Probucol attenuates hyperoxia-induced lung injury in mice

Tomonobu Kawaguchi, Toyoshi Yanagihara, Tetsuya Yokoyama, Saiko Suetsugu-Ogata, Naoki Hamada, Chika Harada-Ikeda, Kunihiro Suzuki, Takashige Maeyama, Kazuyoshi Kuwano, Yoichi Nakanishi

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Abstract

Hyperoxic lung injury is pathologically characterized by alveolar edema, interlobular septal edema, hyaline membrane disease, lung inflammation, and alveolar hemorrhage. Although the precise mechanism by which hyperoxia causes lung injury is not well defined, oxidative stress, epithelial cell death, and proinflammatory cytokines are thought to be involved. Probucol - a commercially available drug for treating hypercholesterolemia - has been suggested to have antioxidant and antiapoptotic effects. This study aimed to assess whether probucol could attenuate hyperoxic lung injury in mice. Mice were exposed to 95% O2 for 72 h, with or without pre-treatment with 130 μg/kg probucol intratracheally. Probucol treatment significantly decreased both the number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung injury in hyperoxia-exposed mice. Probucol treatment reduced the number of cells positive for 8-hydroxyl-2′-deoxyguanosine or terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and suppressed NF-κB activation, Bax expression, and caspase-9 activation in lung tissues from hyperoxia-exposed mice. These results suggest that probucol can reduce oxidative DNA damage, apoptotic cell death, and inflammation in lung tissues. Intratracheal administration of probucol may be a novel treatment for lung diseases induced by oxidative stress, such as hyperoxic lung injury and acute respiratory distress syndrome.

Original languageEnglish
Article numbere0175129
JournalPloS one
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Kawaguchi, T., Yanagihara, T., Yokoyama, T., Suetsugu-Ogata, S., Hamada, N., Harada-Ikeda, C., Suzuki, K., Maeyama, T., Kuwano, K., & Nakanishi, Y. (2017). Probucol attenuates hyperoxia-induced lung injury in mice. PloS one, 12(4), [e0175129]. https://doi.org/10.1371/journal.pone.0175129