivity and gastric motor responses, and impairment of antinociceptive opioid pathways, that is hypothesized to contribute to the pathogenesis of functional dyspepsia [46].…”

“…It is commonly acknowledged that nonsteroidal anti-inflammatory drugs (NSAIDs), being the most commonly prescribed group of drugs worldwide for the management of pain and inflammation, play an important role in provoking gastrointestinal tract ulceration, bleeding and perforation [1,4,5]. This mediates the necessity of the effective gastroprotective measures in patients, who are at risk of gastric ulceration, in particular chronic NSAIDs users.…”

“…Nowadays for this purpose proton pump inhibitors and H 2 -antagonists are commonly used, but due to side effects of these drugs the search for new compounds with gastroprotective properties, suitable for longterm use, remains actual [1,2]. Contemporary literature gives accumulating evidence that a number of oligopeptides play an important role in the regulation of the function of gastrointestinal tract and their synthetic analogues were reported to be effective in the prevention and treatment of gastric ulceration [1,[5][6][7][8][9][10][11][12].That is why the purpose of this review was to summarize the current data on the oligopeptides with documented gastroprotective properties and their possible mechanisms of action. …”

“…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 …”