Protective <i>in vitro</i> effects of <i>Aloe vera</i> on doxorubicin-induced ovarian toxicity in mice

The present study investigated the protective effect of <i>Aloe vera</i> extract against the toxic effects of doxorubicin (DOX) on mice ovaries cultured in vitro. Female <i>Swiss</i> mice with regular estrous cycle were used. The animals (n = 48) had their ovaries collected and cultured individually in a 24-well plate at 37.5°C in 5% CO₂ for 6 days. The ovaries were culture DMEM⁺ alone or supplemented with DOX (0.3 μg/ml), as well as both DOX and <i>Aloe vera</i> (5%, 10%, 25%, or 50%). After culture, ovaries were fixed for histological analysis (follicle morphology, growth and activation, extracellular matrix (ECM) configuration and stromal cell density), immunohistochemistry (<i>TNF-α</i> expression) or stored at - 80°C to evaluate the levels of mRNA for superoxide dismutase (<i>SOD</i>), catalase (<i>CAT</i>), nuclear factor-erythroid 2-related factor 2 (<i>NRF2</i>) and tumoral necrosis factor-α (<i>TNF-α</i>) by real-time PCR. The results showed that ovaries cultured with DOX had a lower percentage of normal follicles and reduced stromal cell density, but when <i>Aloe vera</i> extract was added to the culture medium, there was a protective effect on the ovarian structure against the deleterious effects of DOX. In addition, ovaries cultured with both DOX and <i>Aloe vera</i> (10 and 25%) had reduced <i>TNF-α</i> immunostaining and increased expression of mRNA for antioxidant enzymes (<i>SOD</i>, <i>CAT</i>, and <i>NRF2</i>). In conclusion, <i>Aloe vera</i> is associated with a protective effect on ovarian follicles and stromal cells against DOX-induced toxicity. Therefore, <i>Aloe vera</i> has great potential to preserve fertility in patients undergoing chemotherapy treatment, which often cause irreversible damage to oocytes.