Liu · Journal of biochemical and molecular toxicology 2025 · Comparative in vitro and in vivo animal laboratory study · n=?

Comparison of Antioxidant Effects of 3-Hydroxybutyrate and Sodium 3-Hydroxybutyrate Through SIRT3/FOXO3A Pathway: Implications for In Vitro and In Vivo Research.

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Level 5 - mechanism / opinion, no new human data

Bench (in vitro cell culture) and animal laboratory research

PubMed 40965455 · doi:10.1002/jbt.70502 · record verified 2026-08-29

What was done

The authors compared the antioxidant effects of 3-hydroxybutyrate (3HBH) and sodium 3-hydroxybutyrate (3HBNa). In vitro, H2O2-treated BV2 microglial cells were assessed for viability (CCK8), total glutathione (T-GSH), malondialdehyde (MDA), reactive oxygen species (ROS), and apoptosis by flow cytometry. Expression of BCL-2, BAX, CASPASE-3, SIRT3, and FOXO3A was quantified using RT-qPCR and Western blot. In vivo, blood ketone concentrations were measured at multiple time points in mice administered equivalent doses of 3HBH or 3HBNa.

What was found

The abstract reports no numeric values, effect sizes, or exact p-values. Qualitatively, both 3HBH and 3HBNa exhibited antioxidant and anti-apoptotic effects in H2O2-treated BV2 cells, with 3HBH showing stronger efficacy and greater activation of the SIRT3/FOXO3A pathway than 3HBNa. In vivo, blood ketone levels showed no significant difference between mice receiving 3HBH versus 3HBNa.

Why it matters

Preclinical studies frequently treat the acid and sodium salt forms of beta-hydroxybutyrate as interchangeable; these findings indicate formulation-dependent potency differences in cell culture models despite similar systemic ketone elevations in mice.

Limits

The abstract provides no sample sizes (animal count or cell culture replicates), drug dosages, or quantitative statistical data. Findings in cultured BV2 mouse microglia and normal mice cannot be directly extrapolated to human clinical outcomes.

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