Evaluation of the therapeutic effects of nebulized inhalation of hydrogen-rich water on primary blast lung injury in C57BL/6 mice.

BACKGROUND

Primary blast lung injury is a common and severe consequence of explosion events, characterized by immediate and delayed effects such as apnea and rapid shallow breathing. The overpressure generated by blasts leads to alveolar and capillary damage, resulting in ventilation-perfusion mismatch and increased intrapulmonary shunting. This reduces the effective gas exchange area, causing hypoxemia and hypercapnia. Hydrogen (H2), a small-molecular-weight, nonpolar diatomic molecule, has shown potential in treating various diseases due to its antioxidant and anti-inflammatory properties. This study evaluates the therapeutic effects of nebulized hydrogen-rich water on primary blast lung injury in C57BL/6 mice and explores the underlying mechanisms.

METHODS

C57BL/6 mice (n = 150), aged 6-8 weeks, were randomly divided into 2 groups: the blast injury control group (n = 75) and the nebulized hydrogen-rich water treatment group (n = 75). Mice were exposed to a blast overpressure of 266 ± 9.156 kPA and treated with either nebulized hydrogen-rich water or sterile injection water immediately postinjury. Observations were made at 6, 12, 24, and 48 hours postinjury. Lung function was assessed using whole-body plethysmography, and arterial blood gases were analyzed. Lung tissue was examined histologically and biochemically for markers of inflammation and oxidative stress.

RESULTS

The survival rates at different time points postinjury in the nebulized hydrogen-rich water treatment group were significantly higher than those in the blast injury control group (6 hours postinjury: 89.3% vs 78.6%; 12 hours postinjury: 81.3% vs 72%; 24 hours postinjury: 81.3% vs 61.3%, P < .01). Lung function tests revealed significant improvements in tidal volume (12 hours postinjury: 0.11 ± 0.018 vs 0.08 ± 0.016, 24 hours postinjury: 0.16 ± 0.013 vs 0.12 ± 0.013, 48 hours postinjury: 0.18 ± 0.02 vs 0.13 ± 0.014), respiratory rate (6 hours postinjury: 235.07 ± 12.82 vs 268.29 ± 13.73; 12 hours postinjury: 265.47 ± 10.06 vs 342.16 ± 16.34; 24 hours postinjury: 248.20 ± 9.28 vs 352.80 ± 15.99; 48 hours postinjury: 226.12 ± 15.81 vs 318.18 ± 15.81), and minute ventilation (12 hours postinjury: 22.05 ± 3.46 vs 15.93 ± 3.68; 24 hours postinjury: 27.30 ± 2.15 vs 21.62 ± 2.48; 48 hours postinjury: 37.48 ± 3.93 vs 28.32 ± 2.98) in the nebulized hydrogen-rich water treatment group (P < .01). Arterial blood gas analysis indicated better oxygenation and reduced hypercapnia in the nebulized hydrogen-rich water treatment group (P < .05). Histologic examination showed reduced lung edema and hemorrhage in the nebulized hydrogen-rich water treatment group. Levels of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor α) and oxidative stress markers (ie, malondialdehyde) were significantly lower, whereas antioxidant enzyme (total superoxide dismutase) activity was higher in the nebulized hydrogen-rich water treatment group compared with the blast injury control group (P < .01). Arterial blood gas analysis indicated better oxygenation and reduced hypercapnia in the nebulized hydrogen-rich water treatment group (P < .05). Histologic examination showed reduced lung edema and hemorrhage in the nebulized hydrogen-rich water treatment group. Levels of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor α) and oxidative stress markers (ie, malondialdehyde) were significantly lower, whereas antioxidant enzyme (total superoxide dismutase) activity was higher in the nebulized hydrogen-rich water treatment group compared with the blast injury control group (P < .01).

CONCLUSION

Hydrogen-rich water treatment significantly improves survival rates and lung function and reduces inflammation and oxidative stress in mice with primary blast lung injury. These findings suggest that hydrogen's antioxidant and anti-inflammatory properties play a crucial role in mitigating lung damage and improving respiratory function postinjury. Further long-term studies and imaging analyses are needed to confirm these findings and elucidate the molecular mechanisms involved. This study provides a theoretical basis for the clinical application of hydrogen-rich water in treating blast-induced lung injuries.