title: Probucol attenuates hyperoxia-induced lung injury in mice.
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.
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Toyoshi
authors.identifier: http://orcid.org/0000-0002-2212-0631
authors.initials: T
authors.lastname: Yanagihara
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Saiko
authors.initials: S
authors.lastname: Suetsugu-Ogata
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hamada
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Harada-Ikeda
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takashige
authors.initials: T
authors.lastname: Maeyama
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kuwano
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D018496:Hyperoxia / Q000150:complications*; D055370:Lung Injury / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009249:NADP / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D009249:NADP; D011341:Probucol