Finding into the body of alien substances. Immunology for teapots

Under the term "immunity" (from lat. Immunitas - the deliverance from anything) implies the immunity of the body to infectious and noncommunicable agents. Animal and people's organisms very clearly differentiate "their" and "alien", due to which protection is ensured not only from the introduction of pathogenic microorganisms, but also from alien proteins, polysaccharides, lipopolysaccharides and other substances.

The protective factors of the body against infectious agents and other alien substances are divided into:

- nonspecific resistance - Mechanical, physicochemical, cellular, humoral, physiological protective reactions aimed at preserving the constancy of the internal environment and restore the disturbed functions of the macroorganism.

- congenital immunity - The resistance of the body to certain pathogen agents, which is inherited and inherent in a certain type.

- Acquired immunity - Specific protection against genetically alien substances (antigens), carried out by an immune system of the body as an antibody generation.

Nonspecific resistance of the body is due to such protection factors that do not need special restructuring, but they neutralize alien bodies and substances mainly due to mechanical or physicochemical influences. These include:

The skin is a physical obstacle on the path of microorganisms, it simultaneously has a bactericidal property against the causative agents of gastrointestinal and other diseases. The bactericidal effect of the skin depends on its purity. On contaminated skin, the microbes are saved longer than on clean.

The mucous membranes of the eyes, nose, mouth, stomach and other organs, like skin barriers, as a result of impermeability of them for various microbes and bactericidal action of secrets, antimicrobial functions are carried out. In a tear liquid, sputum, saliva is a specific lysozyme protein, which causes "lysis" (dissolution) of many microbes.

Gastric juice (its composition includes hydrochloric acid) has very pronounced bactericidal properties against many pathogens, especially intestinal infections.

Lymph nodes - pathogenic microbes are delayed and neutralized. In lymph nodes, inflammation is developing, which is deducting on causative agents of infectious diseases.

Phagocytic reaction (phagocytosis) - opened it I.I. Swords. He proved that some blood cells (leukocytes) are able to capture and digest the microbes, freeing the organism from them. Such cells are called phagocytes.

Antibodies - special specific substances of microbial nature, capable of inactivating the microbes and their toxins. These protective substances in various tissues and organs (spleen, lymph nodes, bone marrow). They are produced in the introduction of pathogenic microbes, alien protein substances, serums of other animals in the body, etc. All substances that can cause the formation of antibodies - antigens.

Acquired immunity can be natural, appearing as a result of the suffered infectious disease and artificial, which is acquired due to the introduction of specific biological preparations into the body - vaccines and sera.

Vaccines are killed or weakened causative agents of infectious diseases or their neutralized toxins. Acquired immunity is active, i.e. Arriving as a result of the active struggle of the body with the causative agent of the disease.

Alien Chemicals (ChV) They are called xenobiotics (from Greek. XeNOs - someone else's). They include compounds that are not inherent in their nature and the number of natural product, but can be added to improve the technology, maintaining or improving the quality of the product, or they may form in the product as a result of technological processing and storage, as well as in contact with the surrounding medium. From the environment in the human body with food, 30-80% of the total number of alien chemicals are coming.

Alien substances can be classified by the nature of the action, toxicity and the degree of danger.

Broaktera action ChV, entering the body with food, can:

· Property generaloxic act;

· Property Allergic action (sensitizing the body);

· Property Carcinogenic action (cause malignant tumors);

· Property Embryotoxic action (influence on the development of pregnancy and fetus);

· Property Teratogenic action (malformations of the fetus and the birth of offspring with deformities);

· Property Gonadotoxic action (violate the reproductive function, i.e. violate the reproduction function);

· Reduce protective forces organism;

· Accelerate processes of aging;

· Adversely influence digestion and assimilation foodstuffs.

Flowstone, Characterizing the ability of the substance to cause harm to the body, take into account the dose, frequency, method of receipt of a harmful substance and the picture of poisoning.

By degree of danger Alien substances are divided into extremely toxic, highly toxic, moderateotoxic, small-toxic, practically non-toxic and practically harmless.

The most studied acute effects of harmful substances that have direct action. It is especially difficult to assess the chronic effect of the Chief on the human body and their long-term consequences.

Harmful effect on the body can provide:

· Products containing nutritional supplements (dyes, preservatives, antioxidants, etc.) - non-executive, unresolved or used in elevated doses;

· Products or individual foodstuffs obtained by new technology, by chemical or microbiological synthesis, not tested or manufactured with impaired technology or non-fixed raw materials;

· Residual amounts of pesticides contained in crop production products or animal husbandry obtained using feed or water contaminated with high pesticide concentrations or due to the treatment of animal pesticides;

· Crop products obtained using non-executed, unresolved or infrequently used fertilizers and irrigation waters (mineral fertilizers and other agrochemicals, solid and liquid waste industry and livestock production, household waste water, precipitation from sewage treatment facilities, etc.);

· Products of animal husbandry and poultry farming, obtained using unappointed, unresolved or incorrectly applied feed additives and preservatives (mineral and nitrogenous additives, growth stimulants - antibiotics, hormonal preparations, etc.). This group includes contamination of products related to veterinary and prophylactic and therapeutic measures (antibiotics, antiflammation and other medicines);

· Toxicants who migrated to products from equipment, dishes, inventory, containers, packages when using non-tested or unresolved plastics, polymer, rubber or other materials;

· Toxic substances formed in food products during heat treatment, smoke, roasting, enzyme treatment, irradiation with ionizing radiation, etc.;

· Food products containing toxic substances migrating from the environment: atmospheric air, soil, water bodies (heavy metals, dioxins, polycyclic aromatic hydrocarbons, radionuclides, etc.). This group includes the greatest number of CHW.

One of the possible ways of receipt of the Chief of the Environment in food is the inclusion of them in the "food chain".

"Food chains"they are one of the basic forms of relationship between individual organisms, each of which serves as food for other species. In this case, there is a continuous series of conversion of substances in consecutive links "victim-predator". The main options for such chains are presented in Fig. 2. The chains in which pollutants come from the soil to plant products (mushrooms, greens, vegetables, fruits, grain crops) as a result of watering plants, treatment of pesticides, etc., accumulate in them, and then come to food human organism.

More complex are "chains" under which there are several units. For instance, grass - herbivores - man or grain - Birds and Animals - Man. The most complex "food chains" is usually associated with the water medium.

Fig. 2. Options for the arrival of the chief in the human body through food chains

The substances dissolved in water are extracted with phytoplastic, the latter is then absorbed by zooplankton (the simplest, races), then absorbs "peaceful" and then predatory fish, acting with them into the human body. But the chain can be continued by eating fish by birds and omnivorous animals and only then harmful substances enter the human body.

A feature of the "food chains" is that in each subsequent link it occurs a cumulation (accumulation) of pollutants in much larger quantities than in the previous link. So, in the mushrooms, the concentration of radioactive substances can be 1,000-10,000 times higher than in the soil. Thus, in food products entering the human body, there may be very large concentrations of ChV.

In order to protect human health from the harmful effects of alien substances entering the body with food, certain limits are established, guaranteeing the safety of the use of products in which foreign substances are present.

The basic principles of environmental protection and food products from foreign chemicals include:

· Hygienic rationing of the content of chemicals in environmental facilities (air, water, soil, food products) and development based on sanitary legislation (sanitary rules, etc.);

· Development of new technologies in various industries and agriculture, minimally polluting the environment (replacement of particularly hazardous chemicals less toxic and unstable in the environment; sealing and automation of production processes; transition to waste-free production, closed cycles, etc.);

· Implementation in enterprises of effective sanitary and technical devices to reduce emissions of harmful substances into the atmosphere, wastewater disposal, solid waste, etc.;

· Development and implementation in the construction of planned activities warning environmental pollution (selection site for the construction of an object, creating a zone of sanitary protection, etc.);

· Implementation of state sanitary and epidemiological oversight of objects polluting atmospheric air, reservoirs, soil, food raw materials;

· Implementation of state sanitary and epidemiological surveillance of objects where pollution of food raw materials and food products CHF (food industry enterprises, agricultural enterprises, food warehouses, catering enterprises, etc.) can occur.

In food

Alien chemical substances are connected to the compounds that are not inherent in their nature and the number of natural product, but can be added to improve the technology of preserving or improving the quality of the product and its food properties, or they can form in the product as a result of technological processing (heating, fry, irradiations, etc.) and storage, as well as get into it or in food due to pollution.

According to foreign researchers, out of the total number of foreign chemicals penetrating the environment in the human body, depending on the local conditions, 30-80% and more comes with food (K. Noran, 1976).

The spectrum of the possible pathogenic effect of the Chief entering the body with food is very wide. They can:

1) adversely affect the digestion and absorption of food substances;

2) lower the protective forces of the body;

3) sensitizing the body;

4) provide a general-toxic effect;

5) cause gonadotoxic, embryotoxic, teratogenic and carcinogenic effects;

6) accelerate aging processes;

7) violate the reproduction function.

The problem of the negative impact of environmental pollution on human health is becoming more acute. She turned out the national borders and became global. Intensive industry development, chemicals of agriculture lead to the fact that in the environment, chemical compounds, harmful to the human body appear in large quantities. It is known that a significant part of alien substances enters the human body with food (for example, heavy metals - up to 70%). Therefore, wide information of the population and specialists about pollutants in food has a great practical value. The presence in food products of pollutants that do not have food and biological value or toxic, threatens human health. Naturally, this problem relating to both traditional and new food has become particularly acute. The concept of "alien substance" became the center around which the discussions still flared up. The World Health Organization and other international organizations have been hardly engaged in these issues for about 40 years, and the health authorities are trying to control them and implement food certification. Pollutants may fall into food in the form of contaminants in the form of contaminants, and sometimes they are injected specifically in the form of food additives when it is supposedly related to the technological necessity. In food, pollutants can under certain conditions cause food intoxication, which is a danger to human health. At the same time, the general toxicological situation is further complicated by the frequent admission of other non-food products, substances, such as drugs; Finding into the body of alien substances in the form of by-products of manufacturing and other types of human activity through air, water, consumed products and medicines. Chemicals that fall into food from the environment surrounding us create problems whose solution is an urgent need. As a result, it is necessary to assess the biological importance of the threat of these substances to human health and disclose its connection with pathological phenomena in the human body.

One of the possible ways of receipt of the chief in food is the inclusion of them in the so-called food chain.

Thus, in the food entering the human body, there may be very large concentrations of substances that have called alien substances (chv).

Food chains are one of the main forms of the relationship between different organisms, each of which deviates another species, in this case there is a continuous series of transformations of substances in consecutive links of the victim - a predator. The main versions of such food chains are shown in the figure. The most simple chains in which in vegetable products are: mushrooms, spicy plants (parsley, dill, celery, etc.), vegetables and fruits, grain crops - flow pollutants from the soil as a result of watering plants (from water), processing of plants with pesticides to combat pests; They are recorded and in some cases accumulated in them and then together with food enter the human body, acquiring the opportunity to have a positive or, more often, adverse effects.

More complex are chains at which there are several links. For example, grass - herbivores - a man or grain - birds and animals - a man. The most complex food chains are usually associated with the water medium. The substances dissolved in water are extracted by phytoplankton, the latter is then absorbed by zooplankton (the simplest, races), then absorbs "peaceful" and then predatory fish, acting with them after that in the human body. But the chain can be continued by eating fish by birds and omnivorous animals (pigs, bears) and only then - the admission to the human body. A feature of the food chains is that in each subsequent linking, there is a cumulation (accumulation) of pollutants in much larger quantities than in the previous link. Thus, according to V. Eichler, in relation to drugs DDT algae, when extracting from water, can increase (accumulate) the concentration of the drug 3000 times; In the body of crustaceans, this concentration increases another 30 times; in the body of the fish - another 10-15 times; And in the adipose tissue of chaps that eat this fish - 400 times. Of course, the degree of accumulation of certain pollution in the units of the food chain may differ very much depending on the type of contamination and the nature of the chain link. It is known, for example, that in the mushrooms the concentration of radioactive substances can be 1000-10,000 times higher than in the soil.

Options for foreign substances

Penetrating the body of the poisons, like other alien compounds, may be subjected to a variety of biochemical transformations ( biotransformation), as a result of which less toxic substances are most often formed ( neutrality, or detoxification). But there are many cases of amplification of poison toxicity when changing their structure in the body. There are also such compounds whose characteristic properties begin to manifest itself only as a result of biotransformation. At the same time, a certain part of the poison molecules is distinguished from the body without any changes or it remains in it to a more or less long period, fixing blood plasma and tissue proteins. Depending on the strength of the formed complex "poison protein", the effect of poison slows down or is lost at all. In addition, the protein structure can only be a carrier of a poisonous substance delivering it to the appropriate receptors. *

* ( The term "receptor" (or "receptor structure") will be denoted by the "point of the application" poisons: an enzyme, an object of its catalytic effect (substrate), as well as protein, lipid, mucopolysaccharide and other bodies that constitute the structure of cells or participating in metabolism. Molecular pharmacological ideas about the essence of these concepts will be discussed in ch. 2.)

The study of biotransformation processes allows to solve a number of practical issues of toxicology. First, the knowledge of the molecular essence of the detoxification of poisons makes it possible to hide the body's protective mechanisms and on this basis, outline ways of directional impact on the toxic process. Secondly, the value of the dose of poison (drugs) of the dose of poison (drugs) can be judged by the number of ways over the kidneys, intestines and light products of their transformation - metabolites, * what makes it possible to control the health of people engaged in the production and use of toxic substances; In addition, with various diseases, the formation and allocation of alien substances from the body of many products of the biotransformation is significantly violated. Thirdly, the appearance of poisons in the body is often accompanied by induction of enzymes catalyzing (accelerating) transform them. Therefore, affecting the help of certain substances on the activity of induced enzymes, one can accelerate or brake the biochemical processes of transformations of alien compounds.

* ( Under the metabolites, it is also accepted to understand the various biochemical products of normal metabolism (metabolism))

Currently it has been established that the processes of biotransformation of alien substances flow in the liver, gastrointestinal tract, lungs, kidneys (Fig. 1). In addition, according to the results of the studies of Professor I. D. Gadskina, * a considerable number of toxic compounds is exposed to irreversible transformations and in adipose tissue. However, the main importance here has a liver, more precisely - the microsomal fraction of its cells. It is in liver cells, in their endoplasmic reticulum, the majority of enzymes catalyzing the conversion of alien substances are localized. The reticulum itself is a plexusion of lennopoid tubes, penetrating the cytoplasm (Fig. 2). The highest enzymatic activity is associated with the so-called smooth reticulum, which, unlike the rough, does not have ribosomes on its surface. ** It is not surprising that, in diseases of the liver, the sensitivity of the body to many alien substances is sharply increasing. It should be noted that, although the number of microsomal enzymes is small, they have a very important property - high affinity for various alien substances with relative chemical nonspecificness. This creates them to enter into a reaction of neutralization with almost any chemical compound that fell into the inner media. Recently, the presence of a number of such enzymes in other organides of the cell (for example, in mitochondria), as well as in plasma and in the intestinal microorganisms) has been proved.

* ( Gadascina I. D. Fatty fabric and poisons. - In the book: Actual issues of industrial toxicology / Ed. N. V. Lazareva, A. A. Golubev, E. T. Lohipoy. L., 1970, p. 21-43)

** ( Ribosomes - spherical cell formations with a diameter of 15-30 nm, which are centers of protein synthesis, including enzymes; contain ribonucleic acid (RNA))

It is believed that the main principle of transformation in the body of alien compounds is to ensure the greatest speed of their elimination by transferring from fat-soluble in more water-soluble chemical structures. In the last 10-15 years, when studying the essence of biochemical transformations of alien compounds from fat-soluble in water-soluble increasing importance is attached to the so-called monooxygenase enzyme system with a mixed function, which contains a special protein - cytochrome P-450. It is close in structure to hemoglobin (in particular, it contains iron atoms with valence variable) and is a finite link in the group of oxidizing microsomal enzymes - biotransformers focused mainly in liver cells. * In the body cytochrome P-450 may be in 2 forms: oxidized and restored. In the oxidized state, it first forms a comprehensive compound with a foreign substance, which after that is restored by a special enzyme - cytochromeductase. Then this, already restored, the compound reacts with activated oxygen, resulting in an oxidized and, as a rule, a non-toxic substance.

* ( Kovalev I. E., Malenkov A. G. Flow of alien substances: influence on humanity - Nature, 1980, No. 9, p. 90-101)

Based on biotransformation of toxic substances lies several types of chemical reactions, as a result of which there is an attachment or the cleavage of metallic (-CH 3), acetyl (CH 3 co-), carboxyl (-son), hydroxyl (-on) radicals (groups), as well as sulfur atoms and sulfur-containing groupings. The processes of decay of molecules of poisons are considerable significance to the irreversible transformation of their cyclic radicals. But a special role among poisons disposal mechanisms play synthesis reactions, or conjugationAs a result of which non-toxic complexes are formed - conjugates. In this case, the biochemical components of the inner medium of the body, entering into irreversible interaction with poisons, are: glucuronic acid (C 5 H 9 O 5 7), cysteine \u200b\u200b( ), glycine (NH 2 -ch 2 -COH), sulfuric acid, etc. Poons molecules containing several functional groups can be transformed by 2 or more metabolic reactions. Along the way, we note one substantive circumstance: since the transformation and detoxification of poisonous substances due to the conjugation reactions are associated with the expenditure of substances important for life, then these processes can cause the latter in the body. Thus, the danger of another kind of other kind is the possibility of the development of secondary painful states due to the lack of the necessary metabolites. Thus, the detoxification of many alien substances is depending on the glycogen reserves in the liver, since glucuronic acid is formed from it. Therefore, when entering large doses of substances into the body, the neutralization of which is carried out by the formation of glucuronic acid esters (for example, benzene derivatives), the content of glycogen is reduced - the main easily mobilized reserve of carbohydrates. On the other hand, there are substances that under the influence of enzymes are able to eliminate glucuronic acid molecules and thereby contribute to the neutralization of poisons. One of these substances was glycyrrizine, which is part of the licorice root. Glycyrrrizin contains 2 glucuronic acid molecules in the associated state, which are exempted in the body, and this seems to determine the protective properties of the licorice root with many poisoning, which have long been long-looking medicine, Tibet, Japan. *

* ( Salo V. M. Plants and Medicine. M.: Science, 1968)

As for the removal of toxic substances and the products of their transformation from the body, the light, digestive, leather, various glands play a certain role in this process. But there are the greatest importance in the night. That is why with many poisoning with the help of special means that enhances the separation of urine, achieve the fastest removal of poisonous compounds from the body. At the same time, it is necessary to reckon with the damaging effect on the kidneys of some of the poisons derived from the urine (for example, mercury). In addition, the conversion of toxic substances can be delayed in the kidneys, as is the case with severe ethylene glycol poisoning. * With its oxidation in the body, oxalic acid is formed and the calcium oxalate crystals are falling out in the renal tubules, which prevent urinations. In general, such phenomena are observed when the concentration of the substances derived through the kidneys are high.

* ( Ethylene glycol is used as antifreeze - substance that reduces the freezing temperature of combustible liquids in internal combustion engines)

In order to understand the biochemical essence of the transformation processes in the body of poisonous substances, consider several examples relating to the common components of the chemical environment of a modern person.

So, benzene, which, similar to other aromatic hydrocarbons, is widely used as a solvent of various substances and as an intermediate product in the synthesis of dyes, plastic masses, drugs and other compounds, is transformed in the body in 3 directions to form toxic metabolites (Fig. 3). The latter stand out through the kidneys. Benzole may very long (according to some data, up to 10 years) linger in the body, especially in adipose tissue.

Certain interest is the study of the transformation processes in the body toxic metalsproviding an increasing impact on a person in connection with the development of science and technology and the development of natural wealth. First of all, it should be noted that as a result of the interaction with oxidative-reducing buffer systems, the cells in which the electron transfer is carried out, the valence of metals changes. In this case, the transition to a state of low valence is usually associated with a decrease in the toxicity of metals. For example, the hexavalent chromium ions go in the body into a small-toxic trivalent shape, and the trivalent chrome succeeds in rather quickly removed from the body using some substances (sodium pyrosulfate, wine-names, etc.). A number of metals (mercury, cadmium, copper, nickel) are actively associated with biocomplexes, first of all, with functional groups of enzymes (-sh, -nh 2, -son, etc.), which sometimes determines the selectivity of their biological action.

Among yadohimikatov - substances designed to destroy harmful living beings and plants, there are representatives of various classes of chemical compounds, in one way or another toxic for humans: chlororganic, phosphorod, organometallic, nitrophenolic, cyanide, etc. According to available data, * about 10% of all deaths Poisoning is currently caused by pesticides. The most significant of them, as you know, are FOS. Hydrolyzing, they, as a rule, lose toxicity. In contrast to hydrolysis, the oxidation of the FOS is almost always accompanied by the enhancement of their toxicity. This can be seen if you compare the biotransformation of 2 insecticides - diisopropylfluorphosphate, which loses the toxic properties, cleaves the fluorine atom, and thiophos (derivative of thiothosphoric acid), which is oxidized to a significantly more toxic phospoli (orthophosphoric acid derivative).

* ( Buslovich S. Yu., Zakharov G. G. Clinic and the treatment of acute poisoning by pesticides (pesticides). Minsk: Belarus, 1972)

Among widely used medicinal substances Sad preparations are the most frequent sources of poisoning. The processes of their transformations in the body are well understood quite well. In particular, it is shown that the biotransformation of one of the common derivatives of barbituric acid - luminal (Fig. 4) - flows slowly, and this underlies its sufficiently long-term sleeping action, as it depends on the number of unchanged luminal molecules in contact with nerve cells. The decay of the barbituro ring leads to the termination of the eliminal action (as, however, and other barbiturates), which in therapeutic doses causes a duration of up to 6 hours. In this regard, the fate in the body of another representative of Barbiturates - hexobarbital is not expensive. His hypnotic action is much shorter even when applying significantly large than luminal, doses. It is believed that it depends on greater speed and from a larger number of ways to inactivating the hexobarbital in the body (the formation of alcohols, ketones, demethylated and other derivatives). On the other hand, those barbiturates that persist in the body are almost unchanged, such as barbitital, have a longer sleeping reaction, than luminal. It follows from this that substances that are unchanged with urine can cause intoxication if the kidneys do not cope with their removal from the body.

It is also important to note that in order to understand the unforeseen toxic effect, with the simultaneous use of several drugs, proper importance should be given to enzymes affecting the activity of combining substances. Thus, for example, a physostymin's drug with novocaine with novocaine makes the latter with a very toxic substance, since the enzyme blocks (Esterase), hydrolyzing novocaine in the body. Ephedrine also shows itself, associating oxidase, inactivating adrenaline and thereby extending and strengthening the effect of the latter.

The processes of induction (activation) and braking of the activity of microscale enzymes of different alien substances play a major role in biotransformation of drugs. So, ethyl alcohol, some insecticides, nicotine accelerate the inactivation of many drugs. Therefore, pharmacologists pay attention to the unwanted consequences of contact with these substances against the background of drug therapy, in which the therapeutic effect of a number of drugs decreases. B The same time should be borne in mind that if contact with the inducer of microsomal enzymes suddenly stops, then this can lead to a toxic effect of drugs and will require a decrease in their doses.

It must also be borne in mind that, according to the World Health Organization (WHO), in 2.5% of the population significantly increased the risk of drug toxicity, since the genetically determined period of their half-life in the blood plasma in this group of people is 3 times more average. At the same time, about a third of all enzymes described in the person in many ethnic groups are represented by various activity by their activity. Hence the individual differences in the reactions of a PA one or another pharmacological agent, depending on the interaction of many genetic factors. So, it was established that approximately one by one by 1-2 thousand people sharply reduced the activity of a serum cholinesterase, which hydrolyzens dithiline - means used to relax skeletal muscles for several minutes with some surgical interventions. In such people, dithiline is dramatically lengthened (up to 2 hours or more) and can become a source of severe state.

Among people living in the countries of the Mediterranean, in Africa and Southeast Asia, there is a genetically determined insufficient activity of the enzyme enzyme glucose-6-phosphate-dehydrogenase of red blood cells (a decrease of up to 20% of the norm). This feature makes red blood cells to a number of medicines: sulfonamides, some antibiotics, a fenacetine. Due to the collapse of red blood cells, hemolytic anemia and jaundice arise in such persons against the background of drug treatment. It is clear that the prevention of these complications should be to preliminarily determine the activity of the respective enzymes in patients.

Although the above material only provides an idea of \u200b\u200bthe problem of biotransformation of toxic substances, it shows that the human body has many protective biochemical mechanisms, which to a certain extent protect it from the unwanted effects of these substances, at least from small doses. The functioning of such a complex barrier system is provided by numerous enzyme cultures, the active impact on which makes it possible to change the flow of transformation and neutralization of poisons. But this is one of the next topics. With further presentation, we will still return to the consideration of certain aspects of the conversion of some toxic substances to the body to the extent necessary to understand the molecular mechanisms of their biological action.

The multifaceted food impact on the human body is due not only to the presence of energy and plastic materials, but also a huge amount of food, including minor components, as well as unawartieuction compounds. The latter may have pharmacological activity or to have an adverse effect.

The concept of biotransformation of alien substances includes on the one hand, the processes of their transport, metabolism and toxicity implementations, on the other hand, the possibility of the influence of individual nutrients and their complexes to these systems, which ultimately ensures neutralization and elimination of xenobiotics. At the same time, some of them have high resistance to biotransformation and damage to health. In this aspect, it should also be noted the term detoxification - The process of neutralizing inside the biological system of harmful substances in it. Currently, a fairly large scientific material has been gained on the existence of general mechanisms for toxicity and biotransformation of alien substances, taking into account their chemical nature and the condition of the body. The most studied the mechanism of two-phase detoxification of xenobiotics.

At the first stage, their metabolic transformations in various intermediate connections occur as a response of the organism. This stage is associated with the implementation of enzymatic oxidation reactions, restoration and hydrolysis, which occur, as a rule, in vitality and tissues: liver, kidneys, lungs, blood, etc.

Oxidation Xenobiotics catalyze microsomal liver enzymes with the participation of cytochrome P-450. The enzyme has a large number of specific isoforms, which explains the diversity of toxicants subjected to oxidation.

Restoration It is carried out with the participation of postpon-dependent flavoproteide and cytochrome P-450. As an example, the reaction of the restoration of nitro and azo compounds in the amines, ketones in secondary alcohols can be obtained.

Hydrolytic decay Understand, as a rule, esters and amides followed by deterification and deification.

The above paths of biotransformation lead to changes in the xenobiotic molecule - the polarity, solubility, etc. is increasing. This contributes to their removal from the body, decrease or disappear to the toxic effect.

However, primary metabolites may have a high reactivity and greater toxicity compared to the initial toxic substances. Such a phenomenon was called metabolic activation. Reactive metabolites reach target cells, launch a chain of secondary catobiochemical processes underlying the mechanism of hepatotoxic, nephrotoxic, carcinogenic, mutagenic, immunogenic actions and related diseases.

Of particular importance in the consideration of the toxicity of xenobiotics is the formation of free radical intermediate oxidation products, which, along with the products of reactive oxygen metabolites, leads to the induction of the lipid peroxidation (floor) of biological membranes and the damage to the living cell. In this case, an important role is given to the state of the antioxidant system of the body.

The second phase of detoxification is associated with the so-called reactions conjugation. An example of the binding reactions of active -one; -NH 2; -Son; SH-groups of xenobiotic metabolites. The most active participation in the reactions of neutralization is taken by the enzymes of the glutathiontransferase family, glucoronyltransferase, sulfotransferase, acyltransferase, etc.

In fig. 6 shows the general scheme of metabolism and the mechanism of toxicity of alien substances.

Fig. 6.

The metabolism of xenobiotics can influence many factors: genetic, physiological, environmental factors, etc.

Represents theoretical and practical interest to dwell on the role of individual components of food in the regulation of metabolic processes and the implementation of the toxicity of alien substances. Such participation can be carried out at the suction stages in the gastrointestinal tract, hepatic circulation, blood transport, localization in tissues and cells.

Among the main mechanisms of biotransformation of xenobiotics, the processes of conjugation with reduced glutathyone - T-U-glutamyl-b-cycinyl glycine (TSH) are important - the main thiol component of most living cells. TSH has the ability to restore hydropercy in the glutathioneperoxide reaction, is a cofactor as part of formaldehyde-hydrogenase and glyoxylase. Its concentration in the cell (cellular pool) is substantially depends on the content in the diet of protein and sulfur-containing amino acids (cysteine \u200b\u200band methionine), therefore the deficiency of these nutrients increases the toxicity of a wide range of hazardous chemicals.

As noted above, an important role in the preservation of the structure and functions of the living cell, when exposed to active oxygen metabolites and free radical products of alien oxidation products, is given to the antioxidant system of the body. It consists of the following main components: superoxidismutase (soda), reduced glutathione, some forms of glutathione-b-transferase, vitamins E, C, R-carotene, selenium microelement - as a cofactor of glutathioneer peroxidase, as well as nonialimentary food components - a wide range of phyto compounds (bioflavonoids ).

Each of these compounds has specificity of action in a common metabolic conveyor that form an antioxidant body protection system:

• SOD, in two of its forms - cytoplasmic CU-Zn-soda and mitochondrial-MP-dependent, catalyzes the dismutation reaction 0 2 _ into hydrogen peroxide and cosnag;
• ESH (taking into account its above functions) implements its action in several directions: Supports sulfhydryl groups of proteins in a reduced state, serves as a proton donor for glutathioneer peroxidase and glutathione-b-transferase, acts as a non-specific nonferred amount of oxygen radicals, develops ultimately , in oxidative glutathione (TSSR). Its reduction is catalyzed by the soluble PDFN-dependent glutathioneducetase, which is vitamin B 2, which determines the role of the latter in one of the ways of biotransformation of xenobiotics.

Vitamin E (OS-tocopherol). The most significant role in the regulation system floor belongs vitamin E, which neutralizes free radicals of fatty acids and reduced oxygen metabolites. The protector role of tocopherol is shown in the effects of a variety of pollutants of the environment induced by the floor: ozone, N0 2, CC1 4, CD, PB, etc.

Along with the antioxidant activity, vitamin E has anticarceregenic properties - inhibits in the gastrointestinal tract N-nitrosation of secondary and tertiary amines with the formation of carcinogenic N-nitrosamines, has the ability to block xenobiotics mutaging, has an impact on the activity of the monooxygenase system.

Vitamin C. Antioxidant action of ascorbic acid under the conditions of the effects of toxic substances induced by the floor, exhibits in an increase in the level of cytochrome P-450, the activity of its reductase and the hydroxylation rate of substrates in the liver microscoms.

The most important properties of vitamin C associated with the metabolism of alien compounds are also:

• the ability to inhibit covalent binding to macromolecules of active intermediate compounds of various xenobiotics - acetomyonophos, benzene, phenol, etc.;
• Block (similar to vitamin E) nitrosation of amines and the formation of carcinogenic compounds under conditions of impact of nitrite.

Many alien substances, such as tobacco smoke components, oxidize ascorbic acid to dehydroaskorbat, thereby reducing its content in the body. This mechanism is based on the determination of vitamin security with smokers, organized teams, including workers industrial enterprises in contact with harmful alien substances.

For the prevention of chemical carcinogenesis, the Laureate of the Nobel Prize L. Pauling recommended the use of megadosis exceeding the daily need of 10 or more times. The feasibility and effectiveness of such quantities remain controversial, since the saturation of the tissues of the human body under these conditions is provided by daily consumption of 200 mg of ascorbic acid.

Unalimental components of food forming an antioxidant system of the body include food fibers and biologically active phyto compounds.

Alimentary fiber. These include cellulose, hemicellulose, pectins and lignin, which have vegetable origins and are not exposed to digestive enzymes.

Food fibers can influence the biotransformation of alien substances in the following directions:

• affecting the rebagging of the intestines, accelerate the passage of content and reduce the time of contact of the toxic substances with the mucous membrane;
• The composition of the microflora and the activity of microbial enzymes involved in the metabolism of xenobiotics or their conjugates are changed;
• They have adsorption and cation exchange properties, which makes it possible to bind chemical agents, delay their suction and accelerate the elimination of the body. These properties also have an impact on the liver-intestinal circulation and provide the metabolism of xenobiotics entering the body in various ways.

Experimental and clinical studies found that the inclusion of cellulose, carragein, guarantine resins, pectin, wheat bran, leads to inhibition (3-glucoronidases and muds of intestinal microorganisms. Such an effect should be considered as another ability of food fibers to transform alien substances by obstacle to the hydrolysis of conjugates These substances, removal of them from the hepatic circulation and enhancing excretion from the body with the exchange products.

There are data on the ability of low-substituted pectin to bind mercury, cobalt, lead, nickel, cadmium, manganese and strontium. However, such an ability of individual pectins depends on their origin, requires studying and electoral application. For example, the citrus pectin does not show visible adsorption effect, it is weakly activated (3-glucoronidase intestinal microflora is characterized by the absence of prophylactic properties in the chemical carcinogenesis induced.

Biologically active fito compounds. Neutralization of toxic substances involving phyto compounds is associated with their main properties:

• affect the processes of metabolism and neutralize alien substances;
• have the ability to associate free radicals and reaction-capable metabolites of xenobiotics;
• Inhibit enzymes that activate alien substances and activate the detoxification enzymes.

Many of natural phyto compounds have specific properties of inductors or inhibitors of toxic agents. The organic compounds contained in the zucchini, color and Brussels cabbage, broccoli, are capable of inducing the metabolism of alien substances, which is confirmed by the acceleration of the exchange of phenacetin, the acceleration of the half-life of the antipyrin in the blood plasma of the tests received with the diet of the cross-tech family.

Special attention is paid to the properties of these compounds, as well as the phyto compounds of tea and coffee - catechins and diterpenes (kaffa and cafestes) to stimulate the activity of the monooxygenase system and glutathione-S-transferase of the liver and the intestinal mucosa. The latter underlies their antioxidant effect when exposed to carcinogens and anticancer activity.

It is advisable to dwell on the biological role of other vitamins in the processes of biotransformation of alien substances that are not associated with an antioxidant system.

Many vitamins perform the functions of coherers directly in enzyme systems associated with the exchange of xenobiotics, as well as in the biosynthesis enzymes of components of biotransformation systems.

Tiamine (vitamin B T). It is known that the insufficiency of thiamine is the cause of increasing the activity and content of the components of the monooxygenase system, which is considered as an unfavorable factor contributing to the metabolic activation of alien substances. Therefore, the security of vitamins can play a role in the detoxification mechanism of xenobiotics, including industrial poisons.

Riboflavin (Vitamin B 2). The functions of riboflavin in the processes of biotransformation of alien substances are implemented mainly through the following metabolic processes:

• Participation in the metabolism of microsomal flavoproteins APFN-cytochter R-450 reductase, NAPFN-cytochrome-b 5 - reductase;
• Ensuring the operation of aldehydoxidases, as well as glutationeer-duktase through the coenses of the FAD with the implementation of TSH generation from oxidized glutathione.

In the experiment on animals, it was shown that the deficiency of vitamin leads to a decrease in the activity of UDF-glucoronyltransferase in the liver microsomes based on the indicator of the reduction in the speed of glucuronide conjugation / 7-nitrophenol and o-aminophenol. There are data on increasing the content of cytochrome P-450 and the hydroxylation velocity of ammopypyrin and aniline in microscoms during the alimentary insufficiency of riboflav in mice.

Cobalamins (vitamin B 12) and folic acid. The synergistic effect of the vitamins under consideration on the processes of biotransformation of xenobiotics is explained by the lipotropic effect of the complex of these nutrients, the most important element of which is the activation of glutathione-b-transferase and organic induction of the monoxygenic system.

When carrying out clinical trials, the development of vitamin C 12 is shown when exposed to nitrogen overhangs, which is explained by the oxidation of C0 2+ in with E + Corrin Ring of the Koba Lamine and its inactivation. The latter causes folic acid deficiency, which is based on the absence of regeneration of its metabolically active forms in these conditions.

Coenager forms of tetrahydrofolytic acid, along with vitamin C 12 and Z-methionine, are involved in formaldehyde oxidation, therefore the deficiency of these vitamins can lead to strengthening formaldehyde toxicity, other single-carbon compounds, including methanol.

In general, it can be concluded that the food factor can play an important role in the processes of biotransformation of alien substances and the prevention of their adverse effects on the body. In this direction, large theoretical material and actual data have been accumulated, but many issues remain open, require further experimental research and clinical confirmations.

It is necessary to emphasize the need for practical ways to implement the preventive role of the factor of nutrition in the methods of metabolism of alien substances. This includes the development of scientifically based diet for individual groups of the population, where there is a risk of impact on the body of various xenobiotics of food and their complexes in the form of biologically active additives, specialized food and diet.