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597 Valproic Acid-Mediated Protection Against Hyperoxic Lung Injury Via Histone Deacetylase Inhibition in a Neonatal Rat Model
  1. M Cetinkaya1,
  2. M Cansev2,
  3. F Cekmez1,
  4. C Tayman1,
  5. FE Canpolat1,
  6. IM Kafa2,
  7. E Orenlili2,
  8. S Uysal3,
  9. SU Sarıcı1
  1. 1GATA Teaching Hospital, Ankara
  2. 2Uludag˘ University Medical Faculty, Bursa
  3. 3Fatih University Medical Faculty, Ankara, Turkey

Abstract

Epigenetic mechanisms might play an important role in development of BPD. The aim of this study was to evaluate the protective effect of valproic acid (VPA), an histon deacetylase inhibitor, in hyperoxic lung injury in neonatal rat model.

Methods A total of 30 rat pups (0 days old) were divided equally into 3 groups: control, hyperoxia and hyperoxia+VPA groups. In hyperoxia groups, pups were maintained in 95% O2 for 10 days while control group was maintained in room air. VPA was administered intraperitoneally once daily for the first 10 days of life. On day 10, histopathological score, radial alveolar count, lamellar protein count, histone deacetylase activity (HDAC), proinflammatory cytokine concentrations were determined with ELISA, whereas acetylated H4 protein and caspase-3 expression were evaluated with Western-Blot analysis. Also apoptosis was evaluated with TUNEL method.

Results The histopathological score, radial alveolar count, lamellar protein count of the pups in VA group were significantly higher. VPA also preserved alveolarization significantly and fibrosis was significantly decreased in rat pups exposed to VPA treatment. HDAC activity significantly reduced with VPA treatment. The proinflammatory markers, caspase-3 expression and number of TUNEL positive cells were also significantly decreased with VPA treatment. Acetylated H4 protein expression was significantly higher in the hyperoxia+VPA group.

Conclusion All these data suggest that VPA might provide possible protective effect against hyperoxic lung injury as an histone deacetylase inhibitor. VPA exhibit these effects by preserving alveolarization, decreasing fibrosis and inflammation via decreasing HDAC activity, increasing acetylated H4 protein expression and reducing inflammation.

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