Preclinical studied of general toxic properties of preparations containing ultralow doses of antibodies to endogenous regulators.

Preclinical study of the safety of 6 preparations containing ultralow doses of antibodies to endogenous regulators showed that they are relatively safe, are well tolerated by animals in doses more than 1000-fold surpassing the therapeutic dose for humans, and produce no general toxic effect on the organism of laboratory animals.

[Influence of taxan-containing cytostatic preparations on the progeny].

In experiments designed to study effect of taxan-containing agents on the progeny of Wistar rats, one of the parents was given a single intravenous injection of the antineoplastic drug paclitaxel 1, 3 and 6 months before crossing with the untreated partner. The number of systemic pathological changes in the off-springs of paclitaxel-treated females was significantly greater and their spectrum wider than in those of the treated males. Severity of toxic effects depended on the time of crossing after drug administration.

The rat spermatogenesis after injection of paclitaxel (antitumor agent).

Morphological and functional characteristics of spermatogenesis in rats were studied during the early and delayed periods after single injection of paclitaxel (antitumor agent) in the maximum tolerated dose. The drug induced structural changes in the gonads associated with oligospermia and increased number of pathological forms of spermatozoa with reduced functional activity.

[Experimental study of the mechanisms of the tissue repair activity of complex and individual agents isolated from Delphinium elatum].

It is demonstrated in experiment that the entire complex and individual agents isolated from the above-ground part of bee larkspur Delphinium elatum stimulate the reparative regeneration of skin in white mongrel mice. The maximum activity was exhibited by the alkaloid fraction of Delphinium elatum.

Immune reactions in the progeny of female rats treated with paclitaxel.

Immune reactions of the progeny of female Wistar rats injected with paclitaxel a single MPD of 1 and 3 months before mating with intact males were studied. Thymic hyperplasia was detected in the progeny of female rats mated 1 month after treatment. Disorders in the antibody-specific and antibody-nonspecific mechanisms of the immune response were detected in the progeny of females mated with intact males 3 months after cytostatic treatment.

The stage of offspring of female rats after treatment with cytostatics of various groups.

We examined the offspring of female rats that were mated with intact males in the delayed period after administration of cytostatic drugs Farmorubicin, platidiam, carboplatin, etoposide, and paclitaxel (1, 3, and 6 months post-treatment). Toxicity of these drugs in the offspring decreased in the following order: paclitaxel > etoposide > carboplatin > platidiam > Farmorubicin. The toxic effect depended not only on the type of cytostatic treatment, but also on the period of conception.

Pharmacological correction of etoposide ovariotoxicity.

The possibility of reducing the ovariotoxicity of antitumor drug etoposide with buserelin, a hypothalamic regulator of pituitary function, was studied in female Wistar rats. Quantitative analysis of ovarian structural and functional elements on serial sections through the entire organ showed that 3 months after combined treatment with etoposide and buserelin, the morphological picture of the ovarian glands did not differ from that in intact animals of the same age, while etoposide monotherapy led to earlier development of atrophic processes. Six months after treatment, the number of bi- and multilayer follicles was significantly higher in rats receiving combined therapy compared to animals treated with etoposide alone.

[Myelotoxicity of paclitaxel (mitotax)].

Paclitaxel (single intravenous injection in a maximum tolerated dose of 4.6 mg/kg) to white outbred rats causes bone marrow hypoplasia, increased granulocyte and erythroid cell mitosis (metaphase-anaphase transition), and moderate pancytopenia developments in peripheral blood (hypoplastic anemia, deep, short-term neutropenia, lymphopenia and thrombocytopenia) in the first hours after injection. A considerable increase of polyploidy (4n) cells and a moderate increase in the structural changes (chromatid deletions) of chromosomes was observed on bone marrow metaphase plates in 24 h.

Morphological and functional state of rat ovaries in the early and late periods after injection of vepesid.

Morphological and functional state of the ovaries in female Wistar rats was assessed in the early and late periods after administration of antitumor drug vepesid in a single maximum tolerated dose. In the early period, the drug pronouncedly decreased the number of primordial follicles, bi- and multilayer follicles, and the total number of generative elements. The number of graafian vesicles and corpora lutea did not decrease.

Evaluation of the progeny of rats treated with topoisomerase II inhibitor vepesid.

Progeny of Wistar rats treated with vepesid 1, 3, and 6 months before mating is characterized by common pathological changes. These changes were more pronounced and more diverse in animals descending from females receiving the cytostatic compared to the progeny of treated males. The severity of toxic effects depended on the period between mating and vepesid treatment.

[Subunits of human holoenzyme of DNA dependent RNA polymerase III phosphorylated in vivo].

Phosphorylation of human holoenzyme of DNA dependent RNA polymerase III subunits in vivo has been investigated. RNA polymerase III from human placenta nuclei and epidermoid carcinoma cells A431 was isolated as two subfractions (IIIa and IIIb) distinguished in the order of elution from DEAE Sephadex A-25 column chromatography and buoyant density at glycerol gradient centrifugation. The subfractions of RNA polymerase III holoenzyme consists of four subunits with molecular masses 60, 52, 45 and 38 kDa, respectively, phosphorylated in vivo.

Effect of vepeside on the function of reproductive system in rats.

Experiments on adult rats showed that a single intravenous injection of antitumor drug vepeside in a MTD (maximum tolerable dose) reduced the reproductive status during periods corresponding to exposure of mature sex cells, spermatocytes, and spermatogonia in male rats and exposure of oocytes in ovulating, mature, and primordial follicles in female rats. Reduction of the male and female reproductive function manifested in increased antenatal mortality of the progeny. The toxic effects of the drug on mature male sex cells caused temporary partial infertility.

Stress-inducing effect of hypoxia of different origin and its correction with Inula Helenium L. tincture.

In order to evaluate the severity of stress, the effects of single and repeated exposure to hypoxia of different origin (hemic, tissue, and circulatory) on the classical parameters of the Selye triad, cytological characteristics of lymphoid organs, and karyometric parameters (nucleus diameters) were studied in all adrenal zones, and analysis of correlations was carried out. The corrective effect of Inula helenium L. tincture manifested in prolongation of the life-span and normalization of somatic and morphological parameters.