The effect of arginine-containing glyproline PRPGP on DNA synthesis and free radical oxidation in the mucosa of the stomach of white mice on the model of indomethacin-induced ulcer formation

Written by Tolstenok I.V., Lebedko O.A., Andreeva L.A., Innokentev A.A., Fleushman M.Yu.

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Objective. The effect of the oligopeptide Pro-Arg-Pro-Gly-Pro (PRPGP) on DNA synthesis and free radical oxidation in the epithelium of the gastric mucosa on the model of gastroindomation induced by indomethacin was studied.
Methods. The work was performed on 59 white mice injected with PRPGP (5 days to 1 mg/kg) and intra-gastric indomethacin (on day 5, 250 mg/kg) intramargibly administered. In the stomachs of mice after excretion of animals from the experiment, the area of erosive ulcerative lesions of the mucosa, the synthesis of DNA (autoradiography with 3H-thymidine), and the intensity of free radical oxidation (chemiluminescence) were measured.
Results. Under physiological conditions, the administration of the peptide did not cause changes in the gastric mucosa. After the introduction of indomethacin, erosive and ulcerative lesions of the mucous membrane developed, the index of labeled nuclei decreased in the stomach tissue and the intensity of free radical oxidation increased.
Conclusions. Under the influence of indomethacin in the mucous membrane of the stomach of white mice, oxidative stress developed. Glyproline PRPGP weighted the processes of free radical oxidation. The inversion of the action of the peptide in this study can be explained by the dose-dependent effect of nitric oxide. The theoretical concentration of nitric oxide formed from the peptide after proteolysis was calculated. It was found to be 22.3 μM. Exceeding the threshold concentration of nitric oxide (1 μM) caused the activation of poly (ADP-ribose) polymerases, disruption of mitochondria and accumulation of calcium ions, which led to apoptosis through a cascade of consecutive reactions.

Links to authors:

I.V. Tolstenok1, O.A. Lebedko1, 2, L.A. Andreeva3, A.A. Innokentev1, M.Yu. Fleushman1
1 Far Eastern Medical University (30 Muravyeva-Amurskogo St. Khabarovsk 680000 Russian Federation),
2 Khabarovsk branch of the Far Eastern Scientific Center of Physiology and Pathology of Respiration – RI of the maternity and child welfare service (49/1 Voronezhskaya St. Khabarovsk 680022 Russian Federation),
3 Institute of Molecular Genetics of the Russian Academy of Sciences (2 Akademika I.V. Kurchatova Sq. Moscow 123182 Russian Federation)

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