Experimental Evaluation of Long-Term Adverse Side Effects of Cytostatic Drugs on Female Reproductive Function and Pharmacological Ways to Reduce Them

Abstract

The purpose of the study was a comparative experimental assessment of long-term toxic effects of cytostatic drugs (epirubicin, etoposide, platidiam, carboplatin, paclitaxel) on the female reproductive function and search for pharmacological ways to reduce them.Material and Methods. Experiments were carried out on 200 outbred male rats, Wistar stock, 2.5 months old. Antitumor drugs were administered once, intravenously, in maximum tolerated dose. The reproductive status in rats was assessed 90 and 180 days after injection of cytostatic drugs. Correction of ovariotoxicity of cytostatic drugs was carried out using a recombinant human granulocyte colony stimulating factor (rhG-CS F, Neupomax, FARMSTA NDA RT-UfaVITA OJSC , Russia) and liquid extract of Scutellaria Baikalsky («GNTsLS », Kharkov). The mating and fertility ability of female rats as well as pre- and post-implantation fetal mortality were determined. Ovarian reserve was evaluated using morphological analysis of the ovaries using quantitative assessments of structural damage. Concentration of anti-Muller hormone in the blood of adult rats-females receiving etoposide and rhG-CS F were evaluated by enzyme immunoassay (IFA, ELISA , Cloud clone, Corp. Wuhan). Statistical processing of obtained experimental data was performed using Mann-Whitney U-test and Fisher angular transformation.Results. The mating and fertility ability of animals was found to be persisted. However, signs of early depletion of the ovarian reserve and a decrease in reproductive potential were observed. The risk of early menopause was increased to a greater extent after using epirubicin, etoposide and paclitaxel, and to a lesser extent after platidiam and carboplatin. The reproductive potential of animals was reduced due to increased fetal death. Platinum-containing drugs were found to be the most toxic. G-CS F was the effective drug for protecting the ovarian reserve from cytostatic effects. The use of Scutellaria baicalensis extract increased the reproductive potential of animals by reducing the rate of embryonic death.