2011 American journal of physiology. Lung cellular and molecular physiology Mechanism / Preclinical Inhalation
2011 · Terasaki — Hydrogen Therapy Attenuates Irradiation-Induced Lung Damage by Reducing Oxidative Stress
Super-Abstract
In irradiated human lung cells and in mice given whole-thorax irradiation, molecular hydrogen (H₂) — delivered as H₂-rich PBS, H₂-enriched drinking water, or 3% H₂ inhalation — significantly reduced oxidative stress markers, apoptosis, and lung fibrosis. These are encouraging preclinical results for a potential radioprotective strategy, but the findings come from cell culture and animal experiments and cannot yet be directly applied to human cancer patients. (American Journal of Physiology: Lung Cellular and Molecular Physiology, 2011.)
Commentary
Radiation pneumonitis and subsequent lung fibrosis are serious dose-limiting toxicities of thoracic radiotherapy. Reactive oxygen species (ROS) — particularly hydroxyl radicals — generated by ionising radiation are central to this damage. Molecular hydrogen (H₂) is known to selectively scavenge hydroxyl radicals and peroxynitrite without disturbing other physiologically important ROS. This study tested H₂ as a radioprotector in two systems: human A549 lung epithelial cells irradiated at 10 Gy in H₂-rich medium, and C57BL/6J female mice irradiated at 15 Gy to the thorax, then treated with 3% inhaled H₂ gas plus H₂-enriched drinking water. In cells, H₂ reduced ROS levels (electron spin resonance, fluorescence) and improved viability. In mice, immunohistochemistry and immunoblotting at 1 week confirmed reduced acute oxidative stress and apoptosis; CT, Ashcroft scoring, and collagen deposition at 5 months showed reduced lung fibrosis. No toxicity of H₂ treatment was detected. These are sound preclinical results, but replication in human clinical trials is needed.
Key quotes
- „H(2) reduced the amount of irradiation-induced ROS in A549 cells, as shown by electron spin resonance and fluorescent indicator signals.“ — direct measurement of ROS reduction by H₂ in human lung cells
- „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.“ — the key long-term finding: reduced fibrosis in mice at 5 months post-irradiation
- „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.“ — the scientific rationale for testing H₂ as a radioprotector
Our assessment
This is a well-designed animal and cell culture (preclinical) study. Both in-vitro (A549 cells) and in-vivo (mouse) components support the hypothesis that H₂ mitigates radiation-induced lung injury. The multi-modal outcome assessment (ESR, fluorescence, IHC, CT, fibrosis scoring) adds credibility. Limitations: mouse models of thoracic irradiation do not perfectly replicate human clinical scenarios; A549 is a cancer cell line, not normal lung epithelium. No human trials have yet confirmed these results in radiotherapy patients. The „no known toxicity“ claim refers only to the doses tested in this study. These findings are promising but remain preclinical evidence only.
Study design
- Type: preclinical animal + in-vitro study · Model: A549 human lung cells (10 Gy) + C57BL/6J female mice (15 Gy thoracic irradiation) · H₂ delivery: H₂-rich PBS/medium (cells); 3% H₂ inhalation + H₂-enriched drinking water (mice)
- Result: H₂ reduced ROS, apoptosis, and acute oxidative stress (1 week); reduced lung fibrosis at 5 months post-irradiation; no H₂-related toxicity observed
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.
Source & links
Screenshot of the PubMed page
This page mirrors the published abstract (© the authors / publisher) for reference and citation. The canonical source is the PubMed record linked above. This is not medical advice.