Oxidative stress: role, mechanism, indicators

Stress is considered a nonspecific reaction of the body to the action of internal or external factors. This definition was introduced into the practice of G. Selye (Canadian physiologist). Any action or condition can trigger stress. However, it is impossible to single out one factor and call it the main cause of the reaction of the organism.

Features

In the analysis of the reaction, the nature of the situation (whether pleasant or unpleasant) in which the organism is located does not matter. Interest is the intensity of the need for adaptation or restructuring in accordance with the conditions. The organism first of all opposes to the influence of the irritant agent its ability to respond and adapt flexibly to the situation. Accordingly, we can draw the following conclusion. Stress is a set of adaptive responses given by the body in the event of a factor. This phenomenon is called in science a common adaptation syndrome.

Stages of

Adaptation syndrome proceeds in stages. First comes the stage of anxiety. The organism at this stage expresses a direct reaction to the effect. The second stage is resistance. At this stage, the body is most effectively adapted to the conditions. At the last stage, exhaustion begins. For the passage of previous stages, the body uses its reserves. Accordingly, to the last stage they are considerably depleted. As a result, structural changes begin in the body. However, in many cases this is not enough for survival. Accordingly, irreplaceable energy reserves are depleted, and the body no longer adapts.

Oxidative stress

и прооксиданты при тех или иных условиях приходят в неустойчивое состояние. Antioxidant systems and pro- oxidants under certain conditions come to an unstable state. The composition of the latter elements includes all factors that play an active role in the enhanced formation of free radicals or other types of reactive oxygen. могут быть представлены разными агентами. Primary mechanisms of the damaging effect of oxidative stress can be represented by different agents. These can be cellular factors: defects of mitochondrial respiration, specific enzymes . могут быть и внешними. Mechanisms of oxidative stress can also be external. These, in particular, include smoking, taking medication, air pollution and so on.

Free Radicals

They are constantly formed in the human body. In some cases this is due to accidental chemical processes. For example, hydroxyl radicals (OH) appear. Their appearance is associated with a constant exposure to low-level ionizing radiation and the release of superoxide due to electron leakage and their transport chain. In other cases, the appearance of radicals is due to the activation of phagocytes and the production of nitric oxide by endothelial cells.

Mechanisms of oxidative stress

The processes of the formation of free radicals and the expression of the body response are approximately balanced. It is quite easy to shift this relative equilibrium to the benefit of radicals. . As a result, the cell's biochemistry is disrupted and oxidative stress occurs. Most of the elements are able to tolerate a moderate degree of imbalance. This is due to the presence in the cells of the reparative structures. They detect and remove damaged molecules. In place of the latter, new elements come. . In addition, cells have the ability to enhance protection, responding to oxidative stress . For example, rats placed in conditions with pure oxygen die after a few days. It is worth saying that in ordinary air there is about 21% of O ₂ . If you act on animals gradually increasing doses of oxygen, their protection will increase. As a result, it can be achieved that rats will be able to tolerate 100% O ₂ concentration. способен вызвать серьезные разрушения или гибель клеток. Nevertheless, strong oxidative stress can cause serious damage or cell death.

The provoking factors

As stated above, the body maintains a balance of free radicals and protection. вызывается как минимум двумя причинами. From this we can conclude that oxidative stress is caused by at least two reasons. The first is to reduce the protection activity. The second is to increase the formation of radicals to such an extent that antioxidants will not be able to neutralize them.

Reduction of the protective reaction

It is known that the antioxidant system is more dependent on normal nutrition. Accordingly, it can be concluded that a decrease in protection in the body is a consequence of a poor diet. In all probability, many human diseases are caused by a deficit of antioxidant nutrients. For example, neurodegeneration is detected due to insufficient intake of vitamin E in patients whose body can not properly metabolize fats. There is also information that in persons infected with HIV, glutathione restored in lymphocytes is detected in extremely low concentrations.

Smoking

It is one of the main factors provoking oxidative stress in the lungs and many other tissues of the body. Smoke and tar are rich in radicals. Some of them are able to attack molecules and reduce the concentration of vitamins E and C. Smoke has an irritating effect on the microphages of the lungs, resulting in the formation of superoxide. In the lungs of smokers there are more neutrophils than non-smokers. People who abuse tobacco often do not eat well and consume alcohol. Accordingly, their protection is weakened. провоцирует тяжелые нарушения клеточного метаболизма. Chronic oxidative stress provokes severe disorders of cellular metabolism.

Changes in the body

For diagnostic purposes, various markers of oxidative stress are used. These or other changes in the body indicate a specific area of the disorder and the factor that provoked it. : When studying the formation of free radicals in the development of multiple sclerosis, such indicators of oxidative stress are used :

1. Malon dialdehyde. It acts as a secondary product of free radical oxidation (CPO) of lipids and has a damaging effect on the structural and functional state of membranes. This, in turn, leads to an increase in their permeability for calcium ions. The increase in the concentration of malonic dialdehyde during primary and secondary progressive multiple sclerosis confirms the first stage of oxidative stress - the activation of free radical oxidation.
2. The basis of Schiff is the final product of CPO proteins and lipids. An increase in the concentration of Schiff bases confirms the tendency of the activation of free radical oxidation to be chronically activated. With an increased concentration of malonic dialdehyde in addition to this product, primary and secondary-progressive sclerosis may mark the onset of a destructive process. It consists in fragmentation and subsequent destruction of membranes. The elevated content of Schiff bases also indicates the first stage of oxidative stress.
3. Vitamin E. It is a biological antioxidant interacting with free radicals of peroxides and lipids. As a result of reactions, ballast products are formed. Vitamin E is oxidized. It is considered an effective neutralizer of singlet oxygen. A decrease in the index of vitamin E activity in the blood indicates an imbalance in the non-enzymatic link of the AO3 system - in the second block of oxidative stress development.

Effects

? What is the role of oxidative stress ? It is worth noting that not only the lipids of membranes and proteins but also carbohydrates are affected. In addition, changes begin in the hormonal and endocrine systems. The activity of the enzyme structure of the thymus lymphocytes decreases, the level of neurotransmitters rises, hormones begin to release. When stress begins, oxidation of nucleic acids, proteins, carbons, increases the total content of lipids in the blood. The release of adrenocorticotropic hormone is intensified due to the intense disintegration of ATP and the appearance of cAMP. The latter activates protein kinase. It, in turn, with the participation of ATP promotes the phospholysis of cholinesterase, which transforms cholesterol esters into free cholesterol. Strengthening the biosynthesis of protein, RNA, DNA, glycogen with simultaneous mobilization from depot fat, decay in tissues of fatty acids (higher) acids and glucose also causes oxidative stress. считается одним из наиболее серьезных последствий процесса. Aging is considered one of the most serious consequences of the process. There is also an increase in the action of thyroid hormones. It provides regulation of the rate of basic metabolism - growth and differentiation of tissues, protein, lipid, carbohydrate metabolism. An important role is given to glucagon and insulin. According to some experts, glucose acts as a signal for the activation of adenylate cyclase, and cMAF for insulin production. All this leads to intensification of the decomposition of glycogen in muscles and liver, slowing down the biosynthesis of carbohydrates and proteins, and slowing down the oxidation of glucose. A negative nitrogen balance develops, the concentration of cholesterol and other lipids in the blood increases. Glikagon promotes the formation of glucose, inhibits its decay to lactic acid. At the same time, its over-expenditure leads to an increase in gluconeogenesis. This process is a synthesis of non-carbohydrate products and glucose. The first are pyruvic and lactic acids, glycerol, as well as any compounds that, under catabolism, can be transformed into pyruvate or one of the intermediate elements of the tricarboxylic acid cycle. The main substrates are also amino acids and lactate. A key role in the transformation of carbohydrates belongs to glucose-6-phosphate. This compound dramatically slows down the process of phosphoryltic cleavage of glycogen. Glucose-6-phosphate activates the enzymatic transport of glucose from uridine diphosphoglucose to synthesized glycogen. The compound also acts as a substrate for subsequent glycolytic transformations. Along with this, there is an increase in the synthesis of enzymes of gluconeogenesis. In particular, this is characteristic of phosphoenolpyruvate-carboxykinase. It determines the speed of the process in the kidneys and liver. The ratio of gluconeogenesis and glycolysis shifts to the right. As inducers of enzyme synthesis are glucocorticoids.

Ketone bodies

They act as a kind of fuel supplier for the kidneys, musculature. With oxidative stress, the amount of ketone bodies increases. They function as a regulator, preventing excessive mobilization of fatty acids from the depot. This is due to the fact that in many tissues the energy hunger begins due to the fact that glucose due to lack of insulin is unable to penetrate into the cell. With a high concentration of fatty acids in the plasma, their absorption by the liver increases and oxidation increases, and the intensity of triglyceride synthesis increases. All this leads to an increase in the number of ketone bodies.

Additionally

Science also knows such a phenomenon as "oxidative plant stress." It is worth saying that the issue of the specificity of the adaptation of cultures to various factors remains controversial today. Some authors believe that under adverse conditions the complex of reactions has a universal character. Its activity does not depend on the nature of the factor. Other experts argue that the resistance of cultures is determined by specific responses. That is, the reaction is adequate to the factor. Meanwhile, most scientists agree that together with nonspecific answers, specific ones also appear. At the same time, the latter can not always be detected against the background of numerous universal reactions.