Kudrya M. Ya.1, Lalimenko O. S.1, Zavgorodnii I. V.2, Melnikovskaya N. V.1, Ustenko N. V.1, Shalamay A. S.3
THE STATE OF PRO-ANTIOXIDANT HOMEOSTASIS AND METABOLISM OF NITRIC OXIDE UNDER A SUBCHRONIC EFFECT OF SUCCINIC ACID DERIVATIVE
1V.Y. Danilevsky Institute of Endocrine Pathology Problems, NAMS of Ukraine, Kharkiv
2Kharkiv National Medical University
3PJSC SIC "Borshchahivskiy CPP", Kiev
Full article (PDF), RUS
Introduction. The analysis of literature showed that in order to improve the accuracy of risk assessment of drugs’ impact on the human body and reliability of workers’ protection in the corresponding production it is necessary to ground a biological maximum permissible concentration (BMPC) of a specific drug.
Purpose of the study. To define a criterion value of the nitric oxide exchange, lipid peroxidation and antioxidant protection as biomarkers of the effect of a succinate-containing antidiabetic agent, when grounding a biologically maximum permissible concentration.
Materials and methods. Experiments were conducted on 42 male rats, which received an aqueous emulsion of an antidiabetic agent, derivative of succinic acid β-PhEA-OSA, intragastric - 30 times, in the dose of 100 mg. The state of processes: lipid peroxide oxidation by the level of diene conjugates, lipid hydroperoxides and active products, reacting with thiobarbituric acid, antioxidant protection by enzymes glutathione activity as well as catalase and superoxide dismutase activities. The state of nitric oxide metabolism was evaluated by the level of nitrite / nitrate anions with a spectrophotometry method, using a Griess reagent and activity of NO-synthase (c-NOS) by a kinetic method.
Results. In conditions of a subchronic administration of β-PhEA-OSA substance the changes in the system of lipid peroxidation and antioxidant protection were observed at early stages, which were of an adaptive character. When lengthening the term of the experiment an activation of certain lipid peroxidation reactions in the blood and liver tissue was taken place as well as the decrease in the activity of the total of NO-synthase, products of stable terminal NO metabolites in blood plasma, urine and liver tissue of animals.
Conclusions. The biomarkers of the effect of the mentioned compound have been defined, which can be used for grounding biologically maximum permissible concentrations.
Key words: antidiabetic drug, pro-antioxidant homeostasis, nitrogen oxide
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