Hydrogen Therapy may be a Novel and Effective Treatment for COPD

The protective effect of hydrogen (H2) on ROS-induced diseases has been proved by many researches, which demonstrated that through eliminating •OH and •ONOO–, H2 could effectively attenuate lipid and DNA peroxidation, improve cellular antioxidant capacity, and then protect cells against oxidant damage. Most of free radicals in human body are ROS, including O2•–,•OH, H2O2, NO•,•ONOO–, and so on. Under normal circumstances cells are able to maintain an adequate homeostasis between the formation and removal of ROS through particular enzymatic pathways or antioxidants. But under some pathological conditions, the balance is disturbed, leading to oxidative stress and various diseases, such as chronic obstructive pulmonary disease (COPD). Studies have shown that ROS played a pivotal role in the development of COPD and some antioxidants were effective in the protection against the damaging effects of oxidative stress. Therefore, we hypothesize that owing to its peculiarity to eliminate toxic ROS, hydrogen therapy may be a novel and effective treatment for COPD.


IntroductIon
Hydrogen (H 2 ), a colorless, tasteless, odorless, non-irritating, and highly flammable diatomic gas, was generally regarded as physiologic inert gas in hyperbaric medicine. In 1975and 2001, Dole et al. (1975 and Gharib et al. (2001) separately reported that H 2 under a high pressure might be a therapeutic gas for cancer and parasite-induced liver inflammation by eliminating toxic ROS. In 2007, Ohsawa et al. (2007) found that 2% H 2 inhalation exhibited antioxidant and anti-apoptotic activities by selectively reducing cytotoxic oxygen radicals. The importance of H 2 immediately drew widespread concerns and it is proved to be effective for many ROS-related diseases, such as hepatic and cardiac hypoxia-ischemia injury, inflammation injury caused by small intestine transplantation and neonatal hypoxia-ischemia injury (Fukuda et al., 2007;Buchholz et al., 2008;Cai et al., 2008;Hayashida et al., 2008). Besides, other ways to administrate H 2 , such as drinking H 2 -saturated water, intraperitoneal and intravenous injection of H 2 -saturated saline, were also effective to many disorders, such as cerebral hypoxiaischemia injury, human type II diabetes, nephrotoxicity induced by cisplatin, Parkinson's disease and atherosclerosis in apolipoprotein Chen et al., 2009;Mao et al., 2009;Zheng et al., 2009;Oharazawa et al., 2010). All these evidences show that molecule H 2 is effective to diseases related to oxidative stress, which may include chronic obstructive pulmonary disease (COPD).

chronIc obstructIve pulmonary dIsease
Chronic obstructive pulmonary disease is a complex multifactorial disease mainly composed of chronic bronchitis and pulmonary emphysema, which is characterized by not fully reversible airflow limitation. The major feature of COPD is generally accepted as abnormal response to injury, chronic inflammation, excessive activation of macrophages, neutrophils, T lymphocytes, and fibroblasts in the lung. People even with mild COPD often mani-Hydrogen therapy may be a novel and effective treatment for COPD

Faculty of Naval Medicine, Department of Diving Medicine, Second Military Medical University, Shanghai, People's Republic of China
The protective effect of hydrogen (H 2 ) on ROS-induced diseases has been proved by many researches, which demonstrated that through eliminating OH and ONOO−, H 2 could effectively attenuate lipid and DNA peroxidation, improve cellular antioxidant capacity, and then protect cells against oxidant damage. Most of free radicals in human body are ROS, including O O 2   −, , H H 2 O 2 , NO  , , ONOO− and so on. Under normal circumstances cells are able to maintain an adequate homeostasis between the formation and removal of ROS through particular enzymatic pathways or antioxidants. But under some pathological conditions, the balance is disturbed, leading to oxidative stress and various diseases, such as chronic obstructive pulmonary disease (COPD). Studies have shown that ROS played a pivotal role in the development of COPD and some antioxidants were effective in the protection against the damaging effects of oxidative stress. Therefore, we hypothesize that owing to its peculiarity to eliminate toxic ROS, hydrogen therapy may be a novel and effective treatment for COPD.
nucleus. Second, as H 2 selectively reacts with OH and ONOO − , other important ROS (e.g., H 2 O 2 and O 2 − ) involved in cell signaling are not decreased, so the metabolic oxidation-reduction reactions are not disturbed. Third, the tissue compatibility of H 2 is stronger than many other oxidant scavengers. Especially, in lung the application of H 2 has some unique benefits. People have inhaled H 2 for hundreds of years in diving and it is already proved to be very safe for inhalation. Moreover, inhaled H 2 can easily reach the lung to play a therapeutic role. In addition, because of the special anatomical structure of lung, H 2 can reach lung cells easily and quickly; Furthermore, if H 2 inhalation is applied as a treatment, H 2 will act on lung directly, leading to a better therapeutic effect. In conclusion, as COPD has shown an increase in mortality in recent years, we hope H 2 will successfully control the tread due to its potential protective effect. reversible airway narrowing by constricting airway smooth muscle (Kawikova et al., 1996). Second, oxidants can promote inflammation by activating NF-kB and other pathways. Finally, oxidative stress can lead to a proteinase-antiproteinase imbalance (Park et al., 2009). hypothesIs Our hypothesis is that H 2 may be a unique, effective, and specific treatment for COPD. Given the fact that H 2 can eliminate ROS such as OH and ONOO − and ROS is an important factor in the pathogenic process in COPD, we hypothesize that H 2 may be potentially effective for COPD by preventing its occurrence, exacerbation, and slowing its process.
Compared to other oxidant scavengers, H 2 has its special advantages. First, because of its small molecular weight, H 2 can easily penetrate bio-membranes and diffuse into cytosol, mitochondria, and