The body's antioxidant system

The body's antioxidant system is a set of mechanisms that inhibit autooxidation in the cell.

Non-enzymatic autooxidation, if not limited to a local outbreak, is a destructive process. Since the appearance of oxygen in the atmosphere, prokaryotes have needed constant protection from spontaneous reactions of oxidative decomposition of their organic components.

The antioxidant system includes antioxidants that inhibit autooxidation at the initial stage of lipid peroxidation (tocopherol, polyphenols) or active oxygen species (superoxide dismutase - SOD) in membranes. In this case, particles with an unpaired electron, tocopherol or polyphenol radicals formed during the reduction are regenerated by ascorbic acid contained in the hydrophilic layer of the membrane. Oxidized forms of ascorbate are in turn reduced by glutathione (or ergothioneine), which receives hydrogen atoms from NADP or NAD. Thus, radical inhibition is carried out by the glutathione (ergothioneine) ascorbate-tocopherol (polyphenol) chain, transporting electrons (as part of hydrogen atoms) from pyridine nucleotides (NAD and NADP) to SR. This ensures a stationary, extremely low level of free radical states of lipids and biopolymers in the cell.

Along with the AO chain, the free radical inhibition system in a living cell involves enzymes that catalyze the oxidation-reduction conversion of glutathione and ascorbate - glutathione-dependent reductase and dehydrogenase, as well as those that break down peroxides - catalase and peroxidases.

It should be noted that the functioning of two defense mechanisms - the chain of bioantioxidants and the group of antiperoxide enzymes - depends on the fund of hydrogen atoms (NADP and NADH). This fund is replenished in the processes of biological enzymatic oxidation-dehydrogenation of energy substrates. Thus, a sufficient level of enzymatic catabolism - an optimally active state of the body is a necessary condition for the effectiveness of the antioxidant system. Unlike other physiological systems (for example, blood coagulation or hormonal), even a short-term deficiency of the antioxidant system does not pass without a trace - membranes and biopolymers are damaged.

The breakdown of antioxidant protection is characterized by the development of free-radical damage to various components of the cell and tissues that make up the SR. The polyvalence of manifestations of free-radical pathology in different organs and tissues, the different sensitivity of cell structures to the effects of SR products indicate unequal provision of organs and tissues with bioantioxidants, in other words, apparently, their antioxidant system has significant differences. Below are the results of determining the content of the main components of the antioxidant system in different organs and tissues, which allowed us to draw a conclusion about their specificity.

Thus, the peculiarity of erythrocytes is the large role of antiperoxide enzymes - catalase, glutathione peroxidase, SOD, in congenital enzymopathies of erythrocytes, hemolytic anemia is often observed. Blood plasma contains ceruloplasmin, which has SOD activity, which is absent in other tissues. The presented results allow us to imagine the AS of erythrocytes and plasma: it includes both an antiradical link and an enzymatic defense mechanism. Such a structure of the antioxidant system allows us to effectively inhibit the FRO of lipids and biopolymers due to the high level of saturation of erythrocytes with oxygen. A significant role in limiting the FRO is played by lipoproteins - the main carrier of tocopherol, from them tocopherol passes into erythrocytes upon contact with membranes. At the same time, lipoproteins are most susceptible to autooxidation.

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Specificity of antioxidant systems of different organs and tissues

The initiating significance of non-enzymatic autooxidation of lipids and biopolymers allows us to assign a triggering role in the genesis of SP to the insufficiency of the body's antioxidant defense system. The functional activity of the antioxidant system of different organs and tissues depends on a number of factors. These include:

1. the level of enzymatic catabolism (dehydrogenation) - production of the NAD-H + NADP-H fund;
2. the degree of consumption of the NAD-H and NADPH fund in biosynthetic processes;
3. the level of reactions of enzymatic mitochondrial oxidation of NADH;
4. the supply of essential components of the antioxidant system - tocopherol, ascorbate, bioflavonoids, sulfur-containing amino acids, ergothioneine, selenium, etc.

On the other hand, the activity of the antioxidant system depends on the severity of the effects of lipids that induce free radical oxidation; when they are excessively active, inhibition is disrupted and the production of free radicals and peroxides increases.

In different organs, according to the tissue specificity of metabolism, certain components of the antioxidant system prevail. In extracellular structures that do not have a fund of NAD-H and NADPH, the influx of reduced forms of AO-glutathione, ascorbate, polyphenols, and tocopherol transported by the blood is of significant importance. Indicators of the level of provision of the body with AO, the activity of antioxidant enzymes, and the content of STO products integrally characterize the activity of the antioxidant system of the body as a whole. However, these indicators do not reflect the state of the AS in individual organs and tissues, which can differ significantly. The above allows us to assume that the localization and nature of free radical pathology are predetermined mainly by:

• genotypic features of the antioxidant system in different tissues and organs;
• the nature of the exogenous SR inducer acting throughout ontogenesis.

By analyzing the content of the main components of the antioxidant system in various tissues (epithelial, nervous, connective), it is possible to identify various variants of tissue (organ) systems of FRO inhibition, which generally coincide with their metabolic activity.

Erythrocytes, glandular epithelium

In these tissues, the active pentose phosphate cycle functions and anaerobic catabolism predominates; the main source of hydrogen for the antiradical chain of the antioxidant system and peroxidases is NADPH. Erythrocytes as oxygen carriers are sensitive to FRO inducers.

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Muscle and nervous tissue

The pentose phosphate cycle in these tissues is inactive; NADH, formed in the aerobic and anaerobic cycles of fat and carbohydrate catabolism, predominates as a source of hydrogen for antiradical inhibitors and antioxidant enzymes. The saturation of cells with mitochondria causes an increased risk of O2 "leakage" and the possibility of damage to biopolymers.

Hepatocytes, leukocytes, fibroblasts

Balanced pentose phosphate cycle and ana- and aerobic catabolic pathways are observed.

The intercellular substance of connective tissue is blood plasma, fibers and the ground substance of the vascular wall and bone tissue. Inhibition of SR in the intercellular substance is provided mainly by antiradical inhibitors (tocopherol, bioflavonoids, ascorbate), which causes high sensitivity of the vascular wall to their insufficiency. In addition to them, blood plasma contains ceruloplasmin, which has the ability to eliminate superoxide anion radical. In the lens, in which photochemical reactions are possible, in addition to antiradical inhibitors, the activity of glutathione reductase, glutathione peroxidase and SOD is high.

The presented organ and tissue features of local antioxidant systems explain the differences in the early manifestations of SP with different types of effects inducing FRO.

The different functional significance of bioantioxidants for different tissues predetermines differences in local manifestations of their deficiency. Only deficiency of tocopherol, a universal lipid antioxidant of all types of cellular and noncellular structures, manifests itself by early damage in different organs. Initial manifestations of SP caused by chemical prooxidants also depend on the nature of the agent. The data allow us to believe that along with the nature of the exogenous factor, the role of genotype-specific species and tissue-specific features of the antioxidant system is significant in the development of free radical pathology. In tissues with a low rate of biological enzymatic oxidation, such as the vascular wall, the role of the antiradical chain ergothioneine - ascorbate (bioflavonoids) - tocopherol, which is represented by bioantioxidants not synthesized in the body, is high; accordingly, chronic polyantioxidant deficiency primarily causes damage to the vascular wall. In other tissues, the role of enzymatic components of the antioxidant system prevails - SOD, peroxidases, etc. Thus, a decrease in the level of catalase in the body is characterized by progressive periodontal pathology.

The state of the antioxidant system in different organs and tissues is determined not only by the genotype, but also during oncogenesis by the phenotypically heterochronic decline in the activity of various components of the antioxidant system, caused by the nature of the inducer of the antioxidant system. Thus, in real conditions in an individual, different combinations of exogenous and endogenous factors of the breakdown of the antioxidant system determine both the general free-radical mechanisms of aging and the particular triggers of free-radical pathology, manifested in certain organs.

The presented results of the assessment of the activity of the main links of the AS in different organs and tissues are the basis for searching for new drugs-inhibitors of lipid FRO of targeted action for the prevention of free radical pathology of a certain localization. Due to the specificity of the antioxidant system of different tissues, AO drugs should perform the missing links differentially for a certain organ or tissue.

Different antioxidant systems were revealed in lymphocytes and erythrocytes. Gonzalez-Hernandez et al. (1994) studied the antioxidant systems in lymphocytes and erythrocytes in 23 healthy subjects. It was shown that in lymphocytes and erythrocytes the activity of glutathione reductase was 160 and 4.1 U/h, glutathione peroxidase - 346 and 21 U/h, glucose-6-phosphate dehydrogenase - 146 and 2.6 sd/h, catalase - 164 and 60 U/h, and superoxide dismutase - 4 and 303 μg/s, respectively.