Regenerative Potential of Granulocyte Colony-Stimulating Factor Immobilized by Using Electron-Beam Synthesis Nanotechnology in an Experimental Model of Ovarian Reserve Depletion.

The pharmacological activity of granulocyte CSF (G-CSF) immobilized using electron-beam synthesis nanotechnology (imG-CSF) was evaluated in an experimental model of ovarian reserve depletion. The effectiveness of the drug was compared with that of its unmodified form. Depletion of the ovarian follicular pool in female Sprague-Dawley rats was caused by a single intravenous injection of the antitumor drug etoposide in the maximum tolerated dose.

Assessment of Ante- and Postnatal Development of the Offspring of Male Rats Crossed in Delayed Periods after Treatment with Methotrexate in Low Doses.

We studied ante- and postnatal development of the offspring of intact female rats crossed with males injected with low doses of methotrexate 3 and 6 months before mating. The time of crossing corresponded to the manifestation of the cytostatic effect on spermatogonial stem cells. The offspring of methotrexate-treated males was characterized by increased preimplantation losses and fetal growth restriction in the antenatal period and inhibition of physical development, delayed formation of sensory-motor reflexes, and impaired learning abilities in the postnatal period.

Experimental Evaluation of the Effectiveness of Isobornylphenols in the Model of Pathospermia and Their Effect on the Antioxidant-Prooxidant Balance of Male Germ Cells.

We studied the effect of antioxidants dibornol (2,6-diisobornyl-4-methylphenol) and its derivative (4-hydroxymethyl-2,6-diisobornylphenol), members of the alkylated phenols group, on the redox potential of male germ cells and their morphological and functional state in the rat model of pathospermia. Pharmacological effect was observed in animals treated with dibornol. The studied compounds led to the normalization of the antioxidant-prooxidant balance.

Delayed Consequences of the Toxic Effect of Paclitaxel on the Testes of Prepubertal Rats and Their Correction with p-Tyrosol.

Delayed gonadotoxic effects were revealed in outbred male sexually mature rats (SD) after exposure to paclitaxel in the prepubertal period, and the possibility of their correction with p-tyrosol was shown. It was found, that administration of paclitaxel does not inhibit the ability of animals to conceive, but impairs the reserve capacity of the testicular tissue. In intact female rats crossed with male rats receiving paclitaxel, increased post-implantation fetal death was observed.

Estimation of the Regenerative Potential of para-Tyrosol in the Model of Testicular Insufficiency Caused by Damage to Spermatogonial Stem Cells.

The regenerative properties of p-tyrosol were investigated in a model of testicular insufficiency caused by a toxic effect on spermatogonial stem cells (single administration of paclitaxel in the maximum tolerable dose). Against the background of p-tyrosol administration, we observed an increase in the number of normal spermatogonia and Sertoli cells, stimulation of spermatogenesis, and renewal of the spermatogenic tissue. The treatment with p-tyrosol also led to a decrease in DNA damage in cells of the testicular tissue.

Experimental Evaluation of Long-Term Toxic Effects of Methotrexate on Male Reproductive System.

The morphological and functional state of the reproductive system was studied in male outbred rats (SD stock) and male F1(CBA×C57BL/6) mice after long-term (3 months) methotrexate administration. The drug was administered subcutaneously once a week for 4 weeks, the dose for male rats was 1 mg/kg, for male mice 2.2 mg/kg.

Experimental Assessment of the Effect of Kagocel on Reproductive Function in Pubertal Male Rats.

We studied possible toxic effects of antiviral drug Kagocel on reproductive function in pubertal male rats. The drug was administered in therapeutic and 10-fold higher doses throughout the spermatogenesis cycle (48 days). Kagocel did not reduce mating and fertilizing capacities, did not suppress spermatogenesis, and had no toxic effects on the offspring.

Effect of Granulocyte Colony-Stimulating Factor Immobilized by the Electron-Beam Synthesis Nanotechnology on Reparative Regeneration of Spermatogenous Tissue.

Effectiveness of the granulocyte colony-stimulating factor immobilized by using electronbeam synthesis nanotechnology was investigated on the model of experimental testicular failure caused by the toxic effect on stem spermatogonia. Administration of the drug to experimental paclitaxel-treated animals increased the number of sources of the proliferative pool of spermatogenesis and its productivity. The effectiveness of immobilized granulocyte colony-stimulating factor was based on its ability to stimulate reparative regeneration of the spermatogenic tissue, which manifested in a decrease in spermatogenic layer maturity and increase in the number of microenvironment cells.

Dihydroquercetin effects on the morphology and antioxidant/prooxidant balance of the prostate in rats with sulpiride-induced benign hyperplasia.

A course of dihydroquercetin (antioxidant) injections to 5-month-old Wistar rats with sulpiride-induced benign prostatic hyperplasia led to reduction of proliferative activity in the glandular structures and to attenuation of the inflammatory reaction in the tissue. Prostatic antioxidant/prooxidant balance returned to normal after the treatment.

Pharmacological stimulation of the regenerative capacity of rat testes damaged by paclitaxel.

Productivity of spermatogenesis and the population of spermatogonial cells were substantially reduced in male Wistar rats 3 months after administration of cytostatic drug paclitaxel, damaging stem spermatogonia. However, signs of reparative regeneration appeared in the testicular tissue. In animals receiving paclitaxel in combination with granulocyte CSF, the same period of observation, the number of spermatogonia and the efficiency of spermatogenesis at the same terms of the study did not differ from those in intact animals.

Mechanisms of reparative regeneration of rat testis after injection of paclitaxel.

Population of spermatogonia was reduced in 2, 3, and 6 months after single intravenous injection of antitumor drug paclitaxel in maximum tolerated dose (MTD). The count of Sertoli cell increased in 3 months after the start of the experiment. The maturity of the seminiferous tubule epithelium was lower than in intact rats.

Comparative evaluation of the efficiency of prostatotropic agents of natural origin in experimental benign prostatic hyperplasia.

Comparative evaluation of the efficiency of prostatotropic agents was carried out in rat experiments. Serenoa repens plant preparation and polypeptides isolated from the cattle prostate were used for the treatment of benign hyperplasia. Drugs in parallel with sulpiride similarly led to shrinkage of the acinar epithelial area and to emergence of a trend to an increase of the stromal/epithelial proportion, more so after Serenoa repens treatment.

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.

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.

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.