Holyshkin D. The influence of melanin and nanocrystalline cerium dioxide on the state of gastric mucosa and the adrenal cortex reaction in the conditions of acute stress.

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0418U001285

Applicant for

Specialization

  • 03.00.13 - Фізіологія людини і тварин

28-02-2018

Specialized Academic Board

Д 26.001.38

Taras Shevchenko National University of Kyiv

Essay

It was shown that severity of GM damage was significantly lower when melanin was administered 30 minutes before the stress at a dose of 5 mg/kg (в.ш.) and NCD at a dose of 1 mg/kg (в.ш.) compared to the stress-control group. The decrease of erosions under the influence of both substances was found at trends. After three hours of neuromuscular stress by Selye, the mass of the adrenal glands increased, while the thymus decreased. Under conditions of prophylactic administration of melanin and NCD, the adrenal and thymus mass ratios were at level of the control. It has been demonstrated that prophylactic administration of melanin and NCD prevents stress-following degradation of protective collagen and non-collagen proteins of the mucosal-epithelial gastric barrier, indicating by a decrease in the concentration of free oxyproline, fucose and hexuronic acids. In this case, the integrity of the mucous barrier was close to the values of control rats that confirmed by the results of macroscopic analysis of the GM. Prophylactic administration of melanin and NCD resulted in the restoration of an excited pro-and antioxidant balance in the rats GM under acute stress conditions, which is confirmed by the activation of the enzymes of the antioxidant defense and the decrease in the content of lipid peroxidation products. Melanin and NCD exhibited immunomodulatory properties by action on stress-induced shift in blood leukocyte formula and stabilization of pro- and anti-inflammatory cytokines level. As a result, melanin single injection, produced more pronounced protective effect on the GM compared with NCD under acute stress conditions. Therefore, further research was focused on the study of the melanin polyphenolic compound. It was shown that the administration of melanin affected the stabilization of the levels of ACTH and cortisol in the rat serum. The mechanism of melinin penetration through the central hydrophobic zone of cell membranes was proposed for the first time. It was shown on the basis of established membranotropic activity. It is realized by increasing the conductivity and decreasing the electric capacity of the lipid bilayer model. This explains the implementation of the antioxidant properties of melanin at the cellular level. The obtained results resolve deepens understanding of the stress-protective effect of melanin and NCD on the stomach mucous membrane. These compounds are promising instruments of pharmacological stresses correction and could be recommended for further preclinical investigation. Such drugs are necessary for the prevention and treatment of the consequences of hostilities, catastrophes and surgical interventions. They can be used in any situations that cause psycho-emotional stress and the tension of adaptation mechanisms.

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