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275 PREVENTION OF CHRONIC LUNG DISEASE IN THE PREMATURE INFANT: “AN INDIAN FLAVOR.”
  1. L. Cerny,
  2. Y. Wang,
  3. J. Santos,
  4. R. Sakurai,
  5. S. Hean,
  6. J. S. Torday,
  7. V. K. Rehan
  1. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA

Abstract

Background Despite numerous advances in the treatment and prevention of respiratory distress syndrome (RDS) in the premature infant, chronic lung disease (CLD), a sequela of RDS remains extremely common. Its pathogenesis, treatment, and prevention remain incompletely understood. Exposure to hyperoxia, inflammation, and ventilation by the premature lung are the principal causative factors. Because of the well-known antioxidant and anti-inflammatory properties of curcumin [1,7-bis (4′-hydroxy-3′-methoxyphenyl)-1,6-heptadiene-3,5-dione], the naturally occurring pigment derived from the Indian spice tumeric, we hypothesized that it would be useful in preventing CLD of the newborn.

Objectives To determine the effects of curcumin on the expression of the well-established markers of lung alveolar homeostasis and disease that have been previously validated in our laboratory.

Design/Methods Lung explants, isolated fetal rat lung fibroblasts, or alveolar type II cells at embryonic (e) day 19.5 (term = e22) from Sprague-Dawley rat fetuses were treated in culture with curcumin (0-100 μM) for up to 48 h. The explants were maintained in Waymouth's medium and isolated fibroblasts and ATII cells were cultured in DMEM at 37°C/5% CO2. Subsequently, [3 H]choline incorporation into saturated phosphatidylcholine and [3 H]triolein uptake, both markers of surfactant phospholipid synthesis, were examined. Further, mRNA and proteins were extracted, and using RT-PCR and Western hybridization, the expression of the well-characterized markers of lung alveolar health and disease were analyzed. These included the expression of peroxisome proliferator-activated receptorγ, adipocyte differentiation-related protein, surfactant protein-B, and α smooth muscle actin.

Results Our data suggest that curcumin augments the expression of some but not all alveolar fibroblast and alveolar type II specific markers that are known to be critical in maintaining alveolar homeostasis. The studies to determine whether curcumin prevents hyperoxia- and infection-induced lung injury are in progress.

Conclusions From these data, we conclude that curcumin administration may stimulate specific molecular pathways, which may help in preventing hyperoxia- and inflammation-induced CLD in the premature infant.

Supported in part by NIH grants HL75405A (V.K.R. and J.S.T.) and HL55268 (J.S.T. and V.K.R.), Philip Morris USA Inc. and Philip Morris International, Tobacco-Related Disease Research Program (14RT-0073), and March of Dimes.

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