CC BY
24
ние обмена моноаминов и процессов окислительного
дезаминирования.
Литература
1. Жуков В.И., Попова Л.Д., Зайцева О.В., Кратенко Р.И. и др. Простые и макроциклические эфиры: Научные основы охраны водных объектов. - Харьков, Торнадо, 2000,-438 с.
2. Акопян А.А.. Арутнян М.В., Агавелян А.М.. Роль моноами-нооксидазы в патологии толстой кишки // Вопросы мед химии. - 1994. - Т. 40,№6. - С. 54-57.
3. Акопян А.А., Промыслов М.Ш. Моноаминооксидаза мозга при черепномозговой травме. // Вопросы мед химии. -1984. - Т.30,№ 1. - С. 75-77.
4. Бурчинский С.Г., Кузнецов С.М. Моноаминооксидаза мозга и ее ингибиторы в геронтологии // Вопросы мед химии. - 1988. - №4. - С. 2-9.
5. Ашмарина И.П., Ступалова П.В.. Нейрохимия. Москва, 1996. - 427 с.
6. Горошинская И.А. Роль моноаминооксидазы в реакции организма на экстремальное воздействие. Диссертация на соискание ученой степени д.б.наук, Ростов - на - Дону, 1998. - 411 с.
7. Камышанская Н.С., Гокин В.З.,Войтенко Н.Н. Множественные формы МАО головного мозга крысы при экстремальной кататонии // Вопросы мед химии. - 1990. -Т.36,№5. - С. 32-34.
8. Горкин В.З., Овчинникова Л.Н. Система Аминооксидаз: современные достижения в исследовании природы, функций и их нарушений // Вопросы мед химии. - 1993. -Т.39,№4. - С. 2-10.
9. Горкин В.З. Аминооксидазы и их значение в медицине. Москва. - 1981. - 334 с.
10. Горкин В.З. Современные достижения в исследованиях специфического ингибирования и природы МАО (обзор). Вопросы мед химии, 1982. - №2. - С. 2-9.
11. Типтон К.Ф. Ингибиторы МАО и прессорный ответ на пищевые амины // Вопросы мед химии. - 1997. - Т.43,№6. -С. 494-498.
12. Levitt P., Pintar J.E. and Breakefield X.O. // Proc. Natl. Acad. Sci. - 1982. - Vol. 79. - P. 6385-6389.
13. Рамсэй Р. Механистическое исследование по МАО: значение для МАО - А и МАО - В в in situ // Вопросы мед химии. - 1997. - Т. 43, №6. - С. 457-469.
14. Медведев А.Е.. Горкин В.З. Роль моноаминооксидаз в регуляции энергетических функций митохондрий // Вопросы мед химии. - 1991. - Т. 37,№ 5. - С. 2-6.
15. Медведев А.Е., Типтон К.Ф. Окислительная модификация моноаминооксидаз // Вопросы мед химии. - 1997. -Т.43,№6. - С. 417-418.
16. Волошина О.Н., Москвитина Т.А. Способ определения моноаминооксидазной активносоти тромбоцитов // Лабораторное дело. - 1985. - №5. - С. 289.
17. Матлина Э.Ш. Методы исследования некоторых гормонов и медиаторов. Москва. - 1965. - 205 с.
18. Endo Y., Ogura Y. Arapid and simple determination of histamine and polyamines // Japan J. Pharmacol. - 1975.-№ 25. -P. 610-612.
19. Slabo G., Kovaes G.L. Teleqdy G. A modified sereening method for rapid simultaneous determination of dopamine, noradrenaline and serotonin in the same brain region // Acta Physiol. Hung. - 1983. - Vol. 61 (1-2). - P. 51-57.
ENGLISH VERSION: INFLUENCE OF SUBACUTE EXPERIMENT WITH EXCHANGE OLIGOETHERCYKLOCARBONAT IN SUBTOXIC DOSES ON MONOAMINES AND ACTIVE PROCESSES DEAMINATION
Bagmut I.Yu.
Kharkov Medical Academy of Postgraduate Education, Kharkov, Ukraine
Abstract. The effects of small doses of a new sub-toxic chemical substance belonging to polyethers-oiigoethercykiocarbonat type P-803 was investigated n 40 white Wistar rats in the subacute experiment. In the iiver and brain adrenaline, noradrenaline, DOPA, dopamine, serotonin, tryptophanwere rated. DOPA content, dopamine, epinephrine, norepinephrine, serotonin, tryptophan platelet activity and MAO-B were determined as the content of monoamines and plasma. Studies suggest that oligoethercyklocarbonat P-803 in 1/10 and 1/100 LD50 activates processes of oxidative deamination on the background of inhibition ergotropic function at these doses.
Keywords: xenobiotic, adrenaline, noradernalin, DOPA, dopamine, serotonin, tryptophan, blood plasma, liver and brain of rats.
This work is a piece of research KhNMU "Study of mechanisms of biological action of simple polyethers have problems in health circumflex media", state registration number 0110U001812.
Introduction. state. Development of scientific and technological pro-
It has been lately become hard to find a corner of the
gress, human activities continues to create such working
. , . , ..j,. m x . . ... TL and living conditions that limit or narrow the range of ef-
planet which wou|d not bee fected human activities. The fects on the human factors of the natural environment,
proportion of negative impact on the biosphere by Chemh primarily of natural origin-ultraviolet radiation, water bodies,
ra organic synth^, surfaœ-active agents ^rtactanteO, forests, etc. All this isreflected in the resistance and reac-
detergents ( (CMC), pesticides, herbicides, akylatJng tance to the effects of harmful physical, chemical, biologi-
agents, polyether macrocycles and others is signyficant[1]. . , . . , 0. .. . .
' ^ 1 . , .xi- ,j ■ , L cal and socio-environmental factors. Studies suggest that
Over the past decade the world synthesized tens of mil- , . ... .. , ... .. 3f
.. , i . ., . „ , . ,, . ,, . , an adequate qualitative and quantitative impact on the
lions of chemicals that are often highly stable, toxic and u-j. t ■tuu-iin -j
, , ,. . , t-i-i x ..I body's response to negative sources is the basis of full and have a pronounced biotropic and ability to provide long-
r . ■ ■. timely physiologically adaptation to the changes in the hu-
term consequences of their influence: genotoxicity, man environment and the key to the preservation and
mutagenfis, ,carhcin°9enef' terato|genesis,'mmkune df promotion of health. However, long-lasting and negative
ciency, eta Much of the chemical load on the biosphere impact on the body of chemicals n sub-toxic doses can
has created a new environmental situation, which can lead to disruption oof homeostasis, disruption of protective
shape the development of many diseases and pathological and adaptive mechanisms of adaptation and the "develop-
To cite this English version: Bagmut I.Yu. Influence of subacute EXPERIMENT with exchange oligoethercyklocarbonat In subtoxic Doses On monoamines and active processes deamination / /Problemy ekologii ta medytsyny. - 2014. - Vol 18, № 3-4. - P. 61 -63.
Tom 18. N 3-4 2014 p.
ment of pathological conditions. Over the past decade enough information, have gathered which clearly shows the leading role of exchange biogenic monoamines in the formation of diseases of the central nervous system (CNS), cardiovascular system (CVS), mental diseases and cancer, etc. Pathogenic significance of violations of the catalytic activity of monoamine oxidase, which ensure oxidative deamination of primary, secondary and tertiary monoamineshave been noted. Thus, monoamine oxidase (MAO) is maintained at a certain level of physiological content of catecholamines, serotonin, histamine, tryptamine, etc. [2,3,4,5,6,7,8]. Changing the properties of MAO activity and found at many diseases and pathological conditions: irradiation, malignant growth, hypervitaminosis D, cold stress, hypoxia, hypercholesterolemia, traumatic brain injury [9,10,11,12,13,14,15]. In the literature, there is evidence of a direct correlation between the intensity of the exchange of biogenic amines in cellular structures and the degree of activity of the pathological process in different organs. Given the above said current study was aumed at MAO activity and the content of some biogenic mono-amines and their precursors under the influence of sub-toxic doses oligoethercyklocarbonat in various organs and tissues.
Materials and methods
The study used a new chemical substance belonging to polyethers-oligoethercyklocarbonat type P-803. This compound is widely used to produce plastics, foams, ep-oxy resins, lacquers, enamels, polyurethane and others [1]. Selecting this connection justified large volumes of production, extensive contacts with the population and the lack of prognostic characteristics of the potential hazard to humans and warm-blooded animals. On the basis of estimates of the parameters of acute toxicity oligoeth-ercyklocarbonat relates to compounds of low toxicity to non-cumulative properties and species sensitivity. The mean dose (LD50) was set at 18,75 g / kg of animal weight and the ratio of commutation (Kc) at 7,82. The research program included a subacute toxicology experience on mature white Wistar rats weighing 180-200 g in accordance with the conditions of the experiment the
animals every day, in the morning before feeding, for 45 days, with a metal probe were carried out orally with aqueous solutions of substances on the basis of 1/10; 1/100; 1/1000 of LD50. The control group received the appropriate volume of drinking water. The experiment used 40 white rats in compliance with the principles of bioethics and the "European Convention for the Protection of Vertebrate Animals used for research and other purposes"-Strasbourg, 1985 exploration program included the determination of the activity of platelet MAO-B from the rate of the reaction product of deamination-benzaldehyde [16]. Contents of DOPA, dopamine, epi-nephrine, norepinephrine, serotonin, tryptophan in blood plasma was measured by a spectrophotometer spectro-fluorimetric firm "Hitachi"-MNR-4 [17]. In the liver and brain adrenaline, noradrenaline, dOpA, dopamine, serotonin, tryptophan were rated. Studies were carried out by the method of Y. Endo, Y. Odura [18]. To bind biogenic monoamine precursors was used carboxymethylcellulose (CMC) of the firm «Reanal», capacity 0,6-0,8 mEq/h Oxidation of catecholamines and DOPa produced by the method described in G. Slabo et al. [19]. Spectro-fluorimetric determination of levels of biogenic monoamines and their precursors was carried out with a spectrophotometer by "Hitachi" MNR-4 column chromatogra-phy. Quantitative levels were assessed by calibration curves. Statistical processing of the results was carried out using Student's t test, Fisher.
Results and discussion
Studying the influence of exchange of biogenic monoamines in the brain influenced by subtoxic doses of oligoethercyklocarbonat detected improving DOPA-dopamine precursor at 34,27% and 28,16%, respectively, under the influence of 1/10 and 1/100 of LD50. At the same time, a decrease of dopamine at 31,77% and 28,24%, 46,16% for norepinephrine and 19,24%, 69,77% for adrenaline and 34,89%, respectively, in terms of white rats toxification 1/10 and 1/100 of LD50 (Table 1). At a dose of 1/1000 LD50 xenobiotic didnot violate the exchange of monoamines in the brain.
Table 1
Effect of P-803 oligoethercyklocarbonat in subtoxic doses exchange monoamines in the brain in the subacute experiment (mkg/g tissue)
Indicators Monitoring Group, LD50 (M ± m)
Control(n=10) 1/10(n=10) 1/100(n=10) 1/1000(n=10)
DOPA 2,13±0,12 2,86±0,17* 2,73±0,21* 2,25±0,23
Dopamine 3,40±0,37 2,32±0,28* 2,44±0,26* 3,48±0,27
Norepinephrine 0,78±0,06 0,42±0,04* 0,63±0,07* 0,75±0,14
Adrenaline 0,43±0,08 0,13±0,015* 0,28±0,09* 0,45±0,16
Note: * The differences are significant, p<0,05
In marked reduction of liver DOPA, dopamine, norepinephrine and epinephrine oligoethercyklocarbonat influenced in a dose of 1/10 and 1/100 of LD50 (Table 2) Substance 1/1000 of LD50 not disturb the exchange of biogenic monoamines. Thus, it was found to decrease by
Effect of P-803 oligoethertcyklocarbonat exchange monoami
36,80% DOPA and 23,46%, 46,83% for dopamine and 28,39%, 50,62% for norepinephrine and 28,40%, 59,10% for adrenaline and 50,0%, respectively, under the influence of 1/10 and 1/100 of LD50.
Table 2
in subacute experiment in the liver under the influence of sub-toxic
doses (mg/g tissue)
Indicators Monitoring Group, LD50 (M ± m)
Control (n=10) 1/10(n=10) 1/100(n=10) 1/1000(n=10)
DOPA 4,05±0,36 2,56±0,42* 3,10±0,28* 3,85±0,25
Dopamine 1,73±0,19 0,92±0,07* 1,24±0,14* 1,83±0,21
Norepinephrine 0,81 ±0,09 0,40±0,05* 0,58±0,12* 0,78±0,08
Adrenaline 0,22±0,03 0,09±0,002* 0,11 ±0,02* 0,23±0,04
Note: * The differences are significant, p<0,05
Analysis of the results of serotonin metabolism in the liver and found a reduction in brain tryptophan and serotonin levels increase under the influence oligoethercyklocarbonat in 1/10 and 1/100 LD50. (Table 3). Tryptophan in the liver decreased by 72,52% and 47,99% in the brain at
30,53% and 28,34%, respectively, in groups of animals toxification 1/10 and 1/100 of LD50. Thus, in the liver increased serotonin by 228,07%, and 127,36%, and in brains at 119,02% and 62,31%, respectively, under the influence of 1/10 and 1/100 of LD50.
Table 3
Effect of P-803 oligoethercyklocarbonat on serotonin metabolism in the liver and brain influenced by subtoxic doses (mg/g tissue)
Indicators/bodies Monitoring group, LD50 (M ± m)
Control (n=10) 1/10(n=10) 1/100(n=10) 1/1000(n=10)
Liver/try ptophan 13,9±1,25 3,82±0,36* 7,23±0,65* 14,5±1,17
Liver/serotonin 2,85±0,74 9,35±0,78* 6,48±0,54* 3,16±0,26
Brain/try ptophan 5,93±0,82 4,12±0,37* 4,25±0,46* 5,88±0,62
Brain/serotonin 2,68±0,37 5,87±0,42* 4,35±0,36* 2,74±0,28
Note: * The differences are significant, p<0,05
Determination of serum levels of biogenic monoamines revealed a decrease in the level of dopamine, epinephrine, norepinephrine and their precursor DOPA against increase serotonin (Table 4). Activity of thrombocyte monoamine oxidase (MAO-B), was significantly enhanced under the influ-
Effect of P-803 oligoethercyklocarbonata activity platelet
ence of xenobiotic 1/10 and 1/100 of LD50, indicating increased oxidative deamination of these doses. Oligoethercyklocarbonat in 1/1000 LD50 had no impact on the exchange of biogenic monoamines.
Table 4
>-B and the content of monoamines in serum influenced xenobiotic
subtoxic doses.
Indicators Monitoring Group, LD50 (M ± m)
Control (n=10) 1/10(n=10) 1/100(n=10) 1/1000(n=10)
Dopamine (mmol/l) 0,83±0,05 0,52±0,04* 0,63±0,05* 0,86±0,08
Serotonin (mmol/l) 0,29±0,02 0,94±0,08* 0,77±0,06* 0,31±0,05
MAO-B (nmol/mg pro-tein^min.) 0,37±0,04 0,85±0,06* 0,68±0,05* 0,41 ±0,06
Adrenaline (nmol/L) 2,40±0,25 0,46±0,03* 0,62±0,07* 2,30±0,35
Norepinephrine (nmol/L) 2,56±0,19 0,52±0,07* 1,25±0,11* 2,44±0,22
DOPA (nmol/L) 17,80±2,65 5,87±0,62* 8,38±0,76* 15,69±1,85
Note: * The differences are significant, p <0.05
Conclusions.
Thus, studies show that oligoethercyklocarbonat P-803 in 1/10 and 1/100 LD50 activates processes of oxida-tive deamination on the background of inhibition at these doses ergotropic functions of the body, which is associated with increased trophotropic as protective and adaptive response that aimed at ensuring the stability of the internal environment of the body. In 1/1000 LD50 xenobi-otic does not affect the metabolism of monoamines and oxidative deamination.
References
1. Zhukov V.l., Popova L.D., Zaitseva O.V., Kratenko R.I. etc. Simple and macrocyclic ethers: Scientific basis for the protection of water bodies.-Kharkov, Tornado, 2000. - P.-438.
2. Hakobyan A.A., Arutnyan M.V., Agavelyan A.M., Role of monoamine oxidase in the pathology of the colon // Questions honey Chemistry. - 1994.-T. 40, № 6.-P. 54-57.
3. Hakobyan A.A., Promyslov M.S. Monoamine oxidase in the brain cranial injury. // Questions honey Chemistry. -1984.-T.30,№ 1.-P. 75-77.
4. Burchinsky S.G., Kuznetsov S.M. Monoamine oxidase inhibitors and brain in gerontology // Questions honey Chemistry. - 1988.-№ 4.-P. 2-9.
5. Ashmarina I.P., Stupalova P.V. Neurochemistry. Moscow, 1996.-427 p.
6. Goroshinskaya I.A. Role of monoamine oxidase in the body's response to extreme impact. Dissertation for the degree d.b.nauk, Rostov-on-Don, 1998. - 411 p.
7. Kamyshanskaya N.S., Gokin V.Z., Voitenko N.N. Multiple forms of rat brain MAO under extreme catatonia // Questions honey Chemistry. - 1990.-T.36,№ 5.-P. 32-34.
8. Gorkin V.Z., Ovchinnikov L.N., Aminooxidaz system: recent advances in the study of nature, functions and their disorders // Questions honey chemistry.-1993.-T.39,N 4.-P. 2-10.
9. Gorkin V.Z. Aminooxidazy and their importance in medicine. Moscow.-1981. - P.-334.
10. Gorkin V.Z. Recent advances in research and the nature of the specific inhibition of MAO (review) // Questions honey Chemistry. - 1982.-№ 2.-P. 2-9.
11. Tipton K.F. MAO inhibitors and the pressor response to dietary amines // Questions honey chemistry. - 1997.-V.43,№ 6.-P. 494-498.
12. Levitt P., Pintar J.E. and Breakefield X.O. // Proc. Natl. Acad. Sci. - 1982.- Vol. 79.-P. 6385-6389.
13. Ramsay R. Mechanistic study MAO: implications for MAO-A and MAO - B and in situ // Questions honey chemistry. -1997.-T. 43,№ 6.-P. 457-469.
14. Medvedev A.E. Gorkin V.Z. Role of monoamine oxidase in the regulation of mitochondrial energy functions // Questions of medical chemistry.- 1991.-T. 37,№ 5.-P. 2-6.
15. Medvedev A.E., Tipton K.F. Oxidative modification of monoamine oxidase // Questions of medical chemistry. -1997.-V.43,№ 6.-P. 417-418.
16. Voloshin O.N., Moskvitina T.A. A method for determining platelet activity of monoamine oxidase // Laboratory business. - 1985.-№ 5.-P. 289.
17. Matlina E.S. Methods of investigation of certain hormones and neurotransmitters. Moscow.-1965. - P.-205.
18. Endo Y., Ogura Y. Arapid and simple determination of histamine and polyamines // Japan J. Pharmacol.-1975.-№ 25.-P. 610-612.
19. Slabo G., Kovaes G.L. Teleqdy G. A modified sereening method for rapid simultaneous determination of dopamine, noradrenaline and serotonin in the same brain region // Act. Physiol. Hung.-1983.-Vol. 61 (1-2).-P. 51-57.
MaTepian HagitiuooB go pegamiï 02.09.2014
6З
