Table 4.
Modulators of NRF2 in ovarian preservation.
| Protector Compound |
Harmful Agent | Mode Studied |
Effect | Ref. |
|---|---|---|---|---|
| SB216763 (GSK-3 inhibitor) |
Doxorubicin (DOX) | Mice | SB216763 and DOX combined treatment enhances NRF2 expression restoring GSH-Px and SOD-1 levels. SB216763 increases primordial, primary, preantral and antral follicles number while decreases atretic follicles number. SB216763 and DOX coadministration reduces the mature oocyte abnormalities. |
[91] |
| Resveratrol (RES) | Busulfan and Cyclophosphamide (Bu/Cy) | Mice | RES activates NRF2 and relieves oogonial stem cells loss attenuating the Bu/Cy-induced oxidative apoptosis in mouse ovaries. | [101] |
| Melatonin | ROS due to cryopreservation | Rat ovarian tissues | Melatonin increases GSH-Px, GSH, CAT and SOD activities in cryopreserved ovarian tissues by activating NRF2 downstream genes HO-1, GSTM1, SOD, and CAT. | [103] |
| Epigallocatechin gallate (EGCG) Theaflavins (TFs) | Cyclophosphamide (CTX) | Mice | Mice exposed to CTX and treated with EGCG and TFs improve ovarian endocrine function and reproductivity reducing the oxidation-induced follicular DNA damage by activating the NRF2/HO-1 and SOD2 pathways and reducing the apoptosis of growing follicles. | [105] |
| Vitamin C | 1-BromoPropane (1-BP) | OVCAR-3 cells | 1-BP treatment leads to increased ROS and MDA production and decreased SOD activity. Vitamin C alleviates 1-BP-induced apoptosis activating NRF2 pathway. | [108] |
| — | Cigarette Smoke Extract (CSE) | SKOV3 and OVCAR3 cells | CSE reduces cell proliferation by Cyclins B1 and decreases D1 expression, and induces apoptosis. CSE induces oxidative stress increasing ROS levels and repressing NRF2 expression by increasing KEAP1. | [110] |