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Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release
Keliang Xie1, Yonghao Yu, Yuping Pei
1Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, P. R. China.
Abstract:
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 (H2) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radicals (*OH, the most cytotoxic reactive oxygen species) and effectively protects against organ damage induced by I/R. Therefore, we hypothesized that H2 treatment had a beneficial effect on sepsis. In the present study, we found that H2 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% H2 treatment. In addition, we found that the beneficial effects of H2 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, H2 inhalation may be an effective therapeutic strategy for patients with sepsis.
Insights
Hydrogen (H2) inhalation improved survival and reduced organ damage in mouse models of sepsis. This antioxidant therapy selectively targets harmful reactive oxygen species, offering a potential new treatment for sepsis patients.
Area of Science:
- Biomedical research
- Critical care medicine
- Oxidative stress biology
Background:
- Sepsis remains a leading cause of death in intensive care units, despite advances in treatment.
- Excessive reactive oxygen species (ROS) production is a key factor in sepsis pathogenesis.
- Molecular hydrogen (H2) shows therapeutic potential as an antioxidant, selectively reducing cytotoxic hydroxyl radicals.
Purpose of the Study:
- To investigate the therapeutic effects of hydrogen (H2) inhalation on sepsis and associated organ damage.
- To determine if H2 treatment can improve survival rates in a mouse model of sepsis.
Main Methods:
- Sepsis was induced in mice using cecal ligation and puncture (CLP) or a sham operation.
- Hydrogen (H2) inhalation was administered at different concentrations and time points post-CLP.
- Organ damage was assessed by measuring biochemical markers, enzyme activities, and histopathological changes.
Main Results:
- H2 inhalation significantly improved survival rates in septic mice in a concentration- and time-dependent manner.
- H2 treatment attenuated multiple organ damage, including lung injury and systemic inflammation.
- Beneficial effects were linked to reduced oxidative products, enhanced antioxidant enzyme activity, and decreased high-mobility group box 1 levels.
Conclusions:
- Hydrogen (H2) inhalation demonstrates significant therapeutic benefits in a mouse model of sepsis.
- H2 treatment effectively reduces sepsis-induced organ damage by mitigating oxidative stress and inflammation.
- H2 inhalation presents a promising, novel therapeutic strategy for managing sepsis.
