THE INFLUENCE OF ALKILSELENONAFTIRIDIN ON LEVELS IN BLOOD OF LIPOPROTEINS HIGH, LOW AND VERY LOW DENSITY ON A BACKGROUND OF EXPERIMENTAL DIABETES

Correction of disturbances in lipid metabolism by diabetes remains a problem today. The aim of this work was to study the impact alkilselenonaftiridin (ASNR) on the dynamics of changes in the blood serum of levels lipoproteins of high (HDL), low (LDL) and very low (VLDL) density on the background of experimental streptozotocin-induced diabetes (DM). ASNR (180 mg / 100 g) were administered daily from the first day and 21 ht day experiment in two different groups. It is shown that diabetes leads to changes in the lipid composition of blood – reducing the level of HDL and, conversely, increased LDL and VLDL levels. Introduc-tion ASNR positively influenced the change of levels these of lipoproteins. Especially in the case when ASNR administered on the first day of the experiment. In particular, the introduction ASNR the first day of the experiment prevents significant reduction of HDL levels, such as 8.3 and 9.9% on the 20 th and 40 th day of the experiment, respectively. ASNR prevents increasing of LDL levels on 13.3 and 10.4% on the 20 th and 40 th days experiment, respectively. Simultaneously, ASNR reduces the negative impact of DM on VLDL levels on 7.4, 11.1 and 21.4 % on the 20 th , 40 th and 60 th day experiment in accordance. However, the introduction of ASNR with 21 st day of the experiment has little effect on changes of levels lipoproteins, caused by the development of DM. Except reduction on 13.3 % the negative impact of diabetes on levels of VLDL on the 60 th day of the experiment. Thus, the introduction of ASNR positively influenced the change of levels lipoproteins of high, low and very low density on the background of experimental streptozotocin-induced diabetes.

This article is part of the research work of the department of anatomy, physiology of human and animal in «The University of Lugansk» «Mechanisms of adaptation to environmental factors» under the state registration number 0198U002641.
Introduction.Diabetes mellitus (DM) is one of the most pressing biomedical problems, which is a priority the direction of national health systems [1].In 2010 the total number of patients with all forms of diabetes in the world was about 239 million people.According to forecasts of the International Diabetes Federation (IDF), the number of patients with diabetes in the adult population (20-79 years) by 2030 will increase to 439 million [2].The highest percentage of patients with diabetes mellitus belongs to the second type (80-95%) [3,4].Among the European population prevalence of diabetes is 7.8%.Most of them suffer from diabetes in Germany (10.2% of the population) and in Belgium (10% population), at least in the United Kingdom (4.2% of the population), significantly at least -in the Western Pacific Region [5,6].In Ukraine, according to Ministry of Health, about 1.5 million peoples are suffering with diabetes.It is estimated that among the inhabitants of different countries over 65 years, every 20th person suffers from diabetes, and this figure shows only those who know about the disease, and is registered in endocrinologist [7].Diabetes accompanied by dangerous development of acute and chronic related disorders that lead to early disabilities and reducing life expectancy.Diabetes is a high risk for development blindness, renal failure, diabetic cardiomyopathy and encephalopathy [8].
Concerning experimental studies, the aim was to studying diagnosis and treatment of diabetes, that is ЕКСПЕРИМЕНТАЛЬНА МЕДИЦИНА Український журнал медицини, біології та спорту -№ 1 (3) important and timely.The purpose of this work was to study the impact alkilselenonaftiridin on the dynamics of changes in the blood serum of levels lipoproteins of high, low and very low density on the background of experimental streptozotocin-induced diabetes.
Methods.The study was carried out in the autumn-winter period on 92 male rats of Wister weighing 220-280 g, which were kept in a standard diet of the vivarium of the department of anatomy and physiology of animal of «Lugansk National University Taras Shevchenko» [9].Selection of rats for experiments was associated with the peculiarities of the methodological approach to the solution of the objectives and tasks.The number of experimental animals was determined according to the methods of statistical analysis [10].The content and care of rats was carried out on compliance with the principles of bioethics and the «European Convention for the Protection of Vertebrate Animals», which are used for experimental and other scientific purposes (Strasbourg, 1985), as well as the decisions of the «First National Congress on Bioethics» (Kiev, 2001) [11].
The control group consisted of 23 rats.In the 69 research groups of animals was modeled experimental streptozotocin-induced diabetes.All animals of the experimental group were divided into three subgroups (23 rats) each one.The animals of the first sub -group (1-EG) simulated of streptozotocin diabetes (DM) without introducing Alkilselenonaftiridin -ASNR (number 7498352, «Brillstein Handbook»).The animals of second sub-group (2-EG) ASNR started to enter 21st days from the beginning of the experiment and the animals of the third experimental subgroups (3-EG) ASNR started to enter the first day of the experiment.Daily dose ASNR (180 mg /100 g) was calculated in accordance with M.A. Ansari et al. (2004) and N. Stanishovski (2008) [12,13].
The animals were injected intraperitoneally research group streptozotocin («Sigma-Aldrich», USA) at a dose of 50 mg/kg body weight in 0.1mol citrate buffer (pH=4.5)once.To confirm the playback diabetes in rats under administration streptozotocin photometrically determined glucose in the blood serum using glucoseoxydase method («Agat-Med», Ukraine) and whole blood using a glucometer «Glucofort» (Ukraine) and glucose in urine -by using diagnostic strips «Pentafan» («Lachema», Czech Republic).
Results and Discussion.The level of high density lipoproteins (HDL) in the blood serum of animals control group before the experiment was 0.90± 0.11 mmol/l.By the 20 th day of the experiment HDL was 0.99±0.19mmol/l, after a 40-day experiment 0.95±0.18mmol/l and after 60-days 1.0±0.22mmol/l.
Baseline level of HDL in animals with experimental diabetes (1-EG) was 1,06±0,07 times higher than the control (0.95±0.17 mmol/l).After a 20 th day experiment HDL level decreased in 1.29±0.03times than exposure control and amounted to 0.77±0.14mmol/l.On 40 th and 60 th day experiment HDL levels increased with relative 20 th day rate to 0.82±0.15mmol/l (P<0.05) and 0.92±0.19mmol/l (Р<0.01) in accordance.In comparison with the exposure control revealed a decrease in HDL levels in 1.16±0.02and 1.08±0.02times accordingly.Thus in animals with experimental diabetes levels of HDL in the blood serum versus control animals were significantly reduced (Fig. 1).
In comparison with control animals 2-EG baseline in HDL was above 1.01±0.08times (0.91±0.17 mmol/l).Average level of HDL on a 20 th day experiment was reduced in 1.30±0.06times, to 0.76±0.16mmol/l (P <0.05).On a 40 th day exposure experiment HDL levels dropped relative to the exposure control in 1.13±0,02 times.In comparison to the 20 th day exposure experiment, the average of the level of HDL increased to 0.84±0.15mmol /l (P<0.05).After a 60 th day experiment the level of HDL increased to 0.97± 0.20 mmol/l (1.02±0.03times lower than the exposure control), P<0.05 (Fig. 1).
Animals with 3-EG before experiment had level of HDL 0.97±0.18mmol/l which is 1.08±0.09fold over control was.After a 20 th day experiment HDL level decreased to 0.84±0.18mmol/l (in 1.18±0.06times lower than the exposure control), P<0.05.On the 40th and 60 th day of the experiment revealed increasing of levels of HDL relative to 20th-day rate to 0.91±0.16mmol/l (P<0.05) and 0.96±0.20 mmol/l (P<0.05), and were reduced versus the control in 1.04±0.01and 1.01±0.25 times in accordance (Fig. 1).However, positive can be considered as mitigating negative impact of diabetes on the level of HDL.Namely, prevent a significant reduction in their levels on 8.3 and 9.9% on the 20th and 40th day experiment, respectively.
We can conclude that the level of HDL in animals of all experimental subgroups dropped to 20 th day of the experiment and then increased until the 60th day experiment, exposure, but remained below the exposure control.The changes were more in the animals of 1st and 2nd experimental groups.Thus, the introduction of animals of ASNR with first day of the experiment (group 3-EG) reduces the negative impact of DM on levels of HDL.Simultaneously, the introduction of ASNR with 21st day (group 2-EG) has little effect on changes in levels of HDL, caused by the development of DM.
The level of low-density lipoproteins (LDL) in the animals of the control group before the experiment was 0.24±0.05mmol/l.On the 20th day of the experiment the level of LDL was within 0.23±0.05mmol/l.On 40th day experiment was 0.26±0.06mmol/l and on 60th day was 0.22±0.07mmol/l.Baseline LDL animals with DM (group 1-EG) was (0.22±0.05 mmol/l) on 1.09±0.13times lower than the control.After a 20th day experiment the level of LDL increased in 1.42±0.20 times than the exposure control and amounted to 0.34±0.12mmol/l (P<0.05).On 40 th and 60 th day experiment the level of LDL dropped relative to 20 th day rate to 0.32±0.09mmol/l (P<0.05) and 0.28±0.12mmol/l (P<0.01).In comparison with the exposure control found an increase in the level of LDL in 1.23±0.13and 1,27±0.13times in accordance (Fig. 2).Thus in animals with experimental diabetes levels of LDL in the blood serum versus control animals were increased.
In comparison with the control animals in 2-EG baseline LDL was lower in 1.08±0.19times (0.26± 0.07 mmol/l).On a 20th day experiment the average of level of LDL was increased to 0.33±0.13mmol/l (in 1.43±0.227fold) when P<0.05.On 40 th and 60 th day experiment exposure LDL level was higher than the control in 1.15±0.16and 1.32±0.35times.But the average of level of LDL was less than in 20 th day -0.30±0.11 mmol/l (at P<0.05) and 0.29±0.10mmol/l (P<0.05) in accordance (Fig. 2).
In animals 3-EG LDL level before the experiment was 0.23±0.08mmol/l, which in 1.04±0.231times was lower than the control.On a 20 th day experiment LDL level increased to 0.30±0.12mmol/l (in 1.30±0.23 times the exposure control) when P<0.05.On the 40 th and 60 th day of the experiment revealed a decrease in LDL level relative to 20 th day rate to 0.29±0.11mmol/l (P<0.05) and 0.28±0.11mmol/l (P< 0.05) in accordance, and remained above the exposure control in 1.12±0.17and 1.27±0.37times in accordance (Fig. 2).
Thus, the introduction of ASNR with first day of the experiment (3-EG) reduces the negative impact of DM on levels of LDL.Namely, prevent increase their level on 13.3 and 10.4% on the 20th and 40th day experiment, respectively.Simultaneously, the intro-duction of ASNR with 21st day (3-EG) has little effect on changes in levels of LDL, caused by the development of DM (Fig. 2).
The level of very low density lipoproteins (VLDL) the animals of the control group before the experiment the VLDL level in serum was 0.34±0.10mmol/l.By the 20 th day of the experiment the level of VLDL was within 0.36±0.09mmol/l, on a 40 th day experiment was 0.34±0.06mmol/l and on 60 th day was 0.32±0.12mmol/l.
Baseline level of VLDL animals with experimental diabetes (1-EG) was in 1.03±0.10time increase over control (0.35±0.10 mmol/l).On a 20 th day experiment the VLDL level increased in 1.61±0.12times than the exposure control and amounted to 0.58±0.15mmol/l (P<0.05).On 40 th and 60 th day experiment the VLDL level dropped relative to 20 th day rate to 0.50± 0.12 mmol/l (P<0.05) and 0.51±0.21mmol/l (P<0.05) in accordance.In comparison with the exposure control found an increase in the level of VLDL in 1.47± 0.16 and 1.59±0.44times accordingly (Fig. 3).Thus in animals with experimental diabetes levels of VLDL in the blood serum versus control animals were significantly increased.
In comparison with the control animals in 2-EG animals, the VLDL baseline level was below in 1.06± 0.09 times (0.32±0.11 mmol/l).After a 20 th day experiment the average of the level of VLDL in 2-EG animals increased in 1.84±0.01times to 0.59±0.14mmol/l (P<0.05), and in 1.64±0.02(P<0.05) and 1.02±0.01times compared to the control and diabetic animals respectively.On 40 th and 60 th days of exposure experiment the VLDL level dropped relative to 20 th day and was 0.48±0.09mmol/l (P<0.05) and 0.45± 0.19 mmol/l (P<0.05) in accordance (Fig. 3).
Baseline level of VLDL before the experiment in 3-EG animals (0.35±0.11 mmol/l) was in 1.031± 0.099 times increase in comparison with control.On a 20 th day experiment VLDL levels increased to 0.54± 0.12 mmol/l (in 1.478±0.087times relatively control, P<0.05), however, less than in animals with diabetes (in 1.07±0.01times).On the 40 th and 60 th days of the experiment revealed lowering VLDL with respect to 20 th day rate to 0,45±0.10 mmol/l (P<0.05) and 0.42± 0.19 mmol/l (P<0.05).VLDL level remained above in comparison with control in 1.32±0.08 and 1.31±0.25 times, respectively.Simultaneously, VLDL levels on the 40th and 60th days of the experiment in this group were significantly lower VLDL levels in animals with diabetes, namely in 1.32±0.08 and 1.31±0.25 times in accordance (Fig. 3).
Thus, the introduction ASNR with 21 st day of the experiment (2-EG) reduces (on 13.3 %) the negative impact of DM on levels of VLDL only on the 60 th day of the experiment.Simultaneously, the administration of ASNR with first day of the experiment (group 3-EG) reduces the negative impact of DM on VLDL levels on 7.4, 11.1 and 21.4 % on the 20 th , 40 th and 60 th day experiment, respectively.

1 Figure 3 .
Figure 3.The level of very low density lipoproteins in the blood serum of animals in the control (1) and the experimental group 1-EG (2), 2-EG (3) and 3-EG (4).