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

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 deacety-lase (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, bio-chemical 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