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. 2022 Aug 9;13:961536. doi: 10.3389/fmicb.2022.961536

Table 1.

Application of butyrate in vivo and in vitro model of DKD.

Type Model species Mode and dose Results References
STZ-induced juvenile male SD rats Sodium butyrate (500 mg/kg/day) by intraperitoneal injection HDACs activity↓; BG↓; SCr↓, BUN↓; NOS↓, iNOS↓; a-SMA↓; collagen I↓; fibronectin↓; TGF-β1↓; NF-κB↓; apoptosis↓; DNA damage↓ Khan and Jena (2014)
STZ-induced C57BL/6 mice and Nrf2−/− mice Sodium butyrate diet (5 g/kg/day) BG (−); UACR↓; mesangial matrix↓; TGF-β1↓; CTGF↓; PAI-1↓; HDAC activity↓; Nrf2↑ Dong et al. (2017)
db/db mice Sodium butyrate (1 g/kg/day) by oral gavage BG (−); UACR↓; apoptosis↓ (BCL-2↑; Bax↓; caspase-3↓) Du et al. (2020a)
db/db mice Sodium butyrate (1 g/kg/day) diet BG (−); BW (−); mesangial matrix↓; UACR (↓); collagen IV↓; PAI-1↓; a-SMA↓; CTGF↓; P311↓; miR-7a-5p↑; TGF-β1↓ Du et al. (2020b)
In STZ-induced C57BL/6 mice Sodium butyrate 100 mg/ (kg·48 h) by intraperitoneal injection BW (−); FINS (−); blood lipid spectrum (−); RBG↓; FBG↓; IR↓; UACR↓; SCr↓; BUN↓; cystatin C↓; NF-κB↓; renal fibrosis↓ Huang et al. (2020)
vivo db/db mice Sodium butyrate (5 g/kg/day) by intraperitoneal injection BW↓; BG (−); UACR↓; glomerular and tubular injuries↓ Yang et al. (2021)
STZ-induced C57BL/6 mice Sodium butyrate (50 mM) dissolved and administered ad libitum in drinking water BG (−); UACR↓; podocytes/glomerulus↓; collagen-PSR↓; macrophage (CD68+) ↓ Li et al. (2020)
STZ-induced juvenile male SD rats Sodium butyrate (8 g/l) dissolved and administered ad libitum in drinking water H3 acetylation↑; nitrotyrosine accumulation↑; p66Shc↑, albuminuria↑ Bock et al. (2013)
db/db mice Sodium butyrate (1 g/kg/day) diet Serum butyrate↑; SCr↓; BUN↓; and UACR↓; ZO-1↑; occludin↑ Tang et al. (2022)
STZ-induced SD rats Sodium butyrate (300 mg/kg) by oral gavage Serum and fecal butyrate↑; BG↓; BUN↓; eGFR↓; fibronectin↓; collagen IV↓; LC3↑; LC3BII/I↑; autophagosomes↑; mTOR↓; AMPK↑ Cai et al. (2022)
mouse kidney mesangial cell (SV40-MES 14 cells) Sodium butyrate (5 mM) lncRNA (+); mRNA (+) Yang et al. (2021)
Mouse glomerular mesangial cells (SV40-MES 13) Sodium butyrate (5 mM) Oxidative stress↓ (ROS↓, MDA↓, SOD↑); inflammation ↓ (ICAM-1↓, MCP-1↓, IL-1β↓) Huang et al. (2017)
In Mouse glomerular mesangial cells (SV40-MES 13) Sodium butyrate (5 mM) ROS↓; MDA↓; MCP-1↓; IL-1β↓; NF-κB activation↓ Huang et al. (2020)
vitro Rat kidney tubular epithelial (NRK52E) cells Sodium butyrate (0.1, 0.5, or 1.0 mM) HDAC2↓; BCL-2↑; Bax↓; caspase-3↓; oxidative stress ↓ (ROS↓, SOD↑, LDH↓) Dong et al. (2017)
Mouse mesangial cells (SV40-MES-13) Sodium butyrate (0.5 mM) Collagen IV↓; PAI-1↓; a-SMA↓; CTGF↓; P311↓; miR-7a-5p↑; TGF-β1↓ Du et al. (2020b)
Mouse kidney tubular epithelial cells and podocytes Sodium butyrate (3.2 mM) IL-6↓; fibronectin↓; TGF-β↓; TNF-α↓; MCP-1 Li et al. (2020)

(−) no effect; (+) have an effect; STZ, streptozotocin; HDAC, histone deacetylase; HG, high glucose; eNOS, endothelial nitric oxide synthase; iNOS, inducible nitric oxide synthase; a-SMA, alpha smooth muscle actin; UACR, the ratio of urinary albumin to creatinine; TGF-β, transforming growth factor-β; CTGF, connective tissue growth factor; PAI-1, plasminogen activator inhibitor-1; Nrf2, nuclear factor erythroid 2-related factor 2; FINS, fasting insulin; BG, blood glucose; FBG, fasting blood glucose; RBG, random blood glucose; BW, body weight; SCr, serum creatinine; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; lncRNA, long non-coding RNA; mRNA, messenger RNA; IL-1β, interleukin-1β; IL-6, interleukin-6; ROS, reactive oxygen species; MDA, Malondialdehyde; SOD, superoxide dismutase; LDH, lactate dehydrogenase; NF-κB, nuclear factor kappa B; ICAM-1, intercellular adhesion molecule 1; MCP-1, monocyte chemotactic protein 1; TNF-α, tumor necrosis factor-α; BCL-2, B-cell lymphoma-2; Bax, BCL-2-Acssocisted X; ZO-1, zona occludens-1; IR, insulin resistance; AMPK, AMP-activated protein kinase; mTOR, mammalian target of rapamycin; LC3, an autophagy marker.