FABOMOTIZOLE AS MEANS OF PHARMACOLOGICAL CORRECTION OF PRE- AND POSTNATAL DISTURBANCES INDUCED BY PEAT SMOKE POLLUTION, TOBACCO SMOKE, ALCOHOL, HYPERGLYCEMIA AND CYCLOPHOPHAMIDE IN THE DEVELOPMENT OF OFFSPRING OF RATS

DOI: https://doi.org/10.29296/24999490-2020-03-05

A.S. Solomina, O.V. Shreder, E.D. Mokrova, V.V. Zabrodina, D.M. Gorbatova, L.G. Kolik, A.D. Durnev Research Zakusov Institute of Pharmacology, Baltiyskaya Street, 8, Moscow, 125315, Russian Federation Е-mail: [email protected]

Introduction. Influence of environmental hazards on pregnant women or development of pregnancy in presence of pathogenic pathway may lead to miscarriage, teratogenic effects and/or significant abnormalities in physical development, cognitive and behavioral state observed in offspring. Prevention and correction of pre- and postnatal disturbances is the problem of high priority in modern pharmacology. The aim of the study. Influence of fabomotizole on pre- and postnatal abnormalities in the development of rat offspring exposed to peat smoke pollution, passive tobacco smoking, ethanol intake, gestational diabetes and cyclophosphamide-induces teratogenesis in compliant experimental models was studied. Methods. Fabomotizole was administered orally during pregnancy or before sampling of biomaterial in the dose range of 1 to 100 mg/kg. The level of DNA damage in placenta and fetus cells was assessed at the 13th day of pregnancy, parameters of embryonic development were observed on the 20th day of pregnancy, the unconditional reflexes formation and muscle tone were evaluated at 5th day of postnatal life and the cognitive functions of the same offspring were measured at the age of 2–3 months. Results. Fabomotizole in the range of therapeutic doses demonstrated the ability to reduce and/or fully eliminate DNA-damage in embryonic tissues, decrease the number of fetuses with external abnormalities, malformations of internal organs and skeletal system and corrected the disturbances in sensory-motor activity, behavior and cognitive functions resulted from negative impact of several factors. Conclusions. Protective action of fabomotizole can be connected with antimutagenic, antioxidative and neuroprotective properties due to its interaction with sigma-1 and MT1 receptors.
Keywords: 
fabomotizole, sigma receptor, pre- and postnatal development, rats

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