Document Detail


Valproic acid attenuates proteinuria and kidney injury.
MedLine Citation:
PMID:  21868496     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Katrien Van Beneden; Caroline Geers; Marina Pauwels; Inge Mannaerts; Dierik Verbeelen; Leo A van Grunsven; Christiane Van den Branden
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-08-25
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  22     ISSN:  1533-3450     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-03     Completed Date:  2011-11-21     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1863-75     Citation Subset:  IM    
Affiliation:
Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Acute Kidney Injury / prevention & control
Animals
Antibiotics, Antineoplastic
Disease Models, Animal
Doxorubicin
Drug Evaluation, Preclinical
Female
Glomerulosclerosis, Focal Segmental / chemically induced,  drug therapy*
Histone Deacetylase Inhibitors / therapeutic use*
Mice
Mice, Inbred BALB C
Proteinuria / prevention & control
Valproic Acid / therapeutic use*
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Histone Deacetylase Inhibitors; 23214-92-8/Doxorubicin; 99-66-1/Valproic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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