Extrato de actaea racemosa (l.) como agente protetor do tecido ovariano de camundongos fêmeas induzidas à quimioterapia com doxorrubicina.

Abstract

In view of the problems caused by chemotherapy drugs in the cancer treatment, its necessary to search for reproductive biotechniques that allow the maintenance of female fertility. Doxorubicin (DOX) is an antineoplastic agent used in medical practice. However, there is evidence of its ability to cause damage to the ovary, opening possibilities for studies of medicinal plants that potentially have a protective effect on follicular development, such as Actaea racemosa L. (AR). Thus, considering the negative effects of DOX on ovarian function, this study aimed to investigate the action of AR extract as a potential factor capable of reducing ovarian damage in vivo. This study was approved by CEUA-UFC under number 01/21. In experiment 1, the action of AR extract (0.5, 5 and 50 mg/kg, p.o.) on the growth and survival of ovarian follicles from female mice treated for 10 days was evaluated. In experiment 2, the protective action of AR (0.5 and 5 mg/kg) in mouse ovaries after induction of chemotherapy with DOX (10 mg/kg) was evaluated. For this, the mice were pretreated with saline solution (control, 0.15 M, p.o.) or with AR (0.5 or 5 mg/kg, p.o.) and received saline solution (control, 0.15 M, i.p.) or DOX (10 mg/kg, i.p.), then treated with saline (control, 0.15 M, i.p.) or AR (0.5 or 5 mg/kg, p.o) once daily for 10 days. The percentages of normal, primordial and developing follicles were evaluated using the chi-square test. Data on collagen fiber distribution and stromal cell density were analyzed using the Kruskal-Wallis test, followed by the Dunn’s comparison test. Data were defined as the mean and standard error of the mean (mean±SE) and p ≤ 0.05 was considered statistically significant. The obtained data suggest that the AR extract (0.5, 5 and 50 mg/kg) has no toxic effects on follicles or ovarian tissue in mice and contributes to increasing follicular growth and survival rates in vivo. When administered associated with DOX (10 mg/kg), AR (0.5 and 5 mg/kg) was able to decrease apoptosis in ovarian stromal cells. AR (0.5 mg/kg) was also able to maintain the ultrastructure of granulosa cells and oocytes from preantral ovarian follicles. There was a greater immunostaining pattern for TNF-α in DOX (10 mg/kg), while AR (0.5 mg/kg) stained moderately. Investigations on the ability of natural products, such as AR derivatives, to mitigate the adverse effects caused by DOX, may contribute to the identification of a new therapeutic approach for the preservation of fertility in the face of chemotherapy treatments.