Lalymenko O. Scientific substantiation of criteria for biological monitoring of an antidiabetic agent, a succinic acid derivative (an experimental study).

This thesis paper deals with a comprehensive toxicological and hygienic study of an original antidiabetic agent - succinic acid derivative. The thesis paper research used approaches of biological monitoring of xenobiotics and experimental revealing pathognomonic criteria of an adverse effect of the studied compound on the organism of experimental animals in different routes of intake and duration of the action. The thesis paper provides a scientific substantiation for exposure tests and biomarkers of the effect as criteria for the biological monitoring of the succinic acid derivative. The peculiarities of the antidiabetic agent toxicokinetics in the conditions of single administration are as follows: a prolonged stay of the antidiabetic agent and its metabolites in the systemic blood flow, the most pronounced in the inhalation, as well as the prevalence of biotransformation processes over the excretion of the compound. The peculiarities of toxicokinetics in subchronic intake are as follows: high concentrations of antidiabetic agent and the metabolite of ?-PhESA in the blood plasma at the beginning and end of the intragastric administration, in inhalation action at Limac level - the prevalence of antidiabetic agent content, at Limch level - the prevalence of ?-PhESA levels in the blood plasma. It is proved that the concentrations of the antidiabetic agent and its metabolites in blood plasma are the tests of exposure of subchronic effect of the studied compound. The increase of lipid hydroperoxide levels (in the blood serum, liver homogenate), the decrease of level of nitrite-anions (blood plasma and urine), and the decrease in activity of catalase, nitric oxide synthases and glutathione peroxidase (liver homogenate, erythrocyte hemolysate) were the biomarkers of the antidiabetic agent effect. The value of biological safe level of the antidiabetic agent effect in the blood plasma is scientifically substantiated at the level of 11 ng/µL.