Research shows that autism and other nervous disorders are being diagnosed more and more often today. The reason for this may be not only hereditary genetic diseases, but also dangerous chemicals. In particular, organophosphates alone, used in agriculture, seriously affect the state of the central nervous system.

And recently, experts identified 10 chemicals, so-called neurotoxins, found both in the environment and in household items, furniture and clothing. According to scientists, these substances are the cause of the development of diseases that affect the nervous system. Most of them are already severely limited in use, but some of them still pose a great danger.

Chlorpyrifos

A common chemical in the past, part of the group of organophosphate pesticides, used to kill pests. Currently, chlorpyrifos is classified as a highly toxic compound, hazardous to birds and freshwater fish, and moderately toxic to mammals. Despite this, it is still widely used in non-food crops and for processing wood products.

Methylmercury

Methylmercury is a dangerous neurotoxin that affects the mechanisms of heredity in humans. It causes abnormal mitoses (K-mitoses) in cells and also damages chromosomes, and its effect is 1000 times greater than that of colchicine. Scientists believe it is possible that methylmercury can cause birth defects and mental defects.

Polychlorinated biphenyls

Or PCBs, are part of a group of chemicals defined as persistent organic pollutants. They enter the body through the lungs, gastrointestinal tract with food or skin, and are deposited in fats. PCBs are classified as a probable human carcinogen. In addition, they cause liver disease, disrupt reproductive function and disrupt the endocrine system.

Ethanol

As it turns out, ethanol is not an environmentally friendly alternative to gasoline. Judging by data from scientists from Stanford University, cars using a mixture of ethanol and gasoline contribute to an increase in the level of two carcinogens in the atmosphere - formaldehyde and acetaldehyde. In addition, when using ethanol as fuel, the level of atmospheric ozone will increase, which, even at low concentrations, leads to all kinds of lung diseases.

Lead

Penetrating into the body, lead enters the bloodstream, and is partially excreted naturally, and partially deposited in various systems of the body. With a significant degree of intoxication, disturbances in the functional state of the kidneys, brain, and nervous system develop. Poisoning with organic lead compounds leads to nervous disorders - insomnia and hysteria.

Arsenic

Industrially, arsenic is used to make fertilizers, chemically treat wood, and make semiconductors. Arsenic enters the human body in the form of dust and through the gastrointestinal tract. With prolonged contact with arsenic, malignant tumors can form, in addition, metabolism and the functions of the central and peripheral nervous system are disrupted.

Manganese

First of all, manganese enters the human body through the respiratory tract. Large particles rejected by the respiratory tract can be swallowed along with saliva. Excessive amounts of manganese accumulate in the liver, kidneys, endocrine glands and bones. Intoxication over several years leads to disruption of the central nervous system and the development of Parkinson's disease. In addition, excess manganese leads to bone diseases and increases the risk of fractures.

Fluorine

Although fluoride is widely used in oral hygiene to combat bacterial dental diseases, it can cause many negative effects. Consumption of water containing fluoride at a concentration of one part per million causes changes in brain tissue similar to Alzheimer's disease. The most paradoxical thing is that an excess of fluoride has a destructive effect on the teeth themselves, causing fluorosis.

Tetrachlorethylene

Or perchlorethylene is an excellent solvent and is used in the textile industry and for degreasing metals. On contact with open flames and heated surfaces, it decomposes producing toxic fumes. With prolonged contact, tetrachlorethylene has a toxic effect on the central nervous system, liver and kidneys. A number of acute poisonings leading to death are known.

Toluene

In the chemical industry it is used for the production of benzene, benzoic acid and is part of many solvents. Toluene vapors penetrate the human body through the respiratory tract and skin. Intoxication causes disturbances in the development of the body, reduces learning abilities, affects the nervous system and reduces immunity.

Neurotoxins are substances that inhibit the function of neurons. Neurons are present in the brain and nervous system. The functions of these unique cells are critical to a variety of tasks, ranging from autonomic nervous system actions such as swallowing to higher-level actions carried out by the brain. Neurotoxins can act in a variety of ways and therefore the associated hazards vary depending on the type of neurotoxin and its dose.

In some cases, neurotoxins simply severely damage neurons so that they cannot function.

In other cases, they attack the signaling abilities of neurons, blocking the release of various chemicals or interfering with the process of receiving transmitted messages, and sometimes by causing neurons to send false signals. Neurotoxins can also completely destroy neurons.

Neurotoxin production

In fact, the body itself produces certain neurotoxins. For example, large amounts of many of the neurotransmitters produced to send messages throughout the nervous system can cause harm to the body. In some cases, the body produces neurotoxins in response to a threat to the immune system. Numerous neurotoxins are also present in the natural environment; they are produced by poisonous animals; Heavy metals such as lead are also neurotoxins. Sometimes neurotoxins are used by the authorities of some countries to counter riots and wage war. Neurotoxins used for such purposes are commonly referred to as nerve agents.

Exposure to neurotoxins

Exposure to neurotoxins can cause dizziness, nausea, loss of motor control, paralysis, blurred vision, seizures and stroke. In severe cases, the effects of poisoning can include coma and eventual death due to shutdown of the nervous system. In particular, the body begins to rapidly break down when neurotoxins suppress the function of the autonomic nervous system, as a number of important tasks cease to be performed.

Poisoning

In acute poisoning, the victim is suddenly exposed to a specific dose of neurotoxin. An example of acute poisoning is a snake bite. Chronic poisoning involves slow exposure to a neurotoxin over a period of time. An example of chronic poisoning is heavy metal poisoning, in which the victim unwittingly receives small amounts of a neurotoxin every day.

The problem with heavy metals is that they accumulate in the body rather than being removed from it, so at some point the affected person becomes ill.

A number of techniques can be used to treat neurotoxin poisoning. Many of them rely on supportive care to make it possible to perform tasks that the body cannot cope with until the patient's condition has stabilized. If this occurs, the patient may recover, but will often have to deal with poison-related side effects later. In some cases, chemicals are used to block the function of neurotoxins or flush them out of the body. In other cases, there may be no cure for poisoning, and the goal of treatment is to ensure the patient's comfort.

Source: wisegeek.com
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Neurotoxicity is the ability of chemicals, acting on the body, to cause disruption of the structure or functions of the nervous system. Neurotoxicity is inherent in most known substances.

Neurotoxicants include substances for which the sensitivity threshold of the nervous system (its individual histological and anatomical formations) is significantly lower than other organs and systems, and the basis of intoxication is damage to the nervous system.

Classification of OHTV neurotoxic effects:

1. OTB causing predominantly functional disorders of the central and peripheral parts of the nervous system:

Nerve action OVTV:

Acting on cholinoreactive synapses;

Cholinesterase inhibitors: FOS, carbamates;

Presynaptic blockers of acetylcholine release: botulinum toxin.

Acting on GABA - reactive synapses:

GABA synthesis inhibitors: hydrazine derivatives;

GABA antagonists (GABA-lytics): bicyclophosphates, norbornane;

Presynaptic blockers of GABA release: tetanotoxin.

Blockers of Na – ion channels of excitable membranes:

Tetrodotoxin, saxitoxin.

OVTV of psychodysleptic action:

Euphorigens: tetrahydrocannabinol, sufentanil, clonitazene;

Hallucinogens: lysergic acid diethylamide (LDA);

Deliriums: produced by quinucledin benzilate (BZO phencyclidine (sernyl).

2. OTB causing organic damage to the nervous system:

Thallium; - tetraethyl lead (TEP).

Table 6.

Toxicity of some poisonous substances

Name	Damage through the respiratory system
	LCt50 g min/m 3	ICt50 g min/m 3

Most industrial toxicants, pesticides, and medicines (the use of which is possible as sabotage agents) occupy an intermediate position between deadly toxic substances and temporarily incapacitating ones. The difference in the values ​​of their lethal and incapacitating doses is greater than that of representatives of the first subgroup, and less than that of representatives of the second.

Poisonous and highly toxic nerve agents

Acting on cholinoreactive synapses, cholinesterase inhibitors

Organophosphorus compounds

Organophosphorus compounds have found use as insecticides (chlorophos, karbofos, phosdrin, leptophos, etc.), drugs (phosphacol, armin, etc.), the most toxic representatives of the group are adopted by the armies of a number of countries as chemical warfare agents (sarin , soman, tabun, Vx). OPCs can affect people during accidents at their production facilities, when used as chemical agents or sabotage agents. FOS are derivatives of pentavalent phosphorus acids.

All FOS, when interacting with water, undergo hydrolysis to form non-toxic products. The rate of hydrolysis of OPCs dissolved in water is different (for example, sarin hydrolyzes faster than soman, and soman faster than V-gases).

FOVs form zones of persistent chemical contamination. Those arriving from the contaminated zone who are affected by FOV pose a real danger to others.

Toxicokinetics

Poisoning occurs when inhaling vapors and aerosols, absorbing poisons in liquid and aerosol states through the skin, mucous membranes of the eyes, with contaminated water or food - through the mucous membrane of the gastrointestinal tract. FOVs do not have an irritating effect at the site of application (mucous membranes of the upper respiratory tract and gastrointestinal tract, conjunctiva of the eyes, skin) and penetrate the body almost imperceptibly. Low toxic OPs are capable of relatively long persistence (karbofos – a day or more). The most toxic representatives, as a rule, quickly hydrolyze and oxidize. The half-life of sarin and soman is about 5 minutes, Vx is slightly longer. Metabolism of FOS occurs in all organs and tissues. Only non-toxic metabolites of substances are released from the body and therefore exhaled air, urine, and feces are not dangerous to others.

in biochemistry

Mechanism of action of snake venom neurotoxins

Introduction

chemistry snake venom

Snake venoms are a unique group of biologically active compounds in their chemical composition and physiological effects. Their toxic and medicinal properties have been known to mankind since ancient times. For a long time, interest in the study of these poisonous products was limited to the needs of medical practice. Most of the work was devoted to describing the clinical picture of poisoning, finding methods of specific and nonspecific therapy, as well as the use of snake venoms and their preparations as therapeutic agents. The rational use of snake venoms in medicine is impossible without experimental study and theoretical justification of the essence of the reactions that develop in the body in response to the introduction of a particular poison. The study of individual mechanisms of action of snake venoms on the body is necessary to create scientifically based treatment methods.

Insufficient knowledge about the mechanisms of the toxic action of snake venoms often does not allow doctors to quickly and effectively alleviate the condition of the victim. In some cases, only the external picture of poisoning is taken into account, and clinical care is limited to symptomatic means without taking into account the specific effects of the poison on the vital systems of the body.

It should be noted that snake venoms have a strong toxic effect only in lethal and sublethal doses. Small doses do not cause any clinical manifestations of poisoning and have long been used in practical medicine. However, therapeutic application is often carried out empirically without sufficient theoretical justification, which entails errors. There is no need to prove that the effective use of snake venoms in the clinic should be based on deep knowledge of their composition and properties and, first of all, on experimental studies that should reveal the physiological nature and mechanisms of action of these poisonous substances and help doctors scientifically use venoms for therapeutic purposes. In research laboratories, there has been a sharp increase in interest in zootoxins, and in particular in snake venoms, in connection with obtaining from them in pure form a number of components that have highly specific effects and certain biological structures.

The purpose of this work is to highlight the current state of experimental study of snake venoms, to reveal the mechanisms of pathophysiological effects on the most important functional systems of the body.

State of the chemistry of snake venoms.

Preparation of poisons and its physicochemical properties.

The simplest way to obtain poisonous secretions from snakes is mechanical massage of the poisonous glands. Nowadays, electric current stimulation is often used instead of mechanical massage.

Electrical stimulation is not only a more gentle method of collecting poison, but also allows you to obtain a larger amount of it. The amount of poison obtained from one individual depends on the size of the snake’s body, its physiological state, the number of repeated doses of poison, as well as on a number of environmental conditions. It should be noted that keeping snakes in captivity affects not only the amount of poison obtained, but also its toxicity. Thus, in cobra venom, a decrease in toxicity is observed after six months of captivity. The poison of the viper changes its toxicity only after 2 years of keeping in the nursery. As for small snakes (viper, copperhead, eph), keeping them in serpentariums throughout the year does not affect the properties of the poisons. Freshly extracted snake venom is a slightly opalescent, viscous, fairly transparent liquid; the color of the venom varies from light yellow to lemon.

The active reaction of poisons is usually acidic. Aqueous solutions of them are unstable and lose toxicity after a few days. They become much more resistant to environmental factors after drying over calcium chloride or lyophilization. The poisons are quite thermostable and can withstand heating up to 120 degrees Celsius in an acidic environment without loss of activity. Chemical reagents have a destructive effect on poisons: KMnO 4, ether, chloroform, ethanol methylene blue. Physical factors also influence: UV irradiation, x-rays. Chemical analysis shows the presence of both organic and inorganic substances in snake venoms. According to modern concepts, the toxic activity and biological properties of snake venoms are associated with their protein components.

The main stages of studying the chemical composition and structure of toxic polypeptides of snake venoms. Questions about the chemical nature and mechanisms of action of snake venoms have attracted the attention of researchers. In early studies, the toxic effect was associated with the activity of enzymes present in poisons. Currently, the generally accepted point of view is that the main toxic properties are determined by non-enzymatic polypeptides, along with which poisons contain powerful enzyme systems, the nature and specificity of the action of which in most cases determines the uniqueness of the integral picture of poisoning. Achievements and successes in the field of studying the chemical composition of poisons are closely related to the development and improvement of methods for fractionation and purification of complex mixtures of high molecular weight compounds. Until the 1960s, the study of poisons mainly used dialysis through semipermeable membranes and electrophoretic separation. The development of methods of gel filtration, ion exchange chromatography, ultracentrifugation, as well as the development and automation of methods for analyzing the primary structure of macromolecules made it possible to decipher the sequence of amino acid residues of toxic polypeptides of most snakes in a relatively short time.

1.Terminology and classification of toxic polypeptides

chemistry snake venom

Until recently, there were terminological difficulties when attempting a comparative analysis of the functional and structural features of various non-enzymatic toxic polypeptides of snake venoms. This mainly concerns polypeptides isolated from the venom of snakes of the Elapidae family. At the first stages of studying the chemical composition of poisons, such difficulties were inevitable and were explained by the insufficient degree of purification of individual polypeptides, which in most cases made it difficult to determine the specific nature of their action. As a result, different authors gave different names to polypeptides that turned out to be extremely close, and sometimes identical, in their chemical structure and pharmacological effects. In particular, a group of cardiotoxins was designated as a factor that depolarizes skeletal muscles; toxin Y; direct lytic factor - PLF; cobramines A and B; cytotoxins 1 and 2.

Some authors, when choosing a name, were based on pathophysiological effects (cardiotoxin, PLP, cytotoxin), others emphasized some chemical properties of the polypeptide, for example, its basic character (cobramin), while others assigned a numerical or letter designation to the fraction. Only in recent years has a close similarity in the chemical structure of these polypeptides been established. Evidence has been obtained that hemolytic, cytotoxic, cardiotoxic and other types of activity are inherent in most of these toxins. Therefore, a group of basic polypeptides that do not have specific neurotoxic activity, but effectively act on biological membranes, were called membrane-active polypeptides (MAP).

Based on a comparative analysis of the primary structure and physiological action, which showed the great similarity of neurotoxic polypeptides to each other, they were united under the common term - neurotoxin. Thus, all toxic polypeptides that do not have enzymatic properties and according to their mechanism of action have been isolated so far from the venom of snakes of the family Elapidae and are divided into three groups. The first group includes polypeptides that selectively and specifically block cholinergic receptors of the subsynaptic membrane of the neuromuscular junction - postsynaptic neurotoxins (post-NT). The second group is represented by polypeptides that act selectively on the presynaptic endings of myoneural synapses and disrupt the process of acetylcholine release - presynaptic neurotoxins (pre-NTs).

The third group includes polypeptides that actively affect the membrane structures of cells, including excitable ones, causing their depolarization - membrane-active polypeptides (MAP).

2. Chemistry of postsynaptic neurotoxins

Despite the fact that post-NTs isolated from cobra venom are similar in their pharmacological properties, from the point of view of chemical structure they can be divided into two types.

Type 1 includes post-HT, which is a simple polypeptide chain consisting of 60-62 amino acid residues having 4 disulfide bridges (Fig. 1. A) and having basic properties, a molecular weight of about 7000 (post-HT-1).

Type 2 includes post-NT, consisting of 71-74 amino acid residues, having 5 disulfide bridges (Fig. 1, B), molecular weight of about 8000 (post-NT-2).

Fig 1. Primary structure of neurotoxin II (A) and neurotoxin I (B) from the venom of the Central Asian cobra

Post - NT-1 are built from 15 common amino acid residues; as a rule, Ala, Met and Phen are absent in their composition. On the contrary, post-HT-2 alanine occurs. An interesting feature of the Central Asian cobra venom is the presence of both types of neurotoxins in it. Moreover, in the neurotoxin containing 73 amino acid residues, Arg or Lys 51, characteristic of all post-HT-2, are replaced by Glu.

The saturation of post-HT 1 and 2 disulfide bonds suggests their important functional significance in maintaining the biologically active conformation of the molecule. Reduction of disulfide bonds leads to a loss of 92% of the activity of post - NT-1 and 50% of post - NT-2. re-oxidation restores the original activity of the neurotoxins. Apparently, the greater resistance of post-NT-2 to chemical influences is due to the presence of a fifth disulfide bond, stabilizing a portion of the polypeptide chain. At the same time, in post-NT-1 this same section of the molecule is the most elongated and lacks disulfide bridges. The presence of bridges determines the resistance of post-LT to thermal effects. Thus, in an acidic environment, post-NT can withstand heating to 100°C for 30 minutes without noticeable loss of activity or treatment with 8M urea for 24 hours, but is inactivated by alkalis.

Deciphering the primary structure of neurotoxic polypeptides made it possible to raise the question of the localization and structure of the active center of the molecule that interacts with the choline receptor. The study of the structure of these polypeptides indicates the presence of both α and β structures in the neurotoxin molecules. The central part of the post-HT-1 molecule, free of disulfide bonds, may have greater α-helicality. In addition, the hydrophilic nature of most of the side chains of amino acid residues that make up the sequence from positions 24-25 to positions 39-40 may cause the projection of this loop to the outer side of the molecule, so it is possible that the active center is localized in this region.

Analysis of the location and chemical modification of invariant amino acids found in homologous neurotoxins in the same regions is important. These amino acids, preserved during evolution in identical parts of the polypeptide chain, can participate in the organization of the active center or ensure the maintenance of the active conformation of the molecule. The presence of constant amino acids requires the presence of an invariant triplet gene code in the DNA molecule necessary for the synthesis of a given amino acid sequence.

Since the target for post-HT, as well as for acetylcholine, is the cholinergic receptor, the apparently active sites of neurotoxins should be similar to the quaternary ammonium and carbonyl groups of acetylcholine. It was found that free amino groups, including N-terminal ones, are not obligate to provide toxic activity. Acytylation of 6 amino groups in the neurotoxin from the venom of the Thai cobra led to the loss of 1/3 of the activity.

It could be assumed that the carbonyl groups of the peptide composition, always present in the post-HT molecule, may be important in ensuring toxicity. However, they are inaccessible in the reaction of interaction with the receptor. To a greater extent, the side groups of the side chains of invariant aspartic acid and asparagine meet this requirement. Modification of aspartic acid with glycine methyl ester results in a loss of activity of 75% of the original value.

Irreversible binding between post-NT and the cholinergic receptor cannot be explained solely by the interaction of guanidine and carbonyl groups of post-NT with the corresponding sites of the receptor. Their interaction should be mainly electrostatic in nature, however, the receptor-toxin complex does not dissociate in concentrated saline solutions. Probably these two functional groups serve as “recognition sites” during the initial contact of the post-NT and the receptor. The final irreversible binding is determined by protein-protein interaction, which already includes other areas of the post-HT and cholinergic receptor.

3. Chemistry of presynaptic neurotoxins

The second group of neurotoxins, presynaptic neurotoxins (pre-NTs), are rarely found in snake venoms. Only some of them have been isolated in purified form and studied. In the family Elapidae, presynaptic NTs are found in the venom of the Australian taipan - typoxin, of the Australian tiger snake - notexin, and in the venom of the krait - β-bungarotoxin. Crotoxin, a neurotoxin from rattlesnake venom, has a predominant presynaptic effect on neuromuscular junctions in amphibians and a postsynaptic effect in mammals. Unlike post-HT neurotoxins of group 2, they are built from a larger number of amino acid residues and, accordingly, have a larger molecular weight. In addition, some of them are complexes consisting of subunits.

One of the first pre-NTs obtained using zone electrophoresis on a starch gel and subsequently purified by chromatography on KM-Sephadex with repeated rechromatography was β-bungarotoxin. β-bungarotoxin is built from approximately 179 amino acid residues, among which aspartic acid (22 residues), glycine (16), lysine (13), arginine (14), tyrosine (13) predominate. The presence of 20 cystine residues indicates that the β-bungarotoxin molecule is stabilized by at least 10 sulfide bonds. The molecular weight of the neurotoxin is 28500.

It was assumed that β-bungarotoxin lacks enzymatic properties and is homogeneous. However, it was established that β-bungarotoxin consists of two subunits with molecular weights of 8800 and 12400, and by studying the effects of β-bungarotoxin on oxidative phosphorylation in the mitochondria of nerve endings, they came to the conclusion that the toxin has phospholipase activity.

Notexin was obtained by ion exchange chromatography in an ammonium acetate gradient. The main neurotoxic component of notexin, constituting 6% of the crude, unrefined venom, was isolated in the form of a preparation containing 27% notexin by repeated chromatography.

4. The effect of poisons on neuromuscular transmission

The mechanism of disruption of the transmission of excitation in the myoneural synapse under the influence of snake venoms has been most studied. Already the first observations of the picture of the death of a poisoned animal, which was dominated by symptoms of paralysis of the skeletal and respiratory muscles, necessitated the study of this phenomenon under strict laboratory conditions. Numerous experiments on isolated neuromuscular preparations have shown that snake venoms block the transmission of excitation from nerve to muscle, reduce excitability to direct and indirect stimulation and cause depolarization of nerve and muscle membranes.

Inhibition of neuromuscular transmission under the influence of poison can be realized through two mechanisms. One of them is associated with the blocking effect of the poison on the end plate. The second is based on a depolarizing effect on excitable membranes. However, when using whole venom, it is difficult to differentiate these two mechanisms, since its depolarizing effect leads to blocking of propagating excitation in nerve fibers, and in high concentrations the venom causes muscle contracture. The venom prevents the depolarizing effect of acetylcholine on isolated muscles, while acetylcholinesterase compounds reduce its blocking effect.

In experiments, crotoxin blocked muscle contraction due to indirect stimulation and had no effect on membrane potential. However, studies of the effect of poisons of two varieties (with and without crotamine) reported a practically irreversible blocking effect on neuromuscular transmission in cats and rats of poison without crotamine, both on muscle membranes and on specific receptors of the postsynaptic membrane. Neuromuscular block under the influence of poison containing crotamine was achieved by depolarization of muscle membranes. Viper venom is also capable of disrupting neuromuscular transmission, causing peripheral paralysis due to irreversible blockade of specific acetylcholine receptors. It also inhibits the electrical activity of muscle fibers. Immunochemical analysis showed the presence in the venom of a protein fraction similar to the postsynaptic α- toxin from the venom of the black-necked cobra.

At the Institute of Bioorganic Chemistry named after. Academicians M.M. Shemyakina<#"justify">5. Postsynaptic neurotoxins (post-NT)

Unlike whole cobra venom, post-NTs selectively block the transmission of excitation in the neuromuscular junction without affecting the electrical properties of the nerve and muscle. Incubation of isolated neuromuscular preparations for an hour in a solution containing post-NT at a concentration of about 1 μg/ml leads to a progressive decrease in the amplitude of the end plate potential (EPP). The inhibitory effect increases with increasing stimulation frequency; at the same time, the amplitude of EPPs decreases without significant changes in their frequency. Even at high concentrations, post-NT had no effect on the resting potentials of both muscle and motor terminals.

The cholinergic receptor membranes of the skeletal muscles of vertebrates are most sensitive to the effects of post-NT. At the same time, the somatic muscles of marine mollusks and the heart of the lamprey are resistant to the action of cobra neurotoxins. Species differences in the sensitivity of cholinergic receptors in various representatives of vertebrates (frogs, chickens, kittens, rats). It has been suggested that post-NTs are not direct competitors of acetylcholine for the active site of the cholinergic receptor.

6. Presynaptic neurotoxins (pre-NT)

Neurotoxins with a presynaptic nature of action selectively affect the mechanism of acetylcholine release without affecting the sensitivity to the mediator of postsynaptic structures. Processing of isolated neuromuscular preparation β- bungarotoxin after an initial period of increasing frequency leads to complete elimination of PEP. The rate of onset of the inhibitory effect depends on both the concentration of pre-NT and the frequency of stimulation. The dependence of the time of onset of neuromuscular transmission block on ambient temperature was also established. Thus, typoxin (1 μg/ml) at a temperature of 37 °C caused inhibition of the drug for an hour; when the temperature decreased to 28 °C, conductivity remained until 4 hours of incubation. Pre-NTs do not reduce the response of isolated muscles to exogenous acetylcholine and do not affect the conduction of excitation along nerve terminals. Other evidence of selective presynaptic action β- bungarotoxin were obtained on a nerve-deprived tissue culture obtained from myoblasts of 10-day-old chicken embryos. Pre-incubation α- bungarotoxin completely eliminated the depolarization caused by the subsequent introduction of acetylcholine into the medium. Under these conditions β- bungarotoxin was not effective. In the later stages of action β- bungarotoxin, destruction of vesicles with acetylcholine is observed until their complete disappearance. Vacuolization of mitochondria of motor nerve terminals is also noted.

Action β- bungarotoxin is similar to the action of botulinum toxin, which also affects the mechanism for the release of acetylcholine from nerve endings. However, there are differences: botulinum toxin does not cause an initial increase in PEP; unlike botulism toxin β- bungarotoxin interacts only with cholinergic endings; No changes in the presynaptic area were observed under the action of botulinum toxin.

The ability was revealed on synaptosomes from the rat brain β- bungarotoxin reduces the accumulation of GABA, serotonin, norepinephrine and choline. Since β- Bungarotoxin mainly displaces already accumulated neurotransmitters; it can be assumed that its action is associated with damage to the storage process, and not the transport of mediators.

Conclusion

The mechanism of action of snake venoms has not yet been fully deciphered by scientists. But a transparent drop of poison, once in the blood, spreads throughout the body and, in a certain dose, has a beneficial effect on the patient’s body. It has been established that small amounts of cobra venom have an analgesic effect and can even be used as a morphine substitute in patients suffering from malignant neoplasms. Moreover, unlike morphine, snake venom acts longer and, most importantly, is not addictive. In addition, drugs based on cobra venom have been created that improve the general condition of patients suffering from bronchial asthma, epilepsy, and angina pectoris.

The need for snake venom is increasing from year to year, and snake nurseries established in a number of regions of our country cannot yet satisfy this need. Therefore, there is a need to protect venomous snakes in natural conditions, as well as to ensure their reproduction in captivity.

It should be remembered that in the hands of inexperienced people, snake venom becomes not an ally in the fight to maintain health, but a dangerous enemy and can cause severe poisoning. Theophrastus Paracelsus spoke about the need to correctly select the dose of a medicinal substance, arguing that “...everything is poison, nothing is devoid of poisonousness, and everything is medicine. The dose alone makes a substance a poison or a medicine.” This saying of the famous scientist has not lost its meaning even today, and when using snake venoms, patients are obliged to strictly follow the instructions of the attending physician.

Snake venoms are known to be dangerous to many species of mammals. But among lower organized animals, especially among insects, species are known that are not susceptible to the action of snake venom, which allows them to be used as antidotes.

Summing up the consideration of a range of issues covering the features of the chemical structure and mechanisms of action of poisons, it is impossible not to mention that Nature - this most skillful experimenter - has given researchers unique tools for studying fundamental issues of the structure and functioning of a living cell.

Zootoxins are excellent models for molecular biology, allowing one to address questions of structure-function relationships in biomolecules.

References

1. Orlov B.N. “Poisonous animals and plants of the USSR.” M.: Higher School, 1990. - 272 s.

G.I. Oxendendler “Poisons and Antidotes” L.: Nauka, 1982. - 192 p.

E. Dunaev, I. Kaurov “Reptiles. Amphibians." M.: Astrel, 2010. - 180s.

B.S. Tuniev, N.L. Orlov "Snakes of the Caucasus". M.: Partnership of scientific publications KMK, 2009. - 223 p.

www.floranimal.ru

http://www.ncbi.nlm.nih.gov/pubmed