title: Valproic acid attenuates proteinuria and kidney injury.
abstract: Inhibitors of histone deacetylase (HDAC) have anti-inflammatory and antifibrotic effects in several organs and tissues, but their effect on the progression of renal disease is unknown. Here, we studied the effect of valproic acid in adriamycin-induced nephropathy in mice. Administration of valproic acid before kidney injury prevented the development of proteinuria and the onset of glomerulosclerosis. Even after postponing treatment until the peak of adriamycin-induced proteinuria, valproic acid rapidly decreased the quantity of proteinuria and attenuated the progression of renal disease. Valproic acid abrogated the decrease in glomerular acetylation observed during adriamycin-induced nephropathy. Furthermore, valproic acid attenuated the significant upregulation of profibrotic and proinflammatory genes, the deposition of collagen, and the infiltration of macrophages into the kidney. Valproic acid decreased glomerular apoptosis and proliferation induced by adriamycin. Ultrastructural studies further supported the protective effect of valproic acid on podocytes in this model. Taken together, these data suggest that HDACs contribute to the pathogenesis of renal disease and that HDAC inhibitors may have therapeutic potential in CKD.
authors.affiliation: Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Van Beneden
authors.forename: Caroline
authors.initials: C
authors.lastname: Geers
authors.forename: Marina
authors.initials: M
authors.lastname: Pauwels
authors.forename: Inge
authors.initials: I
authors.lastname: Mannaerts
authors.forename: Dierik
authors.initials: D
authors.lastname: Verbeelen
authors.forename: Leo A
authors.initials: LA
authors.lastname: van Grunsven
authors.forename: Christiane
authors.initials: C
authors.lastname: Van den Branden
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control; D000818:Animals; D000903:Antibiotics, Antineoplastic; D004195:Disease Models, Animal; D004317:Doxorubicin; D004353:Drug Evaluation, Preclinical; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000188:drug therapy*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D011507:Proteinuria / Q000517:prevention & control; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000903:Antibiotics, Antineoplastic; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; D004317:Doxorubicin