Sodium butyrate, a HDAC inhibitor ameliorates eNOS, iNOS and TGF-β1-induced fibrogenesis, apoptosis and DNA damage in the kidney of juvenile diabetic rats

Recent reports highlighted the role of histone deacetylases (HDACs) in the pathogenesis of diabetic nephropathy (DN), but the exact molecular mechanisms by which HDAC inhibitors ameliorate DN still remain unclear. The present study was aimed to investigate the renoprotective effects of sodium butyrate (NaB) in diabetes-induced renal damages, apoptosis and fibrosis in juvenile rats. Diabetes was induced by single injection of STZ (60 mg/kg), whereas NaB (500 mg/kg/day) was administrated for 21 days by i.p. route in a pre- and post-treatment schedule. End-points of evaluation included biochemical estimation, histology, protein expression as well as apoptosis and DNA damage examinations. Post-treatment with NaB significantly decreased plasma glucose, creatinine, urea, histological alterations including the fibrosis and collagen deposition as well as decreased the HDACs activity, expression of eNOS, iNOS, α-SMA, collagen I, fibronectin, TGFβ-1, NFκB, apoptosis and DNA damage in the diabetic kidney. These results showed that NaB treatment improved the renal function and ameliorated the histological alterations, fibrosis, apoptosis and DNA damage in the kidney of juvenile rats.