Dicarbonyl stress: the hypothesis of cell damage in conditions of hypoxia. The trigger mechanism for the development of multiorgan dysfunction
Background. Various critical states of the body are often associated with the development of hypoxia, as a result of which the mechanisms of glycolysis are activated, under the influence of stress hormone release, hyperglycemia develops. It is shown that under the conditions of anaerobic glycolysis against a background of hyperglycemia, toxic compounds are produced in the cells, which cause the glycosylation of proteins and nucleic acids. Together with the violation of the cellular protein function, mitochondrial dysfunction develops, which leads to an energy deficiency and organ dysfunction. The aim of investigation was to identify the main mechanisms of dicarbonyl stress, their importance for the formation of critical states of the organism and determine the most promising methods of correction for specialists in the field of intensive care. Materials and methods. Detailed study of the results of modern scientific researches on the processes of carbohydrate metabolism in pathological conditions based on information provided on the Internet. Results. The leading role in the damage to the cellular structures of the body under dicarbonyl stress belongs to glyoxal and methylglyoxal. These substances are formed as by-products of anaerobic glycolysis. Increase in their synthesis is promoted by activation of anaerobic glycolysis and hyperglycemia. Dicarbonyl compounds enter into chemical reactions with amino groups of proteins, nucleic acids and other biologically active compounds, disrupting their functioning. Natural detoxification is carried out by the glyoxalase system with the participation of reduced glutathione, which is the main component of the antioxidant system. The increase in oxidative stress and the appearance of antioxidant deficiency cause an increase in the severity of lesions associated with increased production of glyoxal and methylglyoxal. Prevention of dicarbonyl stress is achieved by increasing the power of the antioxidant system, primarily by increasing the production of reduced glutathione. To neutralize toxic dicarbonyl metabolites, drugs that perform the function of “traps” can be used. The use of therapy aimed at eliminating mitochondrial dysfunction is promising. Conclusions. The emerging problem of damage to the body in conditions of dicarbonyl stress dictates the need for the analysis and reassessment of a variety of intensive care interventions. A detailed study of the characteristics of carbohydrate metabolism in various critical states, including determination of glyoxal and methylglyoxal concentration, monitoring the level of glycemia and clearance of lactate, together with a return to assessing the state of compensation of the prooxidant/antioxidant system of the body, is one of the promising directions for upcoming scientific research in the clinic. Specialists in intensive care face daily situations where dicarbonyl stress can act as one of the real mechanisms for the formation of organ, multi-organ dysfunction and predetermine the development of decompensation of vital functions. Learning to resist him is the actual immediate task.
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