抄録
Prevention and correction of pre- and postnatal disturbances caused by various adverse factors is problem of high priority. Unique spectrum of pharmacological activity of sigma-1, MT1 and MT3 receptor agonist fabomotizole developed as potent anxiolytic in Russia with cytoprotective, neuroprotective and antioxidative properties allows supposing its ability to reduce and/or prevent pre- and postnatal abnormalities.
Experiments were carried out in outbred pregnant rats with several experimental models of cyclophosphamide-induced teratogenesis (20 mg/kg, i.p. on the 14th day of pregnancy), tobacco smoking (4 cigarettes with 13 mg tar and 1 mg nicotine from 1 to 19 days of pregnancy), ethanol (4,3 ml/kg, 40 % vol., per os from 10 to 19 days of pregnancy), peat smoke pollution (forced inhalation of mixture consisting of 70 % peat and 30 % wood pulp) and streptozotocin-induced diabetes (40 mg/kg, i.p. on the 1st day of pregnancy). The level of adverse impact under these models was characterized by significant genotoxic, embryotoxic and teratogenic effects as well as cognitive disturbances in the offspring. Fabomotizole (1-100 mg/kg) was administered per os. The level of DNA damage in placenta and fetus cells was assessed on the 13th day of pregnancy, parameters of embryonic development were evaluated on the 20th day of pregnancy and the cognitive functions of offspring were measured in behavioral tests at the age of 60 days.
Exposure to such toxic factors resulted in significant increase in DNA damage in placenta and fetus tissues, morphological anomalies and cognitive disorders in the offspring. DNA damage induced by cyclophosphamide, peat smoke and diabetes was 2-3 smaller when combined with fabomotizole. Genotoxic effects of tobacco smoke and ethanol were reduced to the level of control. Number of fetuses with external defects, abnormal internal organs and impaired ossification was decreased by fabomotizole. Behavior of rats treated with fabomotizole in "T-maze", "extrapolations escape" test "elevated plus-maze" were closer to control group.
Pre- and postnatal abnormalities of offspring exposed to various toxic agents can be connected with oxidative stress. Fabomotizole demonstrated the ability to reduce and/or prevent developmental disturbances due to its cytoprotective, neuroprotective and antioxidative properties associated with multitarget effects.
