Estrogen loss reduced acetaminophen liver injury in mice
Female mice given acetaminophen six months after ovary removal showed altered liver fats and sustained activity of a stress-defense protein.
Our read
Mechanisms- Studied:
- Preprint: experiments in female C57BL/6JOlaHsd mice, six months, against sham-operated mice (Multicenter)
- What changed:
- Mice with long-term estrogen loss were less susceptible to acetaminophen liver injury than sham-operated mice
- The catch:
- Only overdose challenges were used, at 360 or 600 mg/kg acetaminophen
- In the record:
- One of 296 papers on high-fat diet on record: 15 with results in people, 149 in animals.
Editor of record: Boris Djordjevic · AgingResearch.News
Female C57BL/6JOlaHsd mice underwent removal of both ovaries or sham surgery at 12 weeks of age in an experiment modeling long-term estrogen deprivation. Six months later, they received acetaminophen at 360 or 600 milligrams per kilogram of body weight.
Mice with long-term estrogen loss were less susceptible to liver injury. Their livers developed larger fat droplets and changes in fat composition. These changes promoted sustained activation of NRF2, a protein that turns on stress-defense genes. A high-fat diet strengthened the fat changes, NRF2 signaling and liver protection. Replacing estradiol, a form of estrogen, reversed these effects. The authors concluded that liver fat remodeling protected against acetaminophen injury by sustaining NRF2 activity.
Why it matters
Estrogen decline at menopause raises questions about how the liver’s response to drug stress changes with age.
Caveats
The mouse experiments cannot show that estrogen loss protects women from acetaminophen injury through the same mechanism. This preprint has not been peer-reviewed.
Where the evidence stands
High-fat diet
- 180 independent labs in 42 countries
- 22 findings against
- Funders: National Institutes of Health and others
- 14 of 542 findings with company ties
Estradiol
- 232 independent labs in 39 countries
- 52 findings against
- 178 trials, 59 with no results posted
- Funders: National Institutes of Health and others
- 38 of 716 findings with company ties
- 24 of 178 trials sponsored by its developers
The paper
Centro de Biologia Molecular Severo Ochoa (CSIC-Universidad Autonoma de Madrid)
bioRxiv, Nov 12, 2026, Open access, Preprint, not yet peer-reviewed
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