Protective Effects of Valproic Acid, a Histone Deacetylase Inhibitor, Against Hyperoxic Lung Injury in a Neonatal Rat Model

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 May 5

PMID 25938838

Citations 10

Authors

Merih Cetinkaya

Mehmet Cansev

Ferhat Cekmez

Cuneyt Tayman

Fuat Emre Canpolat

Ilker Mustafa Kafa

Esra Orenlili Yaylagul

Boris W Kramer

Serdar Umit Sarici

Affiliations

Soon will be listed here.

Abstract

Objective: 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.

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