Biomedical subjects
Publications and source records attributed to L F Shashkina.
System of calculating methods for staged prognostication of toxicometric parameters and hygienic standards of synthetic drugs was elaborated. This system gives possibility to substantiate quantitative criteria for determination of capacity and directions of investigations in pharmaceutical industry.
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Morphohistochemical study of an embryotoxic and teratogenic action of acetate of androstenolone, acetate of 16-dehydropregnenolone, and methyltestosterone applied dayly to the skin of white rats during the entire course of gestation was carried out. A marked embryotoxic effect of acetate of androstenolone has been established. The teratogenic effect of the agents under study manifested itself in impairment of the processes of differentiation of structural elements of organs and tissues, or in rough underdevelopment of foetuses on the whole (following the exposure to acetate of androstenolone). In addition, a decrease in contents of nucleic acids and proteins in tissues, as well as some disorders of the carbohydrate metabolism in different organs and tissues were noted. The authors recommend to use histological and histochemical methods in investigations of embryotropic action of low doses of steroids.
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Experiments were conducted on rats. A study was made of the reaction of target organs to the intramuscular injection of androgenic preparations--testosterone and its esters (acetate, propionate, phenylpropionate, isocapronate, enantate and caprinate) comparison with anabolic methylandrostendiol. An equation is presented for mathematical description of the dependence of the androgenic effect on the dose of the praparations injected, used in a wide range of doses. The equation coefficients proved to have a definite physiological sense.
The skin-resorptive action of testosterone and of its ethers (propionate, phenylpropionate, isocapronate, enantate, caprinate) was studied on castrated albino male rats with a one-time application to the skin. The effect was assessed by the growth of the seminal vesicles and the ventral lobe of the prostate. The highest skin-resorptive activity displayed testosterone-propionate and the lowest--testosterone-caprinate. The maximum effect following application of all the studied substances was registered on the 2-3d day. The amount of the maximum active dose (0,1 mg per animal) warrants including these compounds in a group of highly dangerous substances producing a skin-resorptive action.
The carcinogenic activity of spyrobromin was studied during the chronic experiment on 1.5-2-month-old rats and mice of both sexes. The drug was administered intragastrically and intraperitoneally once a week in the maximally tolerant dose for 24 months. Under the given experimental conditions spyrobromin can diminish the latent period of the development of tumours in the experimental rats at intraperitoneal administration. At intragastric administration of the drug no decrease was noted in the latent period and no increase of tumours was observed in the experimental groups of the animals as compared with control. Spyrobromin is considered to be a weak carcinogen. The oral route of administration is the most safe with respect to the oncogenic risk.
The effects of dispirotripiperazine derivatives spirobromin and prospidin on the parameters of the peripheral blood and behavioral reactions in a chronic 12-month experiment were studied. The experiment was performed on noninbred rats of both sexes. The maximal tolerated doses of the drugs were administered by two routes (intragastrically or intraperitoneally). Hemoglobin, erythrocytes, leukocytes, platelets, reticulocytes, eosinophils were determined in the blood. The behavioral reactions were registered by the methods of the "open field" and the "open area". Under the conditions of the chronic experiment spirobromin and prospidin were shown to exert no significant effect on the parameters of the peripheral blood except a decrease in the amount of erythrocytes. It was noted that spirobromin exerted the most pronounced toxic action on erythrocytes. As to the behavioral reactions, after the administration of prospidin, the neurotoxic action on the rats was found after 12-14 months of observation.
The antihistaminic drug dimebon was subjected to toxicological study. It was demonstrated that as regards the level of the mean lethal doses dimebon can be attributed to little toxic substances. Administration of the drug in the doses approximating the therapeutic ones (1 and 5 mg/kg) for 2 months did not produce any alterations in rats, guinea-pigs or dogs. When administered in high doses (10 and 70 mg/kg) the drug provoked compensated abnormalities of some functions of the liver and kidneys in the presence of moderate and reversible structural changes in these organs. Dimebon did not exert any local irritating effect on the gastrointestinal tract. Administration of the drug in doses of 150 and 300 mg/kg at different times of pregnancy (days 1-7, 8-13, 14-19) did not produce any embryolethal or teratogenic effects.