Hydrogen gas reduces HMGB1 release in lung tissues of septic mice in an Nrf2/HO-1-dependent pathway

Chunyan Wang, Keliang Xie, Man Yang, Yang Yu, Yong-Hao Yu, Yongyan Yang

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DOI: 10.1016/j.intimp.2019.01.022 DOI is the universal ID for this study.

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Background: Lung injury is a vital contributor of mortality in septic patients. Our previous studies have found that molecular hydrogen (H2), which has anti-oxidant, anti-inflammatory, and anti-apoptosis effects, had a therapeutic effect on a septic animal model through increasing expression of nuclear factor-erythroid 2-related factor 2 (Nrf2). The aim of this research was to investigate the effects of 2% H2 gas inhalation on sepsis-induced lung injury and its underlying mechanisms.

Methods: Male wild-type (WT) and Nrf2-knockout (Nrf2-KO) ICR mice underwent sham or cecal ligation and puncture (CLP) operation. Two percent of H2 gas was inhaled for 60 min beginning at both 1 h and 6 h after sham or CLP surgery. To assess the severity of septic lung injury, the 7-day survival rate, wet/dry (W/D) weight ratio of lung tissue, lung histopathologic score, pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), high-mobility group box 1 (HMGB1)), anti-inflammatory cytokine (interleukin 10 (IL-10)), antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and heme oxygenase 1 (HO-1)), and an oxidative product (malondialdehyde (MDA)) were detected after sham or CLP operation. The histopathologic changes were observed in lung tissues by hematoxylin and eosin (HE) staining, and pro-inflammatory cytokines (TNF-α and IL-6), anti-inflammatory cytokine (IL-10), antioxidant enzymes (SOD and CAT), and MDA were detected in lung tissues by an enzyme-linked immunosorbent assay (ELISA).

Results: The results indicated that 2% H2 gas treatment increased the survival rates, decreased the W/D weight ratio and the lung injury score, alleviated the injuries caused by oxidative stress and inflammation, and induced HO-1 level but reduced HMGB1 level in WT but not Krf2-KO mice. These data reveal that H2 gas could suppress lung injury in septic mice through regulation of HO-1 and HMGB1 expression and that Nrf2 plays a main role in the protective effects of H2 gas on lung damage caused by sepsis.

Publish Year 2019
Country China
Rank Positive
Journal International Immunopharmacology
Primary Topic Lung
Secondary TopicSepsis
Model Mouse
Tertiary TopicLung Injury
Vehicle Gas
pH N/A
Application Inhalation