TY - JOUR
T1 - Sodium butyrate, a HDAC inhibitor ameliorates eNOS, iNOS and TGF-β1-induced fibrogenesis, apoptosis and DNA damage in the kidney of juvenile diabetic rats
AU - Khan, Sabbir
AU - Jena, Gopabandhu
N1 - Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - DNA damage
KW - Fibrosis
KW - HDAC inhibitor
KW - Juvenile diabetes
KW - Sodium butyrate
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U2 - 10.1016/j.fct.2014.08.010
DO - 10.1016/j.fct.2014.08.010
M3 - Article
C2 - 25158305
AN - SCOPUS:84908051558
SN - 0278-6915
VL - 73
SP - 127
EP - 139
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
ER -