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. Combined administration of paclitaxel and p-tyrosol alleviated the delayed effects of the cytostatic treatment on the prepubertal testis.

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. These changes were accompanied by a decrease in the level of free radicals, an increase in antioxidant protection, and normalization of the redox potential.

Reproductive Toxicity of Theobroma cacao: Increase in Survival Index, Nongenotoxic, and Proimplantation Potential.

Unsweetened natural cocoa (UNCP) was evaluated for reproductive toxicity in rats. A preliminary genotoxic potential was evaluated by the DNA comet assay test using C57Bl/6 mice. Both therapeutic dose (TD; 900 mg/kg) and high dose (HD; 9000 mg/kg) of UNCP were used. White Wistar rats were used in two experimental groups. The females received UNCP 15 days before crossing with untreated males. The males received UNCP for 48 days before mating with untreated females. Subacute toxicity was observed during a 14-day oral administration of UNCP. Results show that a high tail DNA% was observed with methyl mesylate administration in all tissues analysed. The lowest tail DNA% value was observed in the liver (1.64 ± 0.26) and kidney (1.63 ± 0.30) during UNCP (TD) administration. UNCP did not induce observable physical congenital malformations on the pubs of treated female and male rats, lacks genotoxic potential, and did not adversely affect pregnancy index, pub weights, and survival index, but UNCP exhibited proimplantation potential (p > 0.05).

Effectiveness of Phenolic Antioxidants in Experimental Model of Benign Prostatic Hyperplasia.

Experimental model of sulpiride-provoked benign prostatic hyperplasia was employed to comparatively assess the effect of phenolic antioxidants (dihydroquercetin, p-thyrozol, dibornol, and prostagenin) on prostate morphology. All examined agents decreased the degree of hyperplasia in acinar epithelium; the greatest efficacy was demonstrated by prostagenin. Moreover, dihydroquercetin and p-thyrozol increased the cross-section area of acinar lumina and prostate volume, which is inadmissible in this pathology. These results suggest that the use of phenolic antioxidants in the therapy of benign prostatic hyperplasia should be strictly controlled.

Evaluation of Kagocel Genotoxicity.

Antiviral drug Kagocel in concentrations of 0.0008, 0.004, 0.02, 0.1, 0.5, and 2.5 mg/ml with or without metabolic activation does not induce gene mutations in S. typhimurium strains ТА98, ТА100, ТА1535, and ТА1537 and in a combination of E. coli strains pKM101 and uvrA. A single intragastric administration of Kagocel in a daily therapeutic dose and a 10-fold daily therapeutic dose to male mice or multiple administrations in daily therapeutic dose to male and female mice did not led to a significant increase in the percentage of chromosomal aberrations in the bone marrow cells. DNA comet assay revealed no significant increase in the incidence of DNA breaks in cells of mouse testes after single or multiple administration of Kagocel at daily therapeutic and 10-fold daily therapeutic doses. Our results indicate that Kagocel exhibits no genotoxic activity in the studied dose range.

Experimental Study of the Effectiveness of Phenolic Antioxidants in Male Infertility Caused by Pathospermia.

The effect of phenolic antioxidants (dihydroquercetin, p-tyrosol, dibornol) on the morphology, functions, and redox processes in the reproductive cells of male rats was studied on the model of experimental pathospermia. All antioxidants reduced the percentage of degenerative forms of spermatozoa. Dibornol was most effective. Dihydroquercetin and p-tyrosol did not increase the total number of spermatozoa and the percentage of their mobile forms. These indicators were improved only by dibornol. After administration of all test drugs, the antioxidant potential of spermatozoa increased and did not significantly differ from the baseline values.

Experimental Analysis of the Efficacy of Dihydroquercetin on the Model of Chronic Nonbacterial Inflammation of the Prostatic Gland.

We studied the efficiency of dihydroquercetin on the model of chronic nonbacterial inflammation of the prostatic gland in rats. It was found that administration of dihydroquercetin was followed by a significant decrease in the area of the connective tissue in the prostatic gland to initial levels, which attested to antifibrotic properties of this oxidant. Additionally, the substance prevented the development of atrophy of acinus epithelium. After administration of reference drug Prostamol Uno, only moderate antifibrotic effects were observed.

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. Effectiveness of the immobilized form of the drug was superior to that of non-immobilized form.

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.

Simulation of category IIIB prostatitis.

Blood flow arrest in the inferior vena cava at the level of the inferior pole of the kidney led to the development of epithelial degeneration and stromal sclerosis after 1.5 months, dilatation of the veins, and congestion of secretion in rats. These signs corresponded to the morphological picture of category IIIB prostatitis or to signs of noninflammatory chronic prostatitis (hemodynamic disorders, sclerosis, degeneration). On the other hand, there was no cellular infiltration of the glandular tissue associated with infection and inflammation.