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199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

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«
Vol. 23, Art. 24 (pp. 369-384)    |    2022       
»

Experimental substantiation of the use of glutathione metabolism indicators in laboratory diagnostics of the risk of developing contrast-induced nephropathy against the background of diabetes mellitus
S.N. Zheregelya1, S.I. Glushkov,2, A.I. Karpishchenko2

St. Petersburg State Pediatric Medical University
Pavlov First Saint Petersburg State Medical University



Brief summary

Background. The overall risk of developing contrast-induced nephropathy during a study using contrast does not exceed 2%, but increases to 20-40% in patients with diabetes mellitus, congestive heart failure, chronic kidney disease and the elderly. In addition, the occurrence of contrast-induced nephropathy after cardiac catheterization procedures is associated with hospital mortality of up to 20% and mortality within a year of up to 66% and higher in patients who required dialysis. Objective.To determine the contribution of changes in glutathione metabolism to the mechanisms of formation of contrast-induced nephropathy to optimize measures for their prevention, diagnosis and treatment. Materials and methods. In a study conducted on 200 white mongrel male rats, the dynamics of changes in the concentration of reduced glutathione, malondialdehyde, as well as the activity of antioxidant defense enzymes (glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase and catalase) in kidney tissues and in erythrocytes of laboratory animals under the conditions of intoxication with an X-ray contrast preparation against the background of experimental (alloxane) diabetes mellitus were determined. Results. The triggering pathogenetic factor in the development of contrast-induced nephropathy is the summation of the depressing effects of diabetes mellitus and radiopaque drugs on the activity of glucose-6-phosphate dehydrogenase and glutathione reductase in kidney tissues, leading to a decrease in the concentration of reduced glutathione and violations of thiol-disulfide equilibrium. The consequence of this may be a decrease in the activity of thiol-dependent enzymes, and then a violation of a number of cellular functions. Disorders of glutathione metabolism are detected even against the background of maintaining the concentration of standard indicators for assessing kidney function (urea and creatinine in blood serum) at the level of intact control. All this indicates that the study of the state of the glutathione system (primarily, the activity of glucose-6-phosphate dehydrogenase and glutathione reductase) in blood cells are highly sensitive methods. Conclusion. Violations of glucose-6-phosphate dehydrogenase and glutathione reductase activity in kidney tissues can be considered as a trigger pathogenetic factor in the realization of nephrotoxic effects of radiopaque drugs. Determination of glucose-6-phosphate dehydrogenase and glutathione reductase activity in erythrocytes is a promising, highly sensitive, pathogenetically based laboratory method for assessing the risk and severity of contrast-induced nephropathy.


Key words

Contrast-induced nephropathy, glucose-6-phosphate dehydrogenase, glutathione reductase, alloxan diabetes mellitus, glutathione, radiopaque drugs.





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