THE INFLUENCE OF ANGIOLIN ON THE MORPHOLOGICAL AND FUNCTIONAL PARAMETERS OF CA1 REGION OF THE HIPPOCAMPUS AND ON THE NEUROAPOPTOSIS PROCESSES IN EXPERIMENTAL CHRONIC ALCOHOL INTOXICATION UNDER THERAPEUTIC MODE OF ADMINISTRATION

Belenichev I. F., Pavlyuk I. V., Abramov A. V., Kucherenko L. I.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Nowadays the urgent problem of pharmacology is the development of new methods of neuroprotection in chronic alcoholism. The paper deals with neuroprotective activity of new original neuroprotector and cardioprotector with endotelioprotective effect — Angiolin ((S)-2,6-diaminohexanoic acid 3-methyl-1,2,4-triazolyl-5-thioacetate). Experiments have been performed on 70 white outbred male rats weighing 160-180 g, which received intragastric ethanol daily under the scheme: the first 10 days — 15% solution at a dose of 4 g/kg, following 10 days — 15% solution at a dose of 6 g/kg, and next 10 days the rats received 25% solution in a dose of 4 g/kg. In our investigations Angiolin tablets, 200 mg, producted by JSC «Kievmedpreparat», and Mildronat capsules, 250 mg, producted by JSC «Grindeks» (Latvia) were used. At the end of the experiment the animals were anesthetized with sodium thiopental (40 mg/kg) and the brain was removed, which was placed into Bouin’s fluid for one day and after standard histological procedure tissue was embedded in paraffin. To examine the morphology of neurons 5 microns microscopic sections of CA1 region of the hippocampus were prepared on rotary microtome. Hippocampus microscopic sections were de-embedded and dyed for determining the nucleic acids by Einarson gallocyanin-chrome alum. The morphometric study was carried out on Axioskop microscope (Ziess, Germany), 40×magnification. Microscope images of neurons in CA1 region of the hippocampus obtained with the help of highly sensitive video camera COHU-4922 (COCHU Inc., USA) were input into computer hardware and software system of digital image analysis VIDAS. Image analysis was carried out in semi-automatic mode. Comparison of groups was performed with the Mann-Whitney U test. Under the formation of chronic alcohol intoxication during 30 days in rats in the untreated (control) group decrease of density, area and contents of RNA in neurons and glial cells of the CA-1 region of the hippocampus was noted, as well as increase of the density and the proportion of apoptotically changed cells. Angiolin 14-days therapy (100 mg/kg, intragastric) performed after 30 days alcoholization had a significant positive effect on the area and density of both the neurons and glial cells, as well as on the RNA content in them, and significantly reduced the apoptotic processes. Angiolin neuroprotective properties are conditioned by the conversion of L-lysine, which is the part of the molecule structure, into pipecolic acid which potentizes the affinity of GABA- benzodiazepine receptor complex that results in the decrease of glutamate excitotoxicity and reduction of neuronal death. Neuroprotective and antiapoptotic effect of Angiolin is higher in all studied parameters as compared with reference preparation Mildronate (250 mg/kg, intragastric adminictration). The results received are experimental ground for the inclusion of Angiolin in the traditional scheme of alcoholism treatment.

chronic alcohol intoxication, neuroprotection, neuroapoptosis, Angiolin, Mildronate

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