Indole-3-carbinol attenuates cisplatin-induced premature ovarian failure by activating Nrf2 through competitive binding of Keap1 - PubMed
3 hours ago
- #Premature ovarian failure
- #Nrf2
- #Ferroptosis
- Indole-3-carbinol (I3C) attenuates cisplatin-induced premature ovarian failure (POF) by activating Nrf2 through competitive binding to Keap1.
- Nrf2 knockout (Nrf2-KO) mice showed decreased levels of Gpx4 and Slac7a11, increased oxidative stress, and fibrosis, similar to cisplatin-induced damage.
- I3C treatment or Nrf2 overexpression reduced cisplatin-induced ferroptosis in vitro, while Nrf2 knockdown or inhibition nullified I3C's protective effects.
- Nrf2-KO mice exhibited POF phenotypes, and I3C's protective effects were lost in these mice.
- I3C activates Nrf2 by competitively binding to Keap1 residues Y334, S363, and R380.
- Nrf2 inhibits ferroptosis by regulating NNT to maintain redox balance; NNT overexpression reversed oxidative damage from Nrf2 loss.
- The study clarifies Nrf2's role in ovarian function and identifies I3C as a potential drug to alleviate ovarian damage.