title: Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress.
abstract: Molecular hydrogen (H(2)) is an efficient antioxidant that diffuses rapidly across cell membranes, reduces reactive oxygen species (ROS), such as hydroxyl radicals and peroxynitrite, and suppresses oxidative stress-induced injury in several organs. ROS have been implicated in radiation-induced damage to lungs. Because prompt elimination of irradiation-induced ROS should protect lung tissue from damaging effects of irradiation, we investigated the possibility that H(2) could serve as a radioprotector in the lung. Cells of the human lung epithelial cell line A549 received 10 Gy irradiation with or without H(2) treatment via H(2)-rich PBS or medium. We studied the possible radioprotective effects of H(2) by analyzing ROS and cell damage. Also, C57BL/6J female mice received 15 Gy irradiation to the thorax. Treatment groups inhaled 3% H(2) gas and drank H(2)-enriched water. We evaluated acute and late-irradiation lung damage after H(2) treatment. H(2) reduced the amount of irradiation-induced ROS in A549 cells, as shown by electron spin resonance and fluorescent indicator signals. H(2) also reduced cell damage, measured as levels of oxidative stress and apoptotic markers, and improved cell viability. Within 1 wk after whole thorax irradiation, immunohistochemistry and immunoblotting showed that H(2) treatment reduced oxidative stress and apoptosis, measures of acute damage, in the lungs of mice. At 5 mo after irradiation, chest computed tomography, Ashcroft scores, and type III collagen deposition demonstrated that H(2) treatment reduced lung fibrosis (late damage). This study thus demonstrated that H(2) treatment is valuable for protection against irradiation lung damage with no known toxicity.
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan. terasaki@nms.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Terasaki
authors.forename: Ikuroh
authors.initials: I
authors.lastname: Ohsawa
authors.forename: Mika
authors.initials: M
authors.lastname: Terasaki
authors.forename: Mikiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kunugi
authors.forename: Kang
authors.initials: K
authors.lastname: Dedong
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Urushiyama
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Amenomori
authors.forename: Mayuko
authors.initials: M
authors.lastname: Kaneko-Togashi
authors.forename: Naomi
authors.initials: N
authors.lastname: Kuwahara
authors.forename: Arimi
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamimura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohta
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000096:biosynthesis*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006801:Humans; D006859:Hydrogen / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D011829:Radiation Dosage; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013909:Thorax / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D014057:Tomography, X-Ray Computed; D014965:X-Rays / Q000009:adverse effects
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D006859:Hydrogen