Cetinkaya, MerihCekmez, FerhatTayman, CuneytCanpolat, Fuat EmreKramer, Boris W.Sarici, Serdar Umit2023-10-062023-10-062015-05-04Cetinkaya, M. vd. (2015). "Protective effects of valproic acid, a histone deacetylase inhibitor, against hyperoxic lung injury in a neonatal rat model". PLoS ONE, 10(5).1932-6203https://doi.org/10.1371/journal.pone.0126028https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126028http://hdl.handle.net/11452/34237Objective: Histone acetylation and deacetylation may play a role in the pathogenesis of inflammatory lung diseases. We evaluated the preventive effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on neonatal hyperoxic lung injury. Methods: Forty newborn rat pups were randomized in normoxia, normoxia+VPA, hyperoxia and hyperoxia+VPA groups. Pups in the normoxia and normoxia+VPA groups were kept in room air and received daily saline and VPA (30 mg/kg) injections, respectively, while those in hyperoxia and hyperoxia+VPA groups were exposed to 95% O2 and received daily saline and VPA (30 mg/kg) injections for 10 days, respectively. Growth, histopathological, biochemical and molecular biological indicators of lung injury, apoptosis, inflammation, fibrosis and histone acetylation were evaluated. Results: VPA treatment during hyperoxia significantly improved weight gain, histopathologic grade, radial alveolar count and lamellar body membrane protein expression, while it decreased number of TUNEL(+) cells and active Caspase-3 expression. Expressions of TGFβ3 and phospho-SMAD2 proteins and levels of tissue proinflammatory cytokines as well as lipid peroxidation biomarkers were reduced, while anti-oxidative enzyme activities were enhanced by VPA treatment. VPA administration also reduced HDAC activity while increasing acetylated H3 and H4 protein expressions. Conclusions: The present study shows for the first time that VPA treatment ameliorates lung damage in a neonatal rat model of hyperoxic lung injury. The preventive effect of VPA involves HDAC inhibition.eninfo:eu-repo/semantics/openAccessScience & Technology - Other topicsGene-expressionBCL-2PathogenesisExposurePathwayLPSBAXRattusAnimalsBiomarkersBody weightCaspase 3Disease models, AnimalHistone deacetylase inhibitorsHyperoxiaLung injuryOxidation-reductionOxidative stressProtective agentsProto-oncogene proteins c-bcl-2RatsValproic acidArticle0003539430001322-s2.0-8492937806510525662067Multidisciplinary sciencesHistone deacetylase inhibitors; Valproic acid; AnimalsCaspase 3Histone H3Histone H4Interleukin 1betaInterleukin 6Protein bcl 2Smad2 proteinTransforming growth factor beta1Transforming growth factor beta3Tumor necrosis factor alphaValproic acidBiological markerHistone deacetylase inhibitorProtective agentProtein bcl 2Animal experimentAnimal modelAnimal tissueApoptosisArticleCell countDrug efficacyDrug responseEnzyme activityHistone acetylationHyperoxiaLipid peroxidationLung injuryNonhumanPneumoniaProtein expressionProtein functionRatWeight gainAnimalBody weightComplicationDisease modelLung injuryMetabolismMortalityOxidation reduction reactionOxidative stressPathology