Lalimenko O. S.
USING APPROACHES TO BIOLOGICAL MONITORING IN HYGIENIC REGULATION OF XENOBIOTICS
State Institution "V.Y. Danilevsky Institute of Endocrine Pathology Problems of the National Academy of Medical Sciences of Ukraine", Kharkiv
Full article (PDF), RUS
Introduction. In recent time in order to detect cause-effect relations between exposure to chemical factors and development of occupational diseases the biological monitoring is used.
Purpose of the study. Identification and substantiation of biomarkers of exposure and effect, as criteria of biological monitoring of an antidiabetic agent, a derivative of succinic acid.
Materials and methods. Experiments were conducted on 85 male rats. Peculiarities of toxicokinetics were studied in a single intragastric administration of the aqueous emulsion of the antidiabetic agent to rats in the dose of 100 mg. The subchronic exposure was studied in condition of intragastric (30-fold in the dose of 100 mg) and intranasal (20-fold in the dose of 6,7 and 1,0 mg/ml) administrations of the antidiabetic agent to experimental animals. The doses for intranasal administration were recalculated, according to the threshold of acute and chronic inhalation effects of the compound. The state of lipid peroxidation, antioxidant protection and nitric oxide metabolism was investigated. The chromatographic determination of the antidiabetic agent and its metabolites in blood plasma of experimental animals was conducted using a HPLC method.
Results. The toxicokinetic parameters in conditions of the single intragastric administration of the antidiabetic agent have been established. The antidiabetic agent quickly enters the blood and circulates there for a long time. We established that processes of biotransformation of the agent prevailed over its excretion. The concentration of the agent or its metabolites (2-HPhSA, β-PhESA) in blood plasma is biomarkers of exposure of this antidiabetic agent. The biomarkers of effect in the intragastric administration are: increase of lipid hydroperoxide levels in the blood serum, the decrease of levels of NO2-/NO3- in the blood plasma, glutathione peroxidase in the red blood cell hemolysate and c-NOS in the liver tissue. Biomarkers of the effect in intranasal administrations: increase of lipid hydroperoxide levels in the liver tissue, decrease of levels of NO2-/NO3- in blood plasma, glutathione peroxidase and c-NOS in blood red cell hemolysate.
Conclusion. The detected biomarkers of exposure (concentration of the antidiabetic agent and its metabolites in blood plasma and biomarkers of effect are limiting criteria of the effect of this compound on the body. These criteria should be taken into account for hygienic regulation of antidiabetic agents in the working zone air for improving the accuracy of risk assessment of the effect of the tested compounds on workers’ health.
Key words: biomonitoring, biomarkers of exposure and effect, antidiabetic agent
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