title: Valproic acid attenuates lipopolysaccharide-induced acute lung injury in mice.
abstract: Valproic acid (VPA) has been shown to exert anti-inflammatory and antioxidant effects in a range of diseases including septic shock. However, the effects of VPA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains not well understood. We found that VPA pretreatment attenuated the LPS-induced ALI, as evidenced by the reduced histological scores, myeloperoxidase activity, and wet-to-dry weight ratio in the lung tissues. This was accompanied by the downregulated nuclear factor kappa B (NF-κB) p65, nitric oxide, and inducible nitric oxide synthase in the lung tissues and the decreased levels of tumor necrosis factor alpha and interleukin-1β in the bronchoalveolar lavage fluid. Furthermore, VPA reduced the nuclear histone deacetylase (HDAC)3 expression whereas increased the cytoplasmic HDAC3 expression. Our results suggested that VPA attenuates the LPS-induced ALI via inhibiting the NF-κB activation probably through a mechanism depending on HDAC3 redistribution.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Mu-huo
authors.initials: MH
authors.lastname: Ji
authors.forename: Guo-min
authors.initials: GM
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.forename: Si-hai
authors.initials: SH
authors.lastname: Zhu
authors.forename: Da-peng
authors.initials: DP
authors.lastname: Gao
authors.forename: Yun-xia
authors.initials: YX
authors.lastname: Fan
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Jian-jun
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid; D015536:Down-Regulation; D006655:Histone Deacetylases / Q000096:biosynthesis / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D009195:Peroxidase / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014635:Valproic Acid / Q000627:therapeutic use*; D000099186:Histone Deacetylase 3
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D006655:Histone Deacetylases; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D014635:Valproic Acid; D000099186:Histone Deacetylase 3; C498144:Rela protein, mouse