THE INFLUENCE OF HYDRAZINE DERIVATIVES ON ENVIRONMENT AND LIVING THINGS

Saspugayeva G.Y., Khanturin M.R., Beysenova R.R.

gulnur.er@mail.ru

Eurasian National University named after L.N. Gumilev

 

Introduction. Pollution of environment, connected with intensive industry and, as a result, declination of health of nation – one of the biggest problems of modern age. For Kazakhstan, where Baikonur is situated, problem of environment pollution with rocket fuel and its components is very up-to-date. Results of complex expedition researches of Russia and Kazakhstan, carried out in places of fall of residual parts of space rockets showed the presence of 1,1-nitrozodimetylamine and its oxidation products in soil, water and plants with concentration higher than maximum allowable. Number of authors showed, that in the result of spilling and spreading of such components of rocket fuel as unsymmetrical dimethylhydrazine, its derivatives (dimethylamine,  tetramethyltetrazen, nitrosodimethylamine) and other highly toxic compounds, in the widest territories around polygons plants and animals die, health of population become worth. Very often population uses   the fragments of space rocket for private economic needs, which is the great menace for their health too. However, a lot of questions about such influence are opened till today. [1]

Also in oil deposits of the Republic of Kazakhstan quantity of vanadium in different parts of Prikaspiysky region is changed 0,3 to 300 g/t of oil in the oil of Buzachi peninsula of West Kazakhstan quantity of vanadium as porphyrinic complex can reach 2800 mg/kg [2, 3].

Development of metallurgy of vanadium and metallurgy of alloy steel, growth of usage of oil fuel in power plants and in engineering, increased usage of intraurban transport with diesel engines – all this is connected with possibility

In connection with this, the question about influence of high concentration of vanadium on the organism of human and animal is very up-to-date today.

In our previous researches we found decreasing of crude protein in blood plasma of rats after influence of derivatives of hydrazine and vanadium oxide [5]. This research is directed to clarifying of reasons of this decreasing.

The aim of research was the studying of influence of derivatives of hydrazine and vanadium oxide on redistribution of plasma protein between blood and lymph and change of hemodynamic parameter, caused by this. 

Blood is the main life environment, its quality influence all the processes, proceeding in organs and cells. In defects of blood quality, primarily hemoconcentration, acidulation, increase of cholesterol level and others, the main transport function of blood is made difficult, which leads to defects of redox process in all the organs and tissues, including brain, liver, kidneys, and so on.  Blood quality must be supported in the limits of optimal homeostasis.  

In majority of cases, albumen, circulating in blood, is excreted through kidneys, gasrtointestinal tract and goes to the third space – tissues or serous sac, including pleural sac and abdominal cavity. Decreasing os albumen synthesis by liver cells in the conditions of severe hepatic impairment is the frequent reason of hypoalbuminemia as well. Starvation or poor nutrition cause hypoalbuminemia much more seldom.

Almost always the reason of hypoglobulinemia is the loss of globulin through gasrtointestinal tract; as a rule, in this time albumen is lost as well, and together this causes the progress of panhypoproteinemia.

Also it is known that the reason of thick blood is lack of vitamins and minerals, such as lecitin, vitamin C, zinc, selenium and others, which take part in process of production of hormones and ferments.  Such lack can be resulted by poor work of liver, which is the main biochemical laboratory of organism and needs regular on-time cleaning. This is connected with constant hard work. Especially when we talk about people, who eat canned, smoked, meat, salty and sweet food, and who are under hard labour conditions and poor environment. [3,4].

 

Materials and methods: Blood sampling for biochemical analysis was made in the morning on an empty stomach, from carotid artery. Crude protein in blood plasma and lymph was defined by biochemical analyser Screen Master REF UHD 113 by biuret method with usage of diagnostic kit of “Agat” company. Contractive activity of thoracic duct flow of rats was examined according to common method.  [6]. For isolated smooth muscle preparations of rats there was used Krebs: рН - 7,4 with temperature +37° С. Nutrient solutions oxigenated with gas mixture: 95 % О2 and 5 % СО2. Spontaneous contractive activity was registered in personal computer in program СИ++. All the results of experiments were treated with the usage of criterion of Student [7].

 

Results and discussion: In acute intoxication with nitrosodimethylamine, quantity of crude protein in blood plasma is decreased on 49,05% (P<0,01), in lymph it is increased four times (P<0,001), volume of blood plasma is decreased on 24% (P<0,05). In acute intoxication with isonicotinic acid hydrazide quantity of crude protein in blood is decreased on 42,1% (P<0,01), in lymph it is increased on  51,7% (P<0,001), volume of plasma is decreased on 23,4% (P<0,05). In acute intoxication with phenylhydrazine, crude protein in blood is decreased on 21,02%, in lymph it is increased on 55,4% (P<0,001), volume of plasma is decreased on 29,6% (P<0,01). In acute intoxication with hydrazine sulphate quantity of crude protein in blood is decreased on 26,2% P<0,05), in lymph it is increased on 44,8% (P<0,05), volume of plasma is decreased on 17,3%.

This shows the transition of plasma protein into interstitial tissue, may be it is connected with increasing of permeability of capillary paries and with influence of hydrazine on peptide bonds of polypeptides, which improves the migration of protein particles from blood channel to lymph.  It is known that hydrazines react with all the amino acids, excluding C-terminal amino acid, whose carboxyl group does not participate in organization of peptide bond.

In chronical intoxication with nitrosodimethylamine quantity of crude protein in blood is increased on 21,5%, isonicotinic acid hydrazide - increasing on 58% (P<0,05), phenylhydrazine – increasing on 14,91% (P<0,05), hydrazine sulphate – increasing on 54% (P<0,001). Quantity of crude protein in lymph of animals that were chronically intoxicated by hydrazines was increased in intoxication with NDMA on 72,08% (P<0,01), decreased in intoxication with isonicotinic acid hydrazide on 63,84% (P<0,001), was increased in intoxication with phenylhydrazine on  56% (P<0,001), with hydrazine sulphate it was edged in comparison with control group. It is known that lymphatic system favors the regulation of plasma volume by handing back of proteins from tissues into lymph. With the aim of studying of influence of hydrazine on drainage function of lymphatic system, we carried the experiments with the registration of contractive activity of thoracic duct flow of rats, sacrificed to acute and chronical intoxication with hydrazine derivatives.  

In chronical intoxication of animals with NDMA we can observe decreasing of frequency of spontaneous beating on 17,25% (p<0.001) and decreasing of amplitude of spontaneous beating on 46,39% (p<0.001). These data show, that in intoxication of thoracic duct flow with NDMA, lymph drainage function is suppressed. In chronical intoxication of animals with isoniaside we can observe decreasing of frequency of spontaneous beating on 10,8% (p<0.05) and decreasing of amplitude of spontaneous beating on 21,8% (p<0,001). This decreasing is insignificant, that lets to suggest the insignificant influence of isoniaside on thoracic duct flow. In chronical intoxication of animals with phenylhydrazine we can observe suppression of spontaneous beating of thoracic duct flow: frequency is decreased on 45,5% (p<0.001), and amplitude is decreased on 36,1% (p<0,01). This leads to idea about significant combativeness of this substance onto thoracic duct flow, and, consequently, suppression or stop of lymph flow along the vessel. In chronical intoxication of animals with hydrazine sulphate we can observe decreasing of frequency of spontaneous beating on 54,4% (p<0.001) and decreasing of amplitude of spontaneous beating on 20,7% (p<0,01). This shows the high combativeness of hydrazine sulphate onto thoracic duct flow.

Frequency of beating of thoracic duct flow in chronic primer with isoniaside in response on adrenalin is increased in larger degree in comparison with controlled animals. Amplitude of beating in this group of experimental animals was suppresses in response on adrenalin on 20%.

In 8-group of animals frequency of beating in response on adrenalin in increased in smaller degree and amplitude is lower than level of responses of controlled preparations on 68%. Frequency of beating of thoracic duct flow in chronic primer with phenylhydrazine in response on adrenalin is increased in larger degree in comparison with controlled animals. Amplitude of beating in this group of experimental animals was suppresses in response on adrenalin on  62%.

In 10-group of animals in acute intoxication frequency of beating in the response on adrenalin is increased in smaller degree and amplitude is lower than the level of responses of controlled preparations on 75% . Frequency of beating of thoracic duct flow in chronic primer with sulphur hydrazine in response on adrenalin is increased in larger degree in comparison with controlled animals. Amplitude of beating in this group of experimental animals was suppressed in response on adrenalin on 70%.

            Experiments with vasoactive substance – adrenalin and its antagonists showed that in intoxication with hydrazines there was educed the suppression of contractive activity of thoracic duct flow, and that suppression of this function of duct flow is performed by damage of receptor apparatus of myocyte membrane. Among all the studied derivatives of hydrazine, nitrosodimethylamine and phenylhydrazine showed the greatest influence on duct flow, than hydrazine sulphate, and isoniaside showed the smallest negative effect, but influenced negatively on functions of this vessel. Also our experimental data with usage of adrenergic blockers can show that hydrazines in larger degree suppress α-adrenoreceptors in chronical intoxication, and in the same degree suppress the action of alpha and beta adrenoreceptors in acute intoxication.

So, results of our researches show that contractive activity of thoracic duct flow of animals, which took the different derivatives of hydrazine in both acute and chronical experiment, is suppressed.  According to our data, these changes connected with damage of receptor link of neurohumoral regulation of this vessel. Secondary to action of hydrazine, transport function of thoracic duct flow was suppressed more than on 40%, consequently, protein return from tissues to lymph is decreased. So, amplitude of spontaneous beating of thoracic duct flow was suppressed on 46% in acute and chronical intoxication with NDMA, in other groups we noted the suppression of force of arctation of thoracic duct flow on 20-37%.

Apparently, in action of hydrazines there takes place the increasing of vascular permeability for protein, which can be decided according to decreasing of concentration of crude protein in blood plasma and its increasing in lymph, decreasing of volume of blood plasma by hematocrit. Such significant modifications in level of plasma volume can be the result of blood thickening due to significant decreasing of crude protein in plasma, and, consequently, its increasing in interstitial space.

All written above lets make the conclusion, that under the influence of hydrazine there takes place the accumulation of protein and liquid in interstitial space and in lymphatic system due to suppression of transport ability of lymph vessels, and, as a result, decreasing of concentration of crude protein and liquid in blood, that leads to the blood thickening.

We discovered such modifications in content of crude protein in blood plasma with simultaneous suppression of contractive activity of thoracic duct flow in the action of other toxicants as well – vanadium oxide, mercuric acetate, sodium arsenide, copper sulfate, ferrum sulfate, cobalt sulphate, zinc sulfate [8-10]. Apparently, this is a general mechanism of influence of ecotoxicants on the protein balance of organism.

 

 

 

References

 

  1. Березов Т. Т., Коровкин Б. Ф. - Биологическая химия —Москва, «Медицина»,1990г.
  2. Долгов В. В., Шевченко О. П. - Лабораторная диагностика нарушений обмена белков — Москва, РМАПО, 1997 г.
  3. Камышников В. С. - Карманный справочник врача по лабораторной диагностике — Москва, МЕДпресс-информ, 2007 г.
  4. Медицинская биохимия: Лабораторный практикум под редакцией Семиколеновой Н. А. - Омск, издательство ОмГУ, 2005 г.
  5. Хантурин М.Р., Хантурина Г.Р., Бейсенова Р.Р.Динамика транскапиллярного обмена белков при действии пентаоксида ванадия. Вестник ЕНУ им. Л.Н. Гумилева. Серия естественных и технических наук.- 2008.- № 6 (67).- С.42-46.
  6. Nasirova R.N. The law of distribution of vanadium in petroleum Near-Caspian NGB / the Oil facilities - 1993. 2. p.39-45.
  7. Bakirova S.F., Kotova A.V., Benkovskij V.G.  N.F.Problems of processing heavy oil (petroleum). Alma-Ata, 1980-С.143-151p.

8. Chigarkin A.V. Geoecology of Kazakhstan. Almaty: Сanat, 1995.-160p.

  1. Roschin A.V. Vanadium and its connections. M: Medicine 1968, 200p.
  2. Rsalieva A.K., Khanturin M.R., Akmukasheva S.K., Abdimanova A.T. Research of cytologic, biochemical parameters of blood of laboratory rats at an intoxication of pentaoxide vanadium and on a background of correction by preparation "Salsokollinum" // the Bulletin the Hag. A series biology, medicine, geography.-2005.-¹ 3, (39.-) 27-31p.