Stress is a nonspecific reaction of an organism 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 provoke stress. However, one factor cannot be distinguished and called its main cause of the reaction of the organism.
Features
When analyzing the reaction, the nature of the situation (pleasant or unpleasant) in which the body is located does not matter. Of interest is the intensity of the need for adaptation or restructuring in accordance with the conditions. The body primarily contrasts the influence of an irritating agent with its ability to respond and flexibly adapt to the situation. Accordingly, we can draw the following conclusion. Stress is a complex of adaptive responses issued by the body in the event of a factor. This phenomenon is called in science the general adaptive syndrome.
Stages
Adaptation syndrome proceeds in stages. First comes the stage of anxiety. The body at this stage expresses a direct reaction to the impact. The second stage is resistance. At this stage, the body adapts to the conditions as efficiently as possible. At the last stage, exhaustion sets in. To go through the previous stages, the body uses its reserves. Accordingly, to the last stage they are significantly depleted. As a result, structural changes begin within the body. However, in many cases this is not enough for survival. Accordingly, irreplaceable reserves of energy are depleted, and the body ceases to adapt.
Oxidative stress
Under certain conditions, antioxidant systems and prooxidants become unstable. 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. The primary mechanisms of the damaging effects of oxidative stress can be represented by different agents. These may be cellular factors: defects in mitochondrial respiration, specific enzymes . The mechanisms of oxidative stress can be external. These include 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. So, for example, hydroxyl radicals (OH) arise. Their appearance is associated with a constant exposure to low-level ionizing radiation and the release of superoxide due to 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 .
Oxidative stress mechanisms
The processes of the appearance of free radicals and the expression of the body's response are approximately balanced. Moreover, it is easy enough to shift this relative equilibrium in favor of radicals. As a result, cell biochemistry is disturbed 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 detect and remove damaged molecules. In the place of the latter come new elements. In addition, cells have the ability to enhance protection by responding to oxidative stress . For example, rats placed in pure oxygen conditions die several days later. It is worth saying that about 21% O 2 is present in ordinary air. If animals are exposed to gradually increasing doses of oxygen, their protection will be enhanced. As a result, rats will be able to tolerate a 100% concentration of O 2 as well . However, severe oxidative stress can cause serious destruction or cell death.
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Provocative factors
As mentioned above, the body maintains a balance of free radicals and protection. From this we can conclude that oxidative stress is caused by at least two reasons. The first is to reduce the activity of the defense. The second is to increase the formation of radicals to such an extent that antioxidants will not be able to neutralize them.
Decrease in protective reaction
It is known that the antioxidant system is more dependent on proper 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 in individuals infected with HIV, glutathione restored in lymphocytes in extremely low concentrations is detected.
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 is irritating to microphages of the lungs, as a result of which superoxide is formed. Smokers have more neutrophils in their lungs than non-smokers. People who abuse tobacco often eat poorly and consume alcohol. Accordingly, their protection is weakened. Chronic oxidative stress provokes severe disturbances in 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 site of the violation and the factor that provoked it. When studying the processes of free radical formation during the development of multiple sclerosis, the following oxidative stress indicators are used:
- Malondialdehyde. 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 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's base is the final 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 become chronic. With an increased concentration of malondialdehyde in addition to this product, with the primary and secondary progressive sclerosis, the onset of the destructive process can be noted. It consists in the fragmentation and subsequent destruction of the membranes. The increased content of Schiff bases also indicates 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 reactions, ballast products are formed. Vitamin E is oxidized. It is considered an effective neutralizer of singlet oxygen. A decrease in the activity index of vitamin E in the blood indicates an imbalance in the non-enzymatic link of the AO3 system - in the second block of the development of oxidative stress.
Effects
What is the role of oxidative stress ? It is worth noting that not only membrane lipids and proteins are exposed, 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, hormones begin to be released. Under stress, the oxidation of nucleic acids, proteins, carbons begins, and the total content of lipids in the blood rises. The release of adrenocorticotropic hormone increases due to the intense breakdown of ATP and the occurrence of cAMP. The latter activates protein kinase. It, in turn, with the participation of ATP promotes the phospholation of cholinesterase, which transforms cholesterol esters into free cholesterol. Strengthening the biosynthesis of protein, RNA, DNA, glycogen while mobilizing fat from the depot, and 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. An increase in the action of thyroid hormones is also noted. 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 the production of insulin. All this leads to intensification of the breakdown of glycogen in the muscles and liver, slowing down the biosynthesis of carbohydrates and proteins, slowing down the oxidation of glucose. A negative nitrogen balance develops, and the concentration of cholesterol and other lipids in the blood increases. Glycagon promotes the formation of glucose, inhibits its breakdown to lactic acid. Moreover, its overspending leads to increased gluconeogenesis. This process is a synthesis of non-carbohydrate products and glucose. The first ones are pyruvic and lactic acids, glycerol, as well as any compounds that, when catabolized, can transform into pyruvate or one of the intermediate elements of the tricarboxylic acid cycle.
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The main substrates are also amino acids and lactate. A key role in the transformation of carbohydrates belongs to glucose-6-phosphate. This compound drastically slows down the process of phospholithic digestion 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, an increase in the synthesis of gluconeogenesis enzymes is noted. This is especially true for phosphoenolpyruvate carboxykinase. It determines the speed of the process in the kidneys and liver. The ratio of gluconeogenesis and glycolysis is shifted to the right. Glucocorticoids act as inducers of enzymatic synthesis.
Ketone bodies
They act as a kind of suppliers of fuel for the kidneys, muscles. With oxidative stress, the number of ketone bodies increases. They function as a regulator to prevent excessive mobilization of fatty acids from the depot. This is due to the fact that in many tissues energy starvation begins due to the fact that glucose due to lack of insulin is not able to penetrate into the cell. With a high concentration of fatty acids in the plasma, their absorption by the liver and oxidation increase, and the intensity of the synthesis of triglycerides increases. All this leads to an increase in the number of ketone bodies.
Additionally
Science knows the phenomenon of oxidative stress in plants. 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 adverse conditions, the complex of reactions is universal. Its activity does not depend on the nature of the factor. Other experts argue that crop sustainability is determined by specific responses. That is, the reaction is adequate to the factor. Meanwhile, most scientists agree that, along with nonspecific answers, specific ones also appear. Moreover, the latter can not always be detected against the background of numerous universal reactions.