Suppression of HDAC2 by sodium butyrate alleviates apoptosis of kidney cells in db/db mice and HG‑induced NRK‑52E cells.

Butyrate is short‑chain fatty acid, which is produced by intestinal microbiota metabolizing dietary fibers. Butyrate participates in various physiological processes predominantly by activating G‑coupled‑receptors, inhibiting histone deacetylases (HDACs) and serving as an energy substrate. Previous studies have shown that butyrate plays a protective role in diabetic nephropathy (DN); however, the exact mechanism remains unclear. The present study identified that providing sodium butyrate (NaBu) by gavage relieved renal damage and apoptosis in db/db mice, which is a widely used type 2 DN model. In vitro, NaBu suppressed high glucose (HG)‑induced apoptosis in normal rat kidney tubular epithelial (NRK‑52E) cells. Of the eleven HDACs (HDAC1‑11) studied, only the mRNA expression of HDAC2 was attenuated by NaBu in NRK‑52E cells under the HG condition. Overexpression of HDAC2 offset the anti‑apoptotic effect of NaBu. NaBu also suppressed HG‑induced oxidative stress. Additionally, H2O2 induced an upregulation of HDAC2 in NRK‑52E cells, while NaBu inhibited this process. Mechanistically, NaBu acted as an antioxidant in HG‑induced NRK‑52E cells and suppressed HG‑induced apoptosis of NRK‑52E cells through inhibiting HDAC2 by virtue of its anti‑oxidative property.