Ferroptosis and 17β-oestradiol

Chris2401

Hey,
I am seeking an explanation or insight into this paper. https://pubmed.ncbi.nlm.nih.gov/37116254/

How can estrogen protect against lipid peroxidation and alleviated ferroptosis? Ray said in his newsletter "Estrogen, iron, degenerative
aging, and progesterone" that high estrogen leads to iron accumulation, which could cause lipid peroxidation.

LucH

@Chris2401 said in Ferroptosis and 17β-oestradiol:

I am seeking an explanation or insight into this paper. https://pubmed.ncbi.nlm.nih.gov/37116254/

Hi,
I Won't trust much pharma when saying taking a supplement of estrogens is beneficial. You know why if you've read RP.
It's going to simulate serotonin and a lot of "depending" processes.

See this link to understand the ferroptosis mechanism, with protective effects.
https://bioenergetic.forum/topic/3374/ferroptosis-and-17β-oestradiol

Chris2401

@LucH Yes i know about the toxic effects of estrogen and further cascades. I was just curious about this and see if i understand things correctly.

In the paper they mention decreased dihydroorotate dehydrogenase expression (after OVX), so estrogen should increase the activity of it. Dihydroorotate dehydrogenase catalyzes ubiquinon to ubiquinol and a reduced pool of ubiquinon is a marker of Reverse Electron Transport (RET). The RET leads to an increased ROS production, which leads, depending on the fatty acid structure (saturated vs. unsaturated) to more lipid peroxidation.

So if i understand this correctly, how on earth should estrogen be helpful in this situation? It should rather be toxic given the above mentioned information.

LucH

@Chris2401

Of what I understand.
They make a supposition.
Ovarian removal operation (OVX) induces a lack of estrogen, like in age-old-years, pretending it induces a decline and a neurodegenerative process.
They make a correlation: iron accumulates with time. Excess iron is creating ROS.
Female rats have showed decreased dihydroorotate dehydrogenase (DHODH) expression when getting under OVX.
However DHODH supports a vital role in neuronal ferroptosis.
But E2 alleviates ferroptosis induced by erastin and ferric ammonium.
So, if we try to link:
a) OVX + neuro-decline + lack of estrogen
b) Excess iron in menopause + lack of estrogen
=> If A induces B, and if C induces B, A should equal C.
If excess iron induces ROS and lipid peroxidation, take the way back and get estrogen to cancel the decreased DHODH induced by ovarian removal operation (OVX).

How does iron cause ferroptosis?
Taken together, excess iron in both the cytosol and mitochondria significantly contributes to the development of ferroptosis in neurodegenerative diseases, and this occurs primarily through its promotion of oxidative stress and lipid peroxidation.

Note1: One correlation seems to give an analogy but not an equivalence. Expressed differently, pharma tries to find positive effect to supplementing E2, event by arranging or inventing improvements.
Note2: Estrogen is not directly linked to ROS. Iron is linked to ROS and ROS induce membrane peroxidation.