DESINTOXICATION (the fr. des-prefix destruction, removal + intoxication) — a complex of the reactions of an organism directed to reduction biol, activities and concentration of poisons, and also on normalization of the structures and functions broken by them. The main mechanisms D. are neutralization, fixing and acceleration of release of poisons from an organism.
Neutralization (detoxication) is carried out by metabolic transformations of toxic agents as a result of their inclusion in the oxidizing, recovery, hydrolytic and some other reactions catalyzed by the corresponding microsomal and not microsomal fermental systems of an organism. To participation of microsomal enzymes there is an oxidation of toxic agents which belong to acyclic, aromatic and alicyclic compounds, basic nitriles, etc. Microsomal enzymes poisons from group nitro - and azo compounds are exposed to recovery. Hl are exposed to oxidation and recovery under the influence of not microsomal enzymes. obr. alcohols and aldehydes. Hydrolysis of toxic agents (e.g., esters and amides) is carried out with participation of both microsomal, and not microsomal enzymes.
Neutralization of poisons can be carried out also due to conjugation, i.e. by reactions in which poisons connect to endogenous substances (e.g., glucuronic and sulfuric to-tami, amino acids) or to chemical groups (e.g., methyl, acetyl, etc.). Donators of the endogenous substrates necessary for conjugation of poisons, the coenzymes participating in an interstitial metabolism are (uridindifosfatglyukuronovy to - that, atsetil-KOA, glutathione, adenosine coenzymes). Metabolites of toxic agents therefore neutralization of poisons in most cases happens dvukhfazno — in the beginning by metabolic transformations (oxidation, recovery, etc.) are exposed to conjugation most often, and then — by means of conjugation of the formed metabolites. In the course of metabolism and conjugation usually there is a reduction of lyophilic property of toxic agents that facilitates their allocation from an organism.
Fixing of poisons is carried out preferential by their linkng with components of fabrics without change of a chemical structure of toxic agents. At the same time D. results from reduction of concentration of free (untied) poisons in relation to their general concentration in blood and also because in the connected look toxic agents usually are not transported through biol, membranes and therefore do not reach points of application of the action. Distinguish specific and nonspecific fixing of poisons.
Specific fixing of poisons is carried out with participation of immunoglobulins of blood serum and antigen — an antibody proceeds as reactions (see Antigen — an antibody reaction). In such way there is an inactivation of substances (e.g., bacterial toxins, snake and other poisons of animal origin) which have antigenic properties and enter interaction with the corresponding antibodies. A necessary condition of such fixing of poisons is existence in an organism of antibodies, specific in relation to them, that can be reached by preliminary immunization by the corresponding poisons.
Unlike specific, nonspecific fixing of poisons has more universal character. Many can be exposed to process of nonspecific fixing endo-and the exogenous toxic agents belonging to the different classes of chemical connections. At the same time toxic agents communicate hl. obr. with albumine of blood serum. Ions of some metals have the greatest ability to linkng with albumine (e.g., Sa ++ , Mg ++ , Cu ++ , Pb ++ ) and organic matters with anion and cationic properties. Globulins of blood serum in processes of nonspecific fixing of poisons have limited value since only separate substances contact them (e.g., sulfobromftalein, cholesterol, Indo-cyanine green, etc.). Nonspecific fixing of substances blood proteins, as a rule, has reversible character and depends on pH of the environment and extent of ionization of molecules of proteins and poisons. In case of irreversible (covalent) binding of toxic agents (e.g., 2, 4 dinitrobenzene chloride, phenylhydrazine, etc.) with blood proteins the resistant complexes having antigenic properties that can be the cause immunol, a sensitization of an organism to such poisons are formed.
In addition to blood proteins, nonspecific fixing of poisons can be carried out also by other components of fabrics. So, e.g., ions of barium, strontium and lead are fixed in a bone tissue in the form of trifosforny salts or apatites. In fatty tissue hl are fixed. obr. high-lipophilic connections (e.g., DDT, hexachlorobenzene, derivatives thiobarbituric to - you, etc.). At the same time fixing happens by simple distribution of not ionized molecules of such connections in lipids of fatty tissue.
Release of poisons and their metabolites comes from an organism hl. obr. through kidneys, light and excretory glands. Degree and speed of allocation in many respects depend in various ways on physical. - chemical properties of the emitted substances and metabolites. Through kidneys preferential ionized connections which have high hydrophily are allocated and reabsorbirutsya badly in renal tubules (e.g., organic and inorganic to - you, polar sulfates, acetates, conjugates with glucuronic to - that and glycine). Such connections are, as a rule, allocated also with bile. However most actively through a liver high-polar compounds with the molecular weight of 300 and more are allocated. The toxic agents which are emitted with bile in the form of conjugates which are capable to be hydrolyzed under the influence of enzymes of a digestive tract and intestinal microflora can reabsorbirovatsya from it in blood and again come to a liver where they are exposed to a rekonjyugation and are emitted with bile (so-called intra hepatic circulation of substances).
Glands of a stomach from an organism remove the organic bases (e.g., aniline) high-ionized at usual pH of a gastric juice. Weak organic to - you and the bases high-ionized at normal pH of intestinal juice, apparently, are allocated from an organism through intestines. Release of some toxic agents in not ionized look happens in insignificant degree through salivary, sweat, mammary glands.
Allocation through lungs with expired air is the main way of removal from an organism of volatile lipophilic compounds, napr, chlorinated hydrocarbons (perchloromethane, tetrachlorethylene, etc.) which are metabolized in small degree and are emitted through lungs preferential in not changed look.
Of alien substances from among pharmaceuticals is carried out by the same principles, as D. of connections of other origin (see. Pharmacokinetics ).
Bibliography: Park D. B. Biochemistry of alien connections, the lane with English, M., 1973; The Guide to toxicology of toxic agents, under the editorship of G. N. Golikova, M., 1972; Trin at with F. P., To and r with e of N'ko V. V. and Kundiyev Yu. I. Absorption of pesticides through skin and prevention of poisonings, Kiev, 1975; Csaky T. Z. Introduction to general pharmacology, N. Y., 1969; Deichmann W. B. a. G e r a r d e H. W. Toxicology of drugs and chemicals, N. Y. — L., 1969; S with h e 1 e r W. Grundlagen der allgemeinen Pharma-kologie, Jena, 1969, Bibliogr.
B. K. Muratov, And. B. Sanotsky.