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Vol. 24, Art. 33 (pp. 440-447)    |    2023       

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Efficiency of a poly-adp-ribosylation inhibitor under high doses irradiation (experimental study)

Remizov D.V., Tikhomirov P.V., Kondakov A.Yu., Drachev I.S.

Federal State Budgetary Institution «State Scientific Research Test Institute of military medicine» Ministry of Defense of the Russian Federation

Brief summary

The present work is devoted to the study of the mechanisms of development of early post-radiation disorders of neurological symptoms in irradiated animals. The most pronounced changes in irradiation at ultrahigh doses occur in the GABAergic system closely associated with benzodiazepine receptors and are one of the causes of early post-irradiation disorders of neurological symptoms characteristic of cerebral radiation syndrome. Prophylactic use of ADP-ribosylation inhibitors may prevent the development of such manifestations. Purpose of the study. Study of the state of the GABA benzodiazepine system against the background of the use of an inhibitor of poly-ADP-ribosylation (nicotinamide) during superlethal irradiation. Materials and methods. The work was performed on non-linear white rats, which were irradiated in the cranio-caudal direction using the IGUR 1 device at doses of 100 and 150 Gy. The nature of spontaneous and induced motor activity, orienting and exploratory reactions were assessed, the time of appearance and severity of external signs of cerebral dysfunction (tremor, ataxia, disorientation, etc.) were noted. To assess the state of the GABAergic system, we used the method of determining the binding of 3H-GABA and 3H diazepam by synaptosomal brain membranes. Research results. During the study, it was found that during the first 5-10 minutes after irradiation at doses of 100 and 150 Gy, hyperreactivity develops in 60-70% of animals. At the same time, a decrease in purposeful motor activity was recorded in all irradiated rats. In addition, in experimental animals there was an inhibition of GABAergic receptors: 3H GABA - by 90% and 3H diazepam - by 82%. Prophylactic use of nicotinamide at a dose of 100 mg/kg contributed to the relief of early neurological disorders (ataxia, tremor, postural asymmetry, etc.) and prevented a decrease in the activity of enzymes: 3H GABA - 6 times, 3H diazepam - 1.7 times. Conclusion. Thus, exposure to ultrahigh doses causes a decrease in the sensitivity of GABA and benzodiazepine receptors, which leads to the development of early neurological disorders. The use of nicotinamide contributes to the restoration of receptor sensitivity to the initial values by the first hour of the study.


Key words

radiation exposure; central nervous system; nicotinamide; neurological disorders; GABA benzodiazepine receptors

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