Bondariev Y. Experimental substantiation of optimization of cold injury prevention and treatment with the preparations targeting metabolism and inflammation

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0520U101482

Applicant for

Specialization

  • 14.03.05 - Фармакологія

08-10-2020

Specialized Academic Board

Д 64.605.03

National University of Pharmacy

Essay

The thesis represents the results of theoretical and experimental substantiation of the expediency of glucosamine preparations use in different types of cold injury (CI). The screening of potential frigoprotectors was performed on the model of acute general cooling (AGC) at –18 °C in mice. Among 13 potential frigoprotectors of natural or synthetic origin, 8 drugs or substances, namely glucosamine hydrochloride (G h/chl), "Glucosamine-C BHFZ," acetylsalicylic acid (ASA), "Corvitin", "Lipoflavon", "Lipin", ascorbic acid, Rhodiola liquid extract statistically significantly increased the survival time of animals on the model of AGC that is the evidence of frigoprotective activity. T The positive influence of G h/chl and "Glucosamine-C BHFZ" on the CNS state after AGC and acute local CI has been proven. It was shown that they cause the decrease in hypothermia severity, normalization of the excretory renal function and cardiovascular system state, positive influence on the adrenal cortex and skin structure and functioning. Glucosamine preparations improve blood rheological properties, exert significant anti-inflammatory and antiaggregant properties, reveal a pronounced anti-alcohol action. The study of the mechanisms of action allowed to clarify the influence of the leaders among the promising frigoprotectors on the proinflammatory and inflammatory interleukins (IL-1ß and IL-10 respectively) blood content after AGC in rats. In acute CI, IL-1ß blood level is significantly increased while IL-10 level is reduced, thus indicating the development of the inflammatory process. ASA, "Glucosamine-C BHFZ" and especially G h/chl exerted clear anti-inflammatory properties, as evidenced by a statistically significant decrease in IL-1ß level and an increment in the anti-inflammatory IL-10 content vs. the UC group indices. The level of cortisol in the blood after acute local CI was investigated in rats. G h/chl, "Glucosamine-C BHFZ" and, to a lesser extent, ASA, significantly lowered serum cortisol, confirming the aforementioned pronounced stress-protective properties of glucosamine preparations. G h/chl, "Glucosamine-C BHFZ" and, to a lesser extent, ASA under the conditions of both AGC and local CI (frostbite) contributed to the reliable normalization of lipid peroxidation and the antioxidant defense system markers in relation to the UC data. Notably that G h/chl exhibited more significant antioxidative properties that are involved into the mechanism of frigoprotective action. Blockade of different types of adrenoceptors (β1-, β2-, α1-) increased the sensitivity of the organism to AGC. Therefore, M-cholinoreactive and α1-adrenoreactive structures are involved into the mechanisms of G h/chl frigoprotective effect, which could act as a modulator of the functional state of the mentioned receptors. The influence of "Glucosamine-C BHFZ" on the resistance to cold in cadets was studied at the National Academy of the National Guard of Ukraine (NANGU) during winter field exercises. The dietary supplement "Glucosamine-C BHFZ" under the conditions of two-week exposure to low ambient temperatures during winter field exercises in cadets significantly reduced the risk of acute respiratory diseases, improved the adaptation of the body to long-term exposure to cold, and increased attention to given tasks and mental performance. Thus, the results of in-depth study of glucosamine preparations pharmacological properties substantiate consideration of G h/chl and "Glucosamine-C BHFZ" as promising frigoprotectors with a multi-vector mechanism of action and the ability to influence on the most of the main links of CI pathogenesis. By the criteria of the complex frigoprotective action and safety level glucosamine preparations statistically significantly exceed the standard modern frigoprotective drug ASA. The findings provide new opportunities for the use of glucosamine drugs in the treatment and prevention of CI of different etiologies and allow to extend the indications for G h/chl medical use, which to date has been mainly limited to chondroprotection. The results of the pharmacological research were implemented in the scientific-pedagogical process of 10 higher education institutions of Ukraine, 1 foreign higher educational institution and Rivne Regional Scientific Medical Library. On the basis of the dissertation materials, 54 scientific papers have been published

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