Protective in vitro effects of Aloe vera on doxorubicin-induced ovarian toxicity in mice

Abstract

The present study investigated the protective effect of Aloe vera extract against the toxic effects of doxorubicin (DOX) on mice ovaries cultured in vitro. Female Swiss 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 Aloe vera (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 (TNF-α expression) or stored at - 80°C to evaluate the levels of mRNA for superoxide dismutase (SOD), catalase (CAT), nuclear factor-erythroid 2-related factor 2 (NRF2) and tumoral necrosis factor-α (TNF-α) 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 Aloe vera 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 Aloe vera (10 and 25%) had reduced TNF-α immunostaining and increased expression of mRNA for antioxidant enzymes (SOD, CAT, and NRF2). In conclusion, Aloe vera is associated with a protective effect on ovarian follicles and stromal cells against DOX-induced toxicity. Therefore, Aloe vera has great potential to preserve fertility in patients undergoing chemotherapy treatment, which often cause irreversible damage to oocytes.

Keywords: Aloe vera; doxorubicin; fertility preservation; in vitro culture; mice.