Stress is considered a non-specific reaction of the body to the action of internal or external factors. This definition was put into practice by G. Selye (a 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 body's reaction.
Distinguishing Features
When analyzing the reaction, the nature of the situation (whether it is pleasant or unpleasant) in which the organism is located does not matter. What is of interest is the intensity of the need to adapt or restructure according to the conditions. The organism first of all opposes the influence of the irritating agent with its ability to respond and adapt flexibly to the situation. Accordingly, the following conclusion can be drawn. Stress is a set of adaptive responses produced by the body in the event of the influence of a factor. This phenomenon is called in science the general adaptation syndrome.
Stages
Adaptation Syndromeproceeds in stages. First comes the stage of anxiety. The organism at this stage expresses a direct reaction to the impact. The second stage is resistance. At this stage, the body most effectively adapts to the conditions. The final stage is exhaustion. To pass the previous stages, the body uses its reserves. Accordingly, by the last stage they are significantly depleted. As a result, structural changes begin inside the body. However, in many cases this is not enough for survival. Accordingly, irreplaceable energy reserves are depleted, and the body ceases to adapt.
Oxidative stress
Antioxidant systems and prooxidants under certain conditions come into an unstable state. The composition of the latter elements includes all the factors that play an active role in the enhanced formation of free radicals or other types of oxygen of the reactive type. The primary mechanisms of the damaging effect of oxidative stress can be represented by different agents. These can be cellular factors: defects in mitochondrial respiration, specific enzymes. The mechanisms of oxidative stress can also be external. These include, in particular, smoking, medication, air pollution, and so on.
Free radicals
They are constantly formed in the human body. In some cases, this is due to random chemical processes. For example, hydroxyl radicals (OH) are formed. Their appearance is associated withconstant exposure to low-level ionizing radiation and the release of superoxide due to the leakage of electrons 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 free radical formation and response expression by the body are approximately balanced. In this case, it is quite easy to shift this relative equilibrium in favor of the radicals. As a result, cell 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 of reparative structures in the cells. They identify and remove damaged molecules. New elements take their place. In addition, cells have the ability to enhance protection by responding to oxidative stress. For example, rats placed in conditions with pure oxygen die after a few days. It is worth saying that about 21% O2 is present in ordinary air. If animals are exposed to gradually increasing doses of oxygen, their protection will be enhanced. As a result, it is possible to achieve that rats will be able to tolerate 100% concentration of O2. However, severe oxidative stress can cause severe damage or cell death.
Provoking factors
As mentioned above, the body maintains a balance of free radicals and protection. From this it can be concludedthat oxidative stress is caused by at least two causes. 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.
Decreased defensive reaction
It is known that the antioxidant system is more dependent on normal nutrition. Accordingly, we can conclude that a decrease in protection in the body is a consequence of a poor diet. In all likelihood, many human diseases are caused by a deficiency of antioxidant nutrients. For example, neurodegeneration is detected due to insufficient intake of vitamin E in patients whose body cannot absorb fats properly. There is also evidence that glutathione reduced in lymphocytes in extremely low concentrations is detected in people infected with HIV.
Smoking
It is one of the main factors that provoke 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 irritates the microphages of the lungs, resulting in the formation of superoxide. There are more neutrophils in the lungs of smokers than non-smokers. People who abuse tobacco are often malnourished and consume alcohol. Accordingly, their protection is weakened. Chronic oxidative stress provokes severe disorders of cellular metabolism.
Changes in the body
Different markers of oxidative stress are used for diagnostic purposes. These or other changes in the body indicate a specific site of the violation and the factor that provoked it. When studying the processes of formation of free radicals in the development of multiple sclerosis, the following indicators of oxidative stress are used:
- Malonic dialdehyde. It acts as a secondary product of free radical oxidation (FRO) 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 to calcium ions. An increase in the concentration of malondialdehyde during primary and secondary progressive multiple sclerosis confirms the first stage of oxidative stress - the activation of free radical oxidation.
- Schiff base is the end product of CPO proteins and lipids. An increase in the concentration of Schiff bases confirms the tendency for the activation of free radical oxidation to be chronic. With an increased concentration of malondialdehyde in addition to this product in primary and secondary progressive sclerosis, the onset of a destructive process may be noted. It consists in fragmentation and subsequent destruction of membranes. Elevated Schiff bases also indicate the first stage of oxidative stress.
- Vitamin E. It is a biological antioxidant that interacts with free radicals of peroxides and lipids. As a result of the reactions, ballast products are formed. Vitamin E is oxidized. He is consideredeffective neutralizer of singlet oxygen. A decrease in the activity of vitamin E in the blood indicates an imbalance in the non-enzymatic link of the AO3 system - in the second block in the development of oxidative stress.
Consequences
What is the role of oxidative stress? It should be noted that not only membrane lipids and proteins are affected, but also carbohydrates. In addition, changes begin in the hormonal and endocrine systems. The activity of the enzyme structure of thymus lymphocytes decreases, the level of neurotransmitters increases, and hormones begin to be released. Under stress, the oxidation of nucleic acids, proteins, carbons begins, and the total content of lipids in the blood increases. The release of adrenocorticotropic hormone is enhanced due to the intensive breakdown of ATP and the occurrence of cAMP. The latter activates protein kinase. It, in turn, with the participation of ATP, promotes the phosphorylation of cholinesterase, which transforms cholesterol esters into free cholesterol. Strengthening the biosynthesis of protein, RNA, DNA, glycogen with simultaneous mobilization from the depot of fats, the breakdown of fatty (higher) acids and glucose in tissues also causes oxidative stress. 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 basal metabolism - growth and differentiation of tissues, protein, lipid, carbohydrate metabolism. Glucagon and insulin play an important role. According to some experts, glucoseacts as a signal for the activation of adenylate cyclase, and cMAF for the production of insulin. All this leads to an intensification of the breakdown of glycogen in the muscles and liver, a slowdown in the biosynthesis of carbohydrates and proteins, and a slowdown in the oxidation of glucose. A negative nitrogen balance develops, the concentration of cholesterol and other lipids in the blood increases. Glycagon promotes the formation of glucose, inhibits its breakdown to lactic acid. At the same time, its overexpenditure leads to increased gluconeogenesis. This process is the synthesis of non-carbohydrate products and glucose. The first are pyruvic and lactic acids, glycerol, as well as any compounds that, during 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. The key role in the transformation of carbohydrates belongs to glucose-6-phosphate. This compound sharply slows down the process of phospholiritic breakdown 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 gluconeogenesis enzymes. This is especially true for phosphoenolpyruvate carboxykinase. It determines the rate of the process in the kidneys and liver. The ratio of gluconeogenesis and glycolysis shifts to the right. Glucocorticoids act as inducers of enzymatic synthesis.
Ketonebody
They act as a kind of fuel supplier for the kidneys, muscles. Under oxidative stress, the number of ketone bodies increases. They function as a regulator preventing excess mobilization of fatty acids from the depot. This is due to the fact that energy hunger begins in many tissues due to the fact that glucose, due to a lack of insulin, is not able to penetrate the cell. At high plasma concentrations of fatty acids, their absorption by the liver and oxidation increase, and the intensity of triglyceride synthesis increases. All this leads to an increase in the number of ketone bodies.
Extra
Science knows such a phenomenon as "plant oxidative stress". It is worth saying that the question of the specificity of the adaptation of cultures to various factors remains debatable today. Some authors believe that under unfavorable 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 crops is determined by specific responses. That is, the reaction is adequate to the factor. Meanwhile, most scientists agree that along with non-specific responses, specific ones also appear. At the same time, the latter cannot always be identified against the background of numerous universal reactions.
