Table 4.
SCFAs afford protection against oxidative stress via activation of Keap1-Nrf2 pathway in animal models.
| Species | Strain/diet | SCFA | Treatment | Key findings | References |
|---|---|---|---|---|---|
| Rat | High-fat diet, 9 weeks | Butyric | NaB (300 mg/kg), every 2d, 7 weeks | ↓HDAC1 ↑H3K9ac Nrf2 promoter ↑Nrf2, SOD, GSH ↑Insulin signaling |
[91] |
| Obesity-prone rats | Butyric | 4% NaB, 12 weeks | Reversion of bone loss and body weight gain ↑nuclear Nrf2 ↑HO1, NQO1 ↑ Nrf2/GSK-3β signaling ↑ PGC-1α, TFAM |
[92] | |
| Mouse | C57BL/6 (Nrf2-/-) | Butyric | NaB (5 g/kg/day), 20 weeks | ↓ Renal oxidative damage ↓HDAC ↑Nrf2, HO1, NQ1 No Nrf2 nuclear translocation |
[93] |
| C57BL/6 with experimental autoimmune uveitis | Butyric | NaB orally (1 g/kg/day) 14d | ↓ Ocular inflammatory response ↓Th17 cells ↑Treg cells Nrf2/HO1 dependent |
[94] | |
| C57BL/6 (Nrf2-/-) diabetes-induced | Butyric | NaB (5 g/kg/day) 20 weeks | ↓ Aortic endothelial dysfunction Nrf2-dependent ↓HDAC ↑Nrf2 transcript and protein No significant Nrf2 nuclear translocation |
[66] |
Abbreviations: ERK: extracellular-signal-regulated kinase; FFAR2: free fatty acids receptor 2; GSH: glutathion; GPX2: glutathione peroxidase 2; GSK-3β: glycogen synthase kinase-3β; GR109A: G-protein-coupled receptor; HDAC1: histone deacetylase 1; HO1: heme oxygenase 1; H3K9ac; histone H3 acetylated in lysine 9/14; ICAM-1: intercellular adhesion molecule 1; IL-1β: interleukin 1 beta; JNK: Jun N-terminal kinase; LRP-1: LDL Receptor Related Protein 1; MCP-1: monocyte chemotactic protein 1; MDA: malondialdehyde; SOD1-3: superoxide dismutase 1–3; NaB: sodium butyrate; NQ1: NAD(P)H: quinone oxidoreductase-1; Nrf2: nuclear erythroid 2-related factor 2; PGC1-α: peroxisome proliferator-activated receptor γ co-activator 1 α; p38: mitogen activated (MAP) kinase p38.
Upward arrow (↑) indicates an increase and downward arrow (↓) a decrease in respective measured outcomes.