The abstract is read at the publisher; the summary is JClub's.
Long-term estrogen deprivation in ovariectomized female C57BL/6JOlaHsd mice is linked to sustained NRF2 activation and reduced acetaminophen-induced liver injury after 360 or 600 mg/kg dosing.
- Why it matters: Menopause-associated estrogen decline changes hepatic lipid metabolism, but how it shapes susceptibility to acetaminophen overdose–related injury is unclear.
- What they did: The study combined a multicenter patient cohort after APAP overdose with OVX or sham mice challenged 6 months later, using NRF2 silencing, estradiol replacement, and high-fat diet lipid modulation plus lipidomics and human biopsy validation.
- The result: Women ≥50 years had lower risk of severe AP-ILI, matching OVX mice; estrogen deprivation drove larger lipid droplets and saturated neutral lipid enrichment that enhanced NRF2 signaling and hepatoprotection, reversed by estradiol replacement and supported by higher hepatic NRF2 and target gene expression in women over 50.
The findingWhy it mattersWhat they didThe result
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