Female outbred albino rats were daily subjected to forced inhalations of peat smoke (4 cores packed with a mixture of peat (70%) and wood pulp (30%); 0.46 g, pH ≥ 5.5) per se and in combination with oral afobazole (anxiolytic) on days 1-20 of pregnancy. Exposure to peat smoke inhibited body weight gain in pregnant rats, caused an increase of postimplantation deaths, reduction of fetal weights, and an increase in the number of hematomas and hemorrhages in fetuses. Afobazole in doses of 1 and 10 mg/kg reduced significantly the untoward effects of peat smoke on fetal development.
Female outbred albino rats were daily subjected to forced inhalations of peat smoke (4 cores packed with a mixture of peat (70%) and wood pulp (30%); 0.46 g, pH at least 5.5, core burning time 6 min,; total exposure 44 min) per se and in combination with oral afobazole (anxiolytic) in doses of 1 and 10 mg/kg on days 1-20 of pregnancy. Some groups of females received oral afobazole (200 mg/kg) after delivery, due to which their newborn rats received the drug in doses of 1-10 mg/kg with maternal milk on days 1-20 of life. Exposure to peat smoke inhibited body weight gain in the progeny on days 5-60 of life. Afobazole treatment during the pre- and postnatal periods prevented this effect. Open field testing showed that exposure to peat smoke prolonged the motor activity in the progeny and impaired the loss of orientation and exploratory behavior during repeated testing. Oral afobazole (1 and 10 mg/kg) during the prenatal and/or postnatal period (with maternal milk) prevented the effects of peat smoke.
Background. It was shown that prenatal exposure to peat smoke leads to disturbances of fetal and postnatal development in rats. Genotoxic mechanisms may be involved to these deleterious effects. The objective of the present study was to evaluate the DNA damage and its modification by known antimutagen afobazole in placenta and embryo of rats, exposed to peat smoke. Materials and methods. Pregnant rats were exposed to filtered air (control), to peat smoke or to peat smoke with receiving of afobazole (1 or 10 mg/kg, per os) for 44 min, daily during days 1 to 13 of gestation. At the day 13 four placenta and embryo samples from each rat were obtained for DNA damage analysis using the alkaline comet assay. Results. A significant, 4-5 folds increase in the DNA damage values (% DNA in tail) was found in placenta and embryos of rats exposed to peat smoke. Genotoxic effects were generally more pronounced in placenta. Exposure to peat smoke together with receiving of afobazole at the doses 1 and 10 mg/kg showed a significant, 53-60 % decrease in the mean % DNA in tail values in both placenta and embryos. Clear inter and intra-individual differences in genotoxic as well as in antigenotoxic effects were observed. For the some placenta or embryo samples were seen reducing of DNA damage to the control level. Conclusion. Exposure of pregnant rats to peat smoke causes DNA damage in placenta and embryos. This smoke-induced genotoxicity might be decreased or prevented by antimutagenic agents.
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.
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