[Change of spermatogenesis in mature rats after long-term inhalation of small doses of methyltestosterone].
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Biomedical subjects
Publications and source records attributed to L V Nechushkina.
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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.
A study was made of the blastomogenic activity of dioxydin, a new antibacterial broad-action drug. Administration of dioxydin in doses of 20-100 mg/kg (exceeding 2-10-fold the therapeutic dose for humans) to mice and rats intragastrically for 18 months and intraperitoneally (2 years of observation) as well as combined administration of the drug to rats transplacentally and postnatally (1.5 years of observation) did not induce any neoplasms.
The first generation progeny of rats received days 10-13 of pregnancy a new antiviral drug bonaphthon (400 mg/kg) which exerts a toxic effect on females. The progeny did not show postnatal death or reduction of the life span. Moreover, no impairment of muscle work capacity, basal metabolism, cardiovascular system, peripheral blood parameters, or changes in the function of organs and systems were recorded. Morphological and functional deviations in the liver of 2-month-old progeny were unstable and got repaired by 3 months of age.
The toxicity of the original drug bonaphthon was studied in pregnant and nonpregnant mice and rats given the drug orally and intraperitoneally. In a dose of 100 mg/kg bonaphthon had no toxic effect on pregnant rats after 4-time administration per os, while in a single dose of 400 mg/kg the drug elicited side effects such as congestion phenomena and inconsistent dystrophic changes in the parenchymal organs. Toxic effects in the liver were most pronounced when the drug was administered in the earlier periods of pregnancy.