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

• Published in: International immunopharmacology Vol. 69; pp. 11 - 18
• Main Authors: Yu, Yang, Yang, Yongyan, Yang, Man, Wang, Chunyan, Xie, Keliang, Yu, Yonghao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2019; Elsevier BV
• Subjects: Animal models; Animal tissues; Antioxidants; Apoptosis; Catalase; Cecum; Cytokines; Enzyme-linked immunosorbent assay; Enzymes; Heme; HMGB1 protein; Hydrogen gas; Inflammation; Inhalation; Injuries; Interleukin 10; Interleukin 6; Lung injury; Lungs; Malondialdehyde; Mice; Nrf2 knockout mice; Oxidative stress; Oxygenase; Respiration; Rodents; Sepsis; Superoxide dismutase; Surgery; Survival; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Weight; Sepsis; Nrf2 knockout mice; Hydrogen gas; Lung injury
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.01.022

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. 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). 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. •H2 protects against sepsis-induced lung injury in vivo.•H2 can ameliorate lung injuries through the regulation of HO-1 and HMGB1 release.•Nrf2 plays a key role in the protective effects of H2 against sepsis-induced lung injury.