PROTECTIVE EFFECTS OF HYDROGEN GAS ON MURINE POLYMICROBIAL SEPSIS VIA REDUCING OXIDATIVE STRESS AND HMGB1 RELEASE

Despite recent advances in antibiotic therapy and intensive care, sepsis is still considered to be the most common cause of death in intensive care units. Excessive production of reactive oxygen species plays an important role in the pathogenesis of sepsis. Recently, it has been suggested that molecular hydrogen (H-2) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radicals (center dot OH, the most cytotoxic reactive oxygen species) and effectively protects against organ damage induced by I/R. Therefore, we hypothesized that H-2 treatment had a beneficial effect on sepsis. In the present study, we found that H-2 inhalation starting at 1 and 6 h after cecal ligation and puncture (CLP) or sham operation significantly improved the survival rate of septic mice with moderate or severe CLP in a concentration-and time-dependent manner. Furthermore, moderate or severe CLP mice showed significant multiple organ damage characterized by the increases of lung myeloperoxidase activity, wet-to-dry weight ratio, protein concentration in bronchoalveolar lavage, serum biochemical parameters, and organ histopathologic scores at 24 h after CLP operation, which was significantly attenuated by 2% H-2 treatment. In addition, we found that the beneficial effects of H-2 treatment on sepsis and sepsis-associated organ damage were associated with the decreased levels of oxidative product, increased activities of antioxidant enzymes, and reduced levels of high-mobility group box 1 in serum and tissue. Thus, H-2 inhalation may be an effective therapeutic strategy for patients with sepsis.