Estradiol and Raloxifene Protect Ovariectomized Mice from Acute Kidney Injury via G Protein-Coupled Estrogen Receptor-Mediated Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Activation.
Level 5 - mechanism / opinion, no new human data
Animal laboratory experiment
PubMed 41977254 · doi:10.3390/ijms27073070
What was done
Female ovariectomized (OVX) mice subjected to renal ischemia-reperfusion injury (IRI) were pretreated for four weeks with estradiol (E2), raloxifene (RAL), RAL plus an Nrf2 inhibitor (ML385), or RAL plus a GPER antagonist (G15). Investigators assessed renal histology, inflammatory markers (IL-1β, IL-6, TNF-α), oxidative stress parameters (MDA, SOD, CAT, GSH), and nuclear Nrf2, GPER, HO-1, and NQO1 expression.
What was found
No numerical values were reported in the abstract. OVX IRI increased IL-1β, IL-6, TNF-α, and MDA, while decreasing SOD, CAT, GSH, and nuclear Nrf2. Pretreatment with E2 or RAL improved renal histology and function, reduced inflammatory and oxidative markers, restored GPER expression, increased nuclear Nrf2, and upregulated HO-1 and NQO1. Co-treatment with either ML385 or G15 reversed RAL's protective effects, reduced nuclear Nrf2, and worsened tissue injury.
Why it matters
This study outlines a mechanistic pathway wherein estrogen receptor modulation mitigates ischemic kidney injury via GPER-dependent Nrf2/HO-1 signaling in an estrogen-deficient model, suggesting potential targets for postmenopausal renal ischemia.
Limits
Sample size was not reported in the abstract, and no quantitative data, effect sizes, or confidence intervals were provided. Findings are restricted to an animal model of acute surgical ischemia-reperfusion and cannot be directly extrapolated to human clinical acute kidney injury.
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