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

3-hydroxybutyrate (3HBH) and sodium 3HBH (3HBNa) have been used in many studies, leading to confusion about their roles. The present study aimed to compare the antioxidant effects of 3HBH and 3HBNa. The CCK8 was used to assess the antioxidant effect of 3HBH and 3HBNa on H₂O₂-induced BV2 cells. Total-glutathione (T-GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were measured. Apoptosis was evaluated by flow cytometry. Western blot and RT-qPCR were used to detect the protein and mRNA expression levels of BCL-2, BAX, CASPASE-3, SIRT3, and FOXO3A. Blood ketone concentrations of the mice were recorded at different time points after administration of the same dose of 3HBNa and 3HBH. Both 3HBH and 3HBNa showed anti-oxidative and anti-apoptotic ability on H₂O₂-induced BV2 cells, but the ability of 3HBH was stronger than that of 3HBNa. 3HBH exhibited a stronger ability to activate the sirtuin 3 (SIRT3)/forkhead box O3 (FOXO3A) pathway. The ability of ketogenic effects was no significant difference between 3HBH and 3HBNa in in vivo studies. These findings suggest prioritizing 3HBH over 3HBNa in in vitro research. However, both options are available in in vivo studies from a ketogenic perspective.