Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress

Am J Physiol Lung Cell Mol Physiol. 2011 Oct;301(4):L415-26. doi: 10.1152/ajplung.00008.2011. Epub 2011 Jul 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Apoptosis Regulatory Proteins / analysis
  • Apoptosis Regulatory Proteins / biosynthesis*
  • Blotting, Western
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • DNA Damage / drug effects
  • DNA Damage / radiation effects
  • Female
  • Humans
  • Hydrogen / pharmacology*
  • Hydroxyl Radical / antagonists & inhibitors*
  • Hydroxyl Radical / metabolism
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / radiation effects
  • Mice
  • Oxidative Stress / drug effects*
  • Oxidative Stress / radiation effects
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / prevention & control
  • Radiation Dosage
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / metabolism
  • Thorax / drug effects*
  • Thorax / metabolism
  • Thorax / radiation effects
  • Tomography, X-Ray Computed
  • X-Rays / adverse effects

Substances

  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Reactive Oxygen Species
  • Hydroxyl Radical
  • Hydrogen