Scientific Studies

Lungs and Asthma

Hydrogen is considered to be a novel antioxidant as it inhibits inflammation, removes oxygen-derived free radicals and reduces oxidative damage. This study investigated the effects of hydrogen-rich saline on plasma interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) in rats with uncontrolled hemorrhagic shock (UHS). The UHS model was induced by arterial bleeding and tail amputation. The rats were randomly divided into: Group A (sham-operated group), Group B [shock + intravenously (IV) injected saline], Group C (shock + IV-injected hydrogen-rich saline), Group D [shock + intraperitoneally (IP) injected saline] and Group E (shock + IP-injected hydrogen-rich saline). The survival rate 24 h after successful resuscitation was calculated. The mean arterial pressure and heart rate were recorded at 0, 30, 90 and 210 min. The plasma levels of IL-6, TNF-α, SOD and MDA were measured at 0, 90 and 210 min. The survival rate of each group was 100% and the hemodynamics among the experimental groups were not significantly different. At 90 and 210 min, the levels of IL-6, TNF-α and MDA in Groups C and E were lower than those of Groups B and D, while the SOD levels were higher than those of Groups B and D (P ≤ 0.01). At 90 min, the levels of IL-6, TNF-α and MDA in Groups B and C were lower than those of Groups D and E, respectively (P ≤ 0.01). Hydrogen-rich saline has anti-inflammatory and anti-oxidative effects in UHS. In conclusion, the results showed that itravenous injection of hydrogen-rich saline is more effective than intraperitonal injection.

Hydrogen has been reported to selectively quench detrimental reactive oxygen species, particularly hydroxyl radical, and to prevent myocardial or hepatic ischemia/reperfusion injury in multiple models. The aim of this study is to investigate whether hydrogen protects against severe burn-induced acute lung injury in rats. Rats were divided into four groups: sham plus normal saline, burn injury plus normal saline, burn injury plus hydrogen-rich saline, and burn injury plus edaravone. Animals were given full-thickness burn wounds (30% TBSA) using boiling water, except the sham group that was treated with room temperature water. The rats in hydrogen group received 5 ml/kg of hydrogen-rich saline, sham and burn controls obtained the same amount of saline, and the edaravone group was treated with 9 mg/kg of edaravone in saline. Lactated Ringer's solution was given at 6 hours postburn. The lungs were harvested 12 hours postburn for laboratory investigations. Severe burns with delayed resuscitation rapidly caused lung edema and impaired oxygenation in rats. These dysfunctions were ameliorated by administration of hydrogen-rich saline or edaravone. When compared with the burn injury plus normal saline group, hydrogen-rich saline or edaravone group significantly attenuated the pulmonary oxidative products, such as malondialdehyde, carbonyl, and 8-hydroxy-2'-deoxyguanosine. Furthermore, administration of hydrogen-rich saline or edaravone dramatically reduced the pulmonary levels of pulmonary inflammation mediators and myeloperoxidase. Intraperitoneal administration of hydrogen-rich saline improves pulmonary function by reducing oxidative stress and inflammatory response in severe burn-induced acute lung injury.


Lung transplantation is a well-established treatment of end-stage lung disease; however, it is limited by a shortage of donor lungs. To overcome this problem, donation after cardiac death (DCD) and ex vivo lung perfusion (EVLP) are being widely investigated. In this study, the effect of hydrogen gas, a known antioxidant, was investigated on a DCD lung model during EVLP.


Ten pigs were randomized into either a control (n = 5) or a hydrogen group (n = 5). After fibrillation by electric shock, no further treatment was administered in order to induce warm ischaemic injury for 1 h. The lungs were then procured, followed by 4 h of EVLP. During EVLP, the lungs were ventilated with room air in the control group, and with 2% hydrogen gas in the hydrogen group. Oxygen capacity (OC), pulmonary vascular resistance (PVR) and peak airway pressure (PAP) were measured every hour, and the expressions of interleukin-1 beta (IL-1β), IL-6 (IL-6), IL-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) were evaluated in lung tissue after EVLP. Pathological evaluations were performed using lung injury severity (LIS) scores and the wet/dry ratio was also measured.


The OC in the hydrogen group was higher than in the control group, but the difference was not statistically significant (P = 0.0862). PVR (P = 0.0111) and PAP (P = 0.0189) were statistically significantly lower in the hydrogen group. Compared with the control group, the hydrogen group had a statistically significantly lower expression of IL-1β (P = 0.0317), IL-6 (P = 0.0159), IL-8 (P = 0.0195) and TNF-α (P = 0.0159). The LIS scores (P = 0.0358) and wet/dry ratios (P = 0.040) were also significantly lower in the hydrogen group.


Hydrogen gas inhalation during EVLP improved the function of DCD lungs, which may increase the utilization of DCD lungs.


Mechanical ventilation (MV) can provoke oxidative stress and an inflammatory response, and subsequently cause ventilator-induced lung injury (VILI), a major cause of mortality and morbidity of patients in the intensive care unit. Inhaled hydrogen can act as an antioxidant and may be useful as a novel therapeutic gas. We hypothesized that, owing to its antioxidant and anti-inflammatory properties, inhaled hydrogen therapy could ameliorate VILI.


VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg without positive end-expiratory pressure, FiO(2) 0.21). The mice were randomly assigned to treatment groups and subjected to VILI with delivery of either 2% nitrogen or 2% hydrogen in air. Sham animals were given same gas treatments for two hours (n = 8 for each group). The effects of VILI induced by less invasive and longer exposure to MV (tidal volume of 10 ml/kg, 5 hours, FiO(2) 0.21) were also investigated (n = 6 for each group). Lung injury score, wet/dry ratio, arterial oxygen tension, oxidative injury, and expression of pro-inflammatory mediators and apoptotic genes were assessed at the endpoint of two hours using the high-tidal volume protocol. Gas exchange and apoptosis were assessed at the endpoint of five hours using the low-tidal volume protocol.


Ventilation (30 ml/kg) with 2% nitrogen in air for 2 hours resulted in deterioration of lung function, increased lung edema, and infiltration of inflammatory cells. In contrast, ventilation with 2% hydrogen in air significantly ameliorated these acute lung injuries. Hydrogen treatment significantly inhibited upregulation of the mRNAs for pro-inflammatory mediators and induced antiapoptotic genes. In the lungs treated with hydrogen, there was less malondialdehyde compared with lungs treated with nitrogen. Similarly, longer exposure to mechanical ventilation within lower tidal volume (10 mg/kg, five hours) caused lung injury including bronchial epithelial apoptosis. Hydrogen improved gas exchange and reduced VILI-induced apoptosis.


Inhaled hydrogen gas effectively reduced VILI-associated inflammatory responses, at both a local and systemic level, via its antioxidant, anti-inflammatory and antiapoptotic effects.