The Renoprotective Effects of Sodium Valproate as a Histone Deacetylase Inhibitor on Diabetic Nephropathy

Diabetic nephropathy (DN), as the most common cause of end-stage renal failure, caused by protein kinase C pathway and reactive oxygen species. Recent studies demonstrated importance of epigenetic processes such as histone acetylation and the role of histone deacetylases (HDAC) and histone acetyltransferase in the development of this silent epidemic. Sodium valproate (VA) is known as a histone deacetylase inhibitor(HDACi). DN must be prevented and treated because it is prevalent and important.
In this study, scientific articles indexed in databases "Web of science, Scopus, PubMed, SID, ISI" were studied using key words "Sodium Valproate, Diabetic Nephropathies, Histone Deacetylase Inhibitors".
FINDINGS: VA can prevent the degradation podocytes and renal cells through the autophagy and reduce proteinuria in the DN condition. In addition, VA, as an HDAC, prevented apoptosis of podocytes, thus it improves DN. Because HDAC class I involved in renal fibrogenesis and fibroblast activation by modulation of TGF-β signaling, sodium valproate promotes antifibrotic effects logically. VA can regulate NF-κB signaling, thereby exert an anti-inflammatory effect in podocytes. HDAC inhibition decreased eNOS mRNA but paradoxically increased activity of eNOS promoter, probably because of inducing an eNOS mRNA-destabilizing factor. Sodium valproate as a HDACi has the high renoprotective effect in laboratory studies with DN models.
It is expected that sodium valproate will be used as the prevention or treatment of DN in the future after the clinical trials.