[Effect of the platinum-containing cytostatics on the rat offspring].
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Biomedical subjects
Publications and source records attributed to T G Borovskaia.
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The effect of doxorubicin, an anthracycline antibiotic, on the reproductive system and progeny was studied in rats 1 month after a single administration of the drug in the MID of 6.85 mg/kg. It was shown that doxorubicin induced a decrease in the number of the mature oocytes in the rat ovary and an increase in the pre- and post-implantation death rate. The rats exposed to the antibiotic 1 month before the mating with intact male rats had unchanged fertility and pregnancy. In the fetuses isolated from the female rats treated with the antibiotic, development of some parts of the skeleton appeared to be retarded. One fetus and one young rat had severe developmental anomalies in the skeletons: shorter right anterior and hind extremities and finger aplasia. The survival rate of the progeny from the female rats exposed to the antibiotic was markedly decreased. No retardation in the physical development of the progeny was observed.
The advancement of Pliss' lymphosarcoma in rats was shown to be associated with disorders of platelet-mediated hemostasis presenting with either lowered or increased aggregation activity of platelets. In the latter case, a direct correlation was observed between functional activity of thrombocytes, on the one hand, and degree of tumor advancement and its metastatic activity, on the other. Extract of Scutellaria baicalensis Georgi was shown to produce a normalizing effect on platelet-mediated hemostasis whatever the pattern of alteration which points to the adaptogenic activity of the drug. This activity is thought to be responsible for the drug's antitumor and, particularly, metastasis-preventing effect.
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The study was concerned with an attempt at reducing the acute toxic effect of 5-fluorouracil (5-FU) on gut mucosa in mice with Ehrlich ascites tumors. An official preparation of plantain sap was shown to ward off this effect and to contribute to the normalising of certain parameters of epithelial cells. The DNA level of tumor cells showed a more drastic decline after combined treatment with 5-FU and the preparation than after the cytostatic drug alone.
A new drug preparation ecorsin based on the dry aspen bark extract was studied for toxicological safety on a preclinical stage. The drug exhibited no toxicity upon a single administration to rats and mice (both male and female). The intragastric administration of ecorsin for 3 months to rats (at a daily dose of 50, 250, and 500 mg/kg) and rabbits (25 and 50 mg/kg) led to neither functional not morphological changes in hemopoietic and lymphoid organs, liver, kidney, heart, digestive system, and CNS. The long-term administration resulted in a partial atrophic modification of convoluted seminiferous tubules in impuberal male rats, while not affecting the testes of aged animals. The administration of ecorsin at 50, 250, and 500 mg/kg led to dose-dependent changes in some characteristics of the reproductive capacity in rats. Ecorsin did not modify the extent of allergic reactions and produced no immunotoxicant and mutagen effects.
A new D-glucuronic acid (DGA) preparation was studied for toxicological safety on a preclinical level. The results obtained upon a single acute DGA administration in rats, mice, and rabbis showed that the drug exhibits moderate toxicity. A one-month treatment of rats (at a single daily dose of 50, 250, and 500 mg/kg, i.p.) and dogs (50 mg/kg, i.v.) induced neither functional nor morphological changes in hemopoietic and lymphoid organs, kidney, heart, as well as in the digestive, nervous, hemostatic, and fibrinolytic systems. The intraperitoneal administration of DGA produced a pronounced local irritation effects. The liver of both rats and dogs treated with DGA showed dose-dependent adipose degeneration, which decreased upon the drug abolition. The administration of DGA in 50, 100, and 250 mg/kg doses led to dose-dependent changes in some characteristics of the reproductive system in rats. DGA did not modify the extent of allergic reactions and showed no immunotoxicant and mutagen properties.
The safety of bayacon, a new drug based on Baikal aconite intended for the treatment of inflammation-proliferative dermatitis (psoriasis), was studied on a preclinical level. With respect to a single introduction in rats and mice, the drug is classified as a low-toxicity substance. However, a 3-month oral administration of bayacon (0.25, 0.5, and 2.5 mg/kg) in rats showed a number of dose-dependent functional and morphological changes. A dose of 2.5 mg/kg induced weak hyporegenerative anemia, neutrophile leukocytosis, and dystrophic changes in the stomach mucosa, heart, liver, and kidneys. All these symptoms disappeared within two weeks after abolition of the drug. Oral administration of bayacon (0.1 and 0.5 mg/kg) in rabbits produced no pathological morphofunctional changes in the organs and tissues studied. In rats, bayacon 2.5, 0.5, and 0.25 mg/kg doses of bayacon led to dose-dependent changes in some characteristics of the reproduction system. The drug did not influence the expression of allergic reactions and showed no immunotoxicity and mutagenicity manifestations.
Pregnant rats exhibited regenerative anemia development 3 months upon a single intravenous injection of carboplatin in a maximum tolerated dose; the effect increased by the end of pregnancy. The character of changes in parameters of the peripheral and central erythron parts (increased level of erythrocyte hemolysis, decrease in the amount of erythrocytes, increase in the number of reticulocytes, development of erythropoietic hyperplasia in bone marrow and spleen) was indicative of the hemolytic type of anemia.
The experiments performed on Wistar rats showed morphological damages of the rat testis over a one-month period after platidiam administration (4 mg/kg, one-time intravenous injection), namely a decrease in the index of spermatogenesis, in the number of normal spermatogonia, Leydig cells, and testis tubes at the 12th stage of meiosis and an increase in the number of testis tubes squamous epithelium. In the remote period (3 and 6 month after platidiam administration) the recovery of morphological and functional state of the rat testis was observed.
Experiments on Wistar rats studied the state of the posterity born as a result of mating of intact females with males, who were injected with the antitumor drug platidiam one month before mating (once, intravenously, maximal tolerance dose). The pre- and postimplantation death rate did not grow in female rats mated with test males. However, the fetuses showed visceral anomalies and delayed development of skeleton. A decrease in the muscle tone, as well as ability for the training and extrapolation behavior, were observed in some newborn rat pups.
Experiments were performed on Wistar rats to evaluate comparatively the morphological and functional state of the ovaries in the early and late-term periods after a single injection of a platinum-containing cytostatic drug platidiam and an antibiotic of the anthracycline series farmorubicin. It was found that the antineoplastic agents caused a similar toxic effect on the animal's sexual glands. The number of generative elements in the ovaries decreased in this case and the duration of the estrous cycle, the indices of embryonal death, and the pregnancy index increased.