Table 2.

Preclinical Evidence for the Antioxidative Stress Effects of KBs and SCFAs

Method of Increasing or Delivering KBs or SCFAs	Experimental Model	Results	Proposed Mechanism
Administration of β-HB via intraperitoneal osmotic pump	Mice model of oxidative stress using IV injection of paraquat, a toxic herbicide that induces oxidative stress and generates ROS in several tissues	Administration of β-HB protected against paraquat-induced oxidative stress and ROS production.	Inhibition of class I HDACs with resultant up-regulation of genes involved in protection from oxidative stress, including FOXO3A and MT2	Shimazu et al61
Treatment of incubated cardiomyocytes with β-HB	Stimulation of cardiomyocytes using H2O2 to induce oxidative stress and generation of ROS	β-HB decreased production of ROS and prevented oxidative stress–induced apoptosis of H2O2-treated cardiomyocytes.	Up-regulation of FOXO3A rescued the decreased levels of the antioxidant enzymes SOD2 and catalase in H2O2-treated cardiomyocytes.	Nagao et al86
IV administration of sodium butyrate (500 mg/kg) to rats 6 h prior to exposure to contrast	Rat model of contrast-induced acute kidney injury using IV administration of metaglumine diatrizoate sodium (6 mL/kg)	Butyrate decreased levels of lipid peroxidation, IL-6, and renal tubular damage.	Butyrate prevented nuclear translocation of NF-κB and thereby decreased subsequent oxidative damage.	Machado et al87
Diet supplemented with 1% sodium butyrate for 10 wk	ApoE−/− mouse model of atherosclerosis and analysis of atherosclerotic lesions in the aorta.	Butyrate decreased area of atherosclerotic lesions in the aorta and decreased oxidative stress in atherosclerotic lesions.	Butyrate resulted in down-regulation of NADPH oxidase in endothelial cells and decreased release of ROS and iNOS from ox-LDL-stimulated macrophages.	Aguilar et al89
Diet containing sodium butyrate at 5 g/kg/d for 20 wk	Streptozotocin-induced diabetes in WT and Nrf2−/− mice	Butyrate attenuated aortic endothelial oxidative stress in WT but not Nrf2−/− mice.	Inhibition of HDAC by butyrate up-regulated the expression of the transcription factor Nrf2, which in turn promoted expression of antioxidant enzymes.	Wu et al90
Acetate or butyrate administered in drinking water at 100 mmol/L and 0.5 mg/kg/d, respectively	SHRs as a genetic model of hypertension	Acetate or butyrate reduced blood pressure and decreased NADPH oxidase–driven production of ROS in the endothelium.	Acetate or butyrate inhibited the lipopolysaccharide/Toll-like receptor 4 pathway and increased T-regs in the vasculature and local lymph nodes.	Robles-Vera et al91

β-HB = β-hydroxybutyrate; IL = interleukin; iNOS = inducible nitric oxide species; IV = intravenous; ox-LDL = oxidized low-density lipoprotein; SHR = spontaneously hypertensive rat; SOD2 = superoxide dismutase 2, mitochondrial; WT = wild-type; other abbreviations as in Table 1.