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Abdullaeva Mashhura Ikromzhonovna, the basic doctoral student of the Department of Medical and Biological Chemistry Tashkent Medical Academy, Uzbekistan Inoyatova Feruza Hidoyatovna, professor of department of medical and biological chemistry Tashkent Medical Academy, Uzbekistan E-mail: [email protected]
NATURAL NEUROTROPIC AUTOANTIBODIES IN CHRONIC ALCOHOL INTOXICATION
Abstract: Changes in the content of auto-at to antigens from the nervous tissue are likely to indicate pathogenetic changes in the functioning of the immune system and be used as predictors of damage to the nervous system during alcohol intoxication.
Keywords: Neurotropic autoantibodies, psychoactive substances, alcohol intoxication.
The widespread distribution and use of drugs is a significant socio-economic and medical problem. According to WHO, more than 3% of the inhabitants of our planet are addicted to psychoactive substances, including narcotic substances [4]. It is obvious that alcohol addiction is mediated by its effect on the brain. Ethanol and the product of its biotransformation acetaldehyde have a pronounced neurotropic effect. The effect of ethanol on the brain is associated with its ability to penetrate the membrane and alter the physical properties of the lipid components of the membranes, the content and functions of neurotransmitters in the brain, as well as at different stages of nerve impulse transmission [7]. As a consequence, acute ethanol intoxication is characterized by mental, autonomic, neurological disorders and metabolic acidosis.
Recently, laboratory diagnostics, including the definition of neurospecific proteins (NSB), biologically active molecules that are specific for nervous tissue and perform functions characteristic of the nervous system, have attracted more and more attention. Over the past 30 years, more than 60 different brain NSBs have been characterized. They can be classified according to the localization-structural principle (neuronal, glial; membrane-associated and cytoplasmic, etc.), according to their functional role, and they also distinguish the subgroup ofNSBs present in normal conditions and in pathologies [2]. Determining the level ofNSB contributes to early diagnosis, because significant changes in their concentration often occur earlier than the damage that can be detected by instrumental examination methods. In addition, they allow an assessment of the prognosis of the course and outcome of the disease, and monitoring ofthe treatment ofpatients. Numerous studies have shown their increase in schizophrenia, traumatic brain injury, acute and chronic disorders of cerebral circulation, epilepsy, Alzheimer's disease, multiple sclerosis, etc. [5; 8]. In the literature, there are conflicting single messages on the content of NSB in the serum during alcohol intoxication.
Objective: to determine the concentration of natural neurotropic autoantibodies in the serum of rats during chronic alcohol intoxication.
Material and methods. The experiments were conducted on 48 Wistar male rats weighing 130-150 g. Simulation of chronic alcohol intoxication in rats was performed according to Liber C. S., DeCarli L. M. Animals of the experimental group received ad libitum liquid diet, 36% of the energy value of which was provided by ethanol. In the control isocaloric diet, ethanol was replaced by the carbohydrate component of the diet. Control animals were injected with saline intra-peritoneally at a dose of 0.3 ml/100 g. The duration of the experiment was 4 weeks. Studies were conducted on the 7th, 14th, 21st and 28th day from the beginning of the experiment.
The content of neurotropic auto-AT, directed to proteins: neurofilament protein-200 (NF-200), glial fibrillary acidic protein (GFAP), S-100, the main myelin protein (MBP), voltage-dependent Ca channel (VGCC) in serum was determined with the help of ELI-N-Testa IIC "Immunculus", Moscow. Isolation of protein-antigens was performed according to the method of A. B. Poletaeva et al. [7]. Data on serum immunoresistance of the analyzed samples, obtained in absolute units of optical density, were converted into conventional units (UE) [6]. Digital material processed by the method of variation statistics. To study the relationship between the parameters studied, a correlation analysis was performed in the program Statistica 6.0.
Results and discussion. It is known that the clinical manifestations of alcohol intoxication are characterized mainly by disorders in the nervous system [10]. At the same time, an important role in the pathogenesis of many diseases is played by autoimmune mechanisms. The results of the determination of neurotrophic auto-AT in the serum of rats under the conditions of modeling chronic alcohol intoxication are shown
Section 2. Medical science
in Table 1. As follows from the data presented in the table, the chronic effects of ethanol during the 1st week revealed differences in the levels of auto-AT to different nerve tissue proteins relative to intact rats. So, if the content of auto-AT in the serum to GFAP, S-100 and VGCC significantly increased by 43.8; 31.4 and 47.2%, then NF-200 and MBP had only a tendency to increase. As the length of the introduction of ethanol lengthened, the content of auto-AT to NSB in the serum of experimental animals gradually increased significantly. The greatest changes were revealed by the final date of the introduction of the toxicant, which was manifested by a significant
Table 1. - The content of neurotropic autoantibodies in
increase in their content: to NF-200, GFAP, S-100 MBP and VGCC significantly increased by 130.9; 182.8; 152.2; 54.2 and 121.7% relative to the values of intact rats. As can be seen from the above data, the content of auto-AT to NBC progressively increases as alcohol dependence worsens, this is more pronounced for NB-200 such as NF-200, GFAP, S-100 and VGCC and a lesser degree for MBP.
As can be seen from the above data, the content of auto-AT to NBC progressively increases as alcohol dependence worsens, this is more pronounced for NB-200 such as NF-200, GFAP, S-100 and VGCC and a lesser degree for MBP.
the serum of rats with chronic ethanol poisoning, M ± m
Groups and study dates NF-200 GFAP S-100 MBP VGCC
Intact 5.272 ± 0.373 3.878 ± 0.288 5.208 ± 0.892 14.836 ± 0.695 2.448 ± 0.232
2nd week 8.673 ± 0.703 7.852 ± 0.387 9.434 ± 0.506 18.692 ± 0.491 4.558 ± 0.307
3rd week 11.122 ± 0.352 10.544 ± 0.495 12.708 ± 0.35 22.582 ± 0.44 5.816 ± 0.155
4th week 14.762 ± 0.653 15.769 ± 0.663 17.262 ± 0.552 25.196 ± 0.637 7.993 ± 0.506
Note: * - the differences between the indices of the intact and
To date, the effects of ethanol have been established for GABA-, glutamate, including NMDA receptors, 5-HT3-sero-tonin and nicotine cholinergic receptors, as well as for voltage-dependent calcium channels and rectifying potassium channels directed inward [1]. However, as shown by our research, the list of neurospecific proteins modified by alcohol is not limited to this list. The studies revealed a more pronounced intensity of autoimmune reactions during alcohol intoxication, as evidenced by a significant increase in the concentration of auto-antibodies to NF-200, S-100, GFAP, MBP, VGCC.
It should be noted that the NF-200 specific axon protein and upward abnormal levels of auto-AT to NF-200 may indicate with high probability that degenerative changes in axons, including their myelin sheaths (demyelination). Our results are consistent with other authors, who also observed an increase in auto-AT to NF-200 in diseases that are accompanied by neurodegenerative processes (schizophrenia, neurosyphilis, epilepsy) [1]. Protein S-100 is a Ca-dependent regulator of many functions (regulation of apoptosis, regulation of neurogenesis, trophic factor of serotonergic neurons). Depending on the concentration, S-100 proteins have a trophic or toxic effect on neurons and glial cells. They act as mediators in the interaction of glia and neurons and, in general, as one of the nodal molecular components of complex intracellular systems that provide functional homeostasis of brain cells, the appearance of auto-AT to S-100 protein is a sign of changes in the CNS associated with emotional disorders, as well as reflects destructive changes in nervous tissue [6]. In this regard, the increase in the serum concentration of auto-AT to the S-100 protein revealed by us confirms and convincingly indicates the progression of changes in
erimentalgroups are significant, P < 0.05.
the nervous system. An increased level of auto-AT to S-100 protein indicates changes in the structures of the central nervous system, which register emotional status, transduction of signals that control the activity ofenergy metabolism enzymes in brain cells, calcium homeostasis, cell cycle, cytoskeleton functions, cell proliferation and differentiation, their mobility, secretory processes, the structural organization ofbiomembranes. It is important to note that S-100 protein is the most specific protein in the brain tissue and the constancy of its concentration ensures the normal functioning of all brain systems. An increase in its level occurs when the glial cells of the brain are damaged and the BBB permeability increases. And also, an increase in aAT to GFAP, MBP, VGCC indicates the aggravation of changes in the brain during alcohol intoxication. An increase in auto-AT to the B-dependent Ca-channel is characteristic of cerebellar ataxia, amyotrophic lateral sclerosis, etc. An increase in the content of auto-AT to GFAP will be associated with dystrophic processes in astrocytes. In addition, this increase may indicate a violation of the barrier function of the BBB. Upward deviations in the content of auto-AT to MBP and NF-200 may, with high probability, indicate degenerative changes in axons, including their myelin sheaths (demyelination). The highest serum concentrations of GFAP were found in neurolepsy. purulent meningitis, febrile schizophrenia, encephalitis, Alzheimer's disease, multiple sclerosis, strokes, open head injury and other critical conditions associated with impaired blood-brain barrier. In addition, the mechanism of the damaging effect of ethanol is the activation of free radical processes. With alcohol intoxication, there is an increase in free radical processes and an increase in the formation ofMDA. These processes are activated by increasing
the duration of the introduction of the toxin. The enhancement of free-radical processes leads to an increase in BBB permeability and the formation of auto-at to NSB and neurotransmitters.
Thus, the results of the performed studies show the dependence of the severity of autoimmune reactions of the majority of the studied neutropic autoantibodies on the chronic effects of alcohol intoxication. At the same time, chronic effects of ethanol are accompanied by changes in opioidergic, adenosinergic, GABAB-ergic, glycinergic and other systems, as well as signal transduction processes (secondary and tertiary messengers). The processes of membrane destruction in brain tissue during alcohol intoxication can be viewed from the standpoint of autoimmune disorders. Changes in the content of auto-at to antigens from the nervous tissue are likely to indicate pathogenetic changes in the functioning of the immune system and be
used as predictors of damage to the nervous system during alcohol intoxication. Therefore, alcohol intoxication is accompanied by damage and death of neurons, astrocytes, oligodendrocytes and microglia. Ethanol, acetalde-hyde and its adducts are the trigger of these violations. A unfolded chain of interrelated pathological processes arises - the release of NSB, which entails the loss of tolerance of the immune system to the antigen of the brain and the development of autoimmune reactions.
Conclusion:
1. The dependence of the severity of autoimmune reactions to NF-200, GFAP, S-100 MBP and VGCC proteins on the duration of intoxication with ethanol was established.
2. The results indicate that alcohol intoxication is accompanied by damage and death of neurons, astrocytes, oligoden-drocytes and microglia.
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