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.

Evaluation of the Effect of p-Tyrosol on the Level of DNA Damage in the DNA Comet Assay In Vivo.

The effect of p-tyrosol on the spontaneous level of DNA damage in the cells of the bone marrow, liver, kidney, and rectum of mice (series I) and on the genotoxic effects of cytostatic drugs with different mechanisms of action in rat testicular cells (series II) was studied by DNA comet assay on C57BL/6 mice. p-Tyrosol was administered in a dose of 40 mg/kg once (series I) or for 5 days before and 5 days after cytostatic exposure (busulfan, paclitaxel, methotrexate; series II). It was found that p-tyrosol reduced spontaneous level of DNA damage in all studied organs.

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.