Avaliação do potencial da piperina em reduzir os efeitos adversos causados pela doxorrubicina em tecido ovariano de camundongos fêmeas

Abstract

The use of chemotherapy drugs has caused fertility problems in recent years, therefore, natural products emerge as a potential pharmacological factor capable of reducing ovarian damage in vivo. Therefore, this proposal aimed to evaluate the action of piperine (PIP) on ovarian toxicity induced by doxorubicin (DOX) in female mice, using the in vivo model. To this end, this project was submitted to ethical assessment by the CEUA of the Federal University of Ceará, Sobral campus and approved under protocol No 08/21. The following experimental protocol was carried out: the animals received a single dose of DOX and were treated for 10 days orally (gavage) with PIP. The experiment continued based on the evaluation of the following groups (n=6/group): (Group 1) Negative Control (DMSO); (Group 2) Positive Control (NAC (150 mg/kg) + DOX (10 mg/kg); (Group 3) DOX (10 mg/kg); (Group 4) PIP 0.1 + DOX (10 mg/kg ); (Group 5) PIP 1.0 + DOX (10 mg/kg); (Group 6) PIP 10.0 + DOX (10 mg/kg); (Group 7) PIP 0.1; (Group 8) PIP 1.0; (Group 9) PIP 10.0. The ovaries were used for histological and collagen analyses, in addition to biochemical analysis and relative expression by real-time PCR for antioxidant enzymes. The percentages of follicles were evaluated by the chi test -square. Data on collagen fibers and stromal cell density were analyzed using the Kruskal-Wallis test, followed by Dunn's comparison test and p ≤ 0.05 was considered statistically significant. The data obtained suggest that PIP (0.1, 1 and 10 mg/kg) does not have toxic effects on follicles or ovarian tissue in mice and contributes to increasing follicular growth and survival rates in vivo. When administered in combination with DOX (10 mg/kg), PIP (0.1 mg /kg) was able to reduce the deleterious effects on ovarian stromal cells and was able to maintain follicular development. In the biochemical evaluation of antioxidant enzymes, the presence of DOX did not affect negatively, while the presence of PIP protected against damage caused by these drugs. Furthermore, gene expression showed that antioxidant capacity was decisive, showing that PIP (0.1 mg/kg) had better antioxidant capacity against the damage caused by DOX. Given the above, we can conclude that PIP 0.1 mg/kg suggests a protective effect on the ovaries of female mice treated with DOX.