title: Anti-fibrotic effects of valproic acid: role of HDAC inhibition and associated mechanisms.
abstract: Tissue injuries and pathological insults produce oxidative stress, genetic and epigenetic alterations, which lead to an imbalance between pro- and anti-fibrotic molecules, and subsequent accumulation of extracellular matrix, thereby fibrosis. Various molecular pathways play a critical role in fibroblasts activation, which promotes the extracellular matrix production and accumulation. Recent reports highlighted that histone deacetylases (HDACs) are upregulated in various fibrotic disorders and play a central role in fibrosis, while HDAC inhibitors exert antifibrotic effects. Valproic acid is a first-line anti-epileptic drug and a proven HDAC inhibitor. This review provides the current research and novel insights on antifibrotic effects of valproic acid in various fibrotic conditions with an emphasis on the possible strategies for treatment of fibrosis.
authors.affiliation: Facility for Risk Assessment & Intervention Studies, Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: Sabbir
authors.initials: S
authors.lastname: Khan
authors.affiliation: Facility for Risk Assessment & Intervention Studies, Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: Kailash
authors.initials: K
authors.lastname: Ahirwar
authors.affiliation: Facility for Risk Assessment & Intervention Studies, Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: Gopabandhu
authors.initials: G
authors.lastname: Jena
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005355:Fibrosis; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid
keywords: HDAC inhibitors; epigenetics; fibrosis; histone acetylation; post-translational modifications; valproic acid