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Li Y.,Tianjin Medical University | Li Y.,Tianjin Institute of Anesthesiology | Li Q.,Tianjin Peoples Hospital | Chen H.,Tianjin Medical University | And 11 more authors.
Shock | Year: 2015

Hydrogen gas (H2) has antioxidative, anti-inflammatory, and antiapoptotic effects and may have beneficial effects in severe sepsis. The purpose of this study was to investigate the mechanisms underlying these protective effects. Male Institute for Cancer Research mice were randomized into 6 groups: sham; sham + H2; severe sepsis; severe sepsis + H2; severe sepsis + zinc protoporphyrin IX (ZnPPIX), a heme oxygenase-1 (HO-1) inhibitor; and severe sepsis + H2 + ZnPPIX. Cecal ligation and puncture (CLP) was used to induce sepsis. Mice in the H2 groups received inhaled 2% H2 for 1 h at 1 h and 6 h after CLP or sham operation. Mice in the ZnPPIX groups received 40-mg/kg ZnPPIX by intraperitoneal injection 1 h before CLP. Tin protoporphyrin IX (TinPPIX), another HO-1 inhibitor, was also used in part for this study. Mice in the TinPPIX groups received 50-mg/kg TinPPIX through subcutaneous injection 6 h before CLP. The levels of biochemical markers, oxidative products, inflammatory mediator, the number of intestinal apoptotic cells, and the colony-forming unit numbers in the peritoneal lavage fluid were much higher in the severe sepsis group compared with the sham group. Intestinal injury in animals with severe sepsis was worse than that in animals in the sham group. H2 therapy in the animals with severe sepsis was associated with reduced intestinal injury, decreased numbers of colony-forming unit and apoptotic cells, reduced levels of biochemical markers, oxidative products, and high-mobility group box 1 protein. The protective effects of H2 were reversed by ZnPPIX and TinPPIX. Protein and messenger RNA expressions of HO-1 and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) in the intestine were increased in the severe sepsis group compared to the sham group, and H2 further increased their expressions in the severe septic mice. Zinc protoporphyrin IX and TinPPIX inhibited the expression of HO-1 protein. Hydrogen has the capacity to protect mice from organ injury in severe sepsis through a mechanism involving HO-1. Copyright © 2015 by the Shock Society.

Meng X.,Tianjin Hospital | Chen H.,Tianjin Medical University | Chen H.,Tianjin Institute of Anesthesiology | Wang G.,Tianjin Medical University | And 5 more authors.
Experimental and Therapeutic Medicine | Year: 2015

Hydrogen has been reported to exert a therapeutic effect in several diseases due to its antioxidative, antiinflam-matory and anti-apoptotic properties. The aim of the present study was to investigate whether hydrogen-rich saline treatment could attenuate ovarian damage induced by cisplatin. A total of 240 adult, virgin, female Sprague Dawley rats, weighing 180-220 g, were randomly divided into four groups (n=60 per group): Control (Con), control + hydrogen-rich saline (Con + H2), cisplatin-induced ovarian injury (OI) and cisplatin-induced ovarian injury + hydrogen-rich saline (OI + H2). Cisplatin was diluted in saline immediately before use. In the OI and OI + H2 groups, the rats were administered a dose of cisplatin on the 1st and 7th days. The rats in the Con + H2 and OI + H2 groups were intraperitoneally injected with hydrogen-rich saline (10ml/kg body weight) once a day over a 2-week period. On the 14th, 28th and 42nd days (T1, T2 and T3) after the cisplatin injection, femoral vein blood was collected. At the end of the experiment, ovarian homogenates were prepared, and the samples were used for estrogen (E2), follicle-stimulating hormone (FSH), superoxide dismutase (SOD), catalase (CAT) and malondial- dehyde (MDA) examination. In addition, rats (n=10 per group) were sacrificed for bilateral ovary removal; one was fixed in formalin for follicle-counting analysis, while the other was used for nuclear factor erythroid 2-related factor 2 (Nrf2) detection by western blotting. Hydrogen-rich saline attenuated the FSH release, elevated the level of E2, improved the development of follicles, and reduced the damage to the ovarian cortex at T1, T2 and T3 in the OI + H2 rats. Cisplatin induced oxidative stress by increasing the levels of oxidation products and attenuating the activity of antioxidant enzyme, which could be reversed by hydrogen-rich saline treatment. Furthermore, hydrogen-rich saline regulated the Nrf2 protein expression in rats with ovarian damage. In conclusion, hydrogen-rich saline exerts a protective effect against cisplatin-induced ovarian injury by reducing MDA and increasing SOD and CAT activity. Ovarian injury induced by chemotherapy involves the activation of Nrf2. © 2015, Spandidos Publications. All rights reserved.

Li Y.,Tianjin Medical University | Li Y.,Tianjin Institute of Anesthesiology | Xie K.,Tianjin Medical University | Xie K.,Tianjin Institute of Anesthesiology | And 6 more authors.
Journal of Surgical Research | Year: 2015

Background Sepsis is a potentially fatal whole-body inflammation caused by severe infection. Hydrogen gas (H2) is effective for treating sepsis. In this study, we hypothesized that the protective function of H2 in mice with septic lung injury occurred through the activation of heme oxygenase 1 (HO-1) and its upstream regulator nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). Materials and methods Male institute of cancer research mice were subjected to sepsis by cecal ligation and puncture (CLP) with the presence or absence of H2. Beginning at 1 and 6 h after CLP or sham operation, respectively, 2% H2 was inhaled for 1 h. We intraperitoneally injected the HO-1 inhibitor zinc protoporphyrin IX (40 mg/kg) 1 h before CLP. To assess the severity of septic lung injury, we observed the 7-d survival rate, wet/dry weight ratio of lung, lung histopathologic score, oxygenation index, and so forth. Serum and homogenates from the lung, liver, and kidney were acquired for measuring the levels of high-mobility group box 1 (HMGB1) at 6, 12, and 24 h after CLP or sham operation. Furthermore, the protein and messenger RNA expression of Nrf2, HO-1, and HMGB1 was measured at 6, 12, and 24 h. Results Septic mice had a lower survival rate and more severe lung injury compared with the sham group. However, therapy with H2 increased the survival rate and alleviated the severity of lung injury, reduced the HMGB1 level, and increased the HO-1 and Nrf2 levels in septic mice. Moreover, the HO-1 inhibitor zinc protoporphyrin IX significantly eliminated the protective effect of H2 on septic lung injury. Conclusions H2 plays a significant role in regulating the release of the inflammatory cytokine HMGB1 in septic mice, which is partially mediated through the activation of HO-1 as a downstream molecule of Nrf2. © 2015 Elsevier Inc.

Xie K.,Tianjin Medical University | Xie K.,Tianjin Institute of Anesthesiology | Liu L.,Tianjin Medical University | Liu L.,Tianjin Institute of Anesthesiology | And 4 more authors.
BioMed Research International | Year: 2014

Sepsis is characterized by a severe inflammatory response to infection. It remains a major cause of morbidity and mortality in critically ill patients despite developments in monitoring devices, diagnostic tools, and new therapeutic options. Recently, some studies have found that molecular hydrogen is a new therapeutic gas. Our studies have found that hydrogen gas can improve the survival and organ damage in mice and rats with cecal ligation and puncture, zymosan, and lipopolysaccharide-induced sepsis. The mechanisms are associated with the regulation of oxidative stress, inflammatory response, and apoptosis, which might be through NF-B and Nrf2/HO-1 signaling pathway. In this paper, we summarized the progress of hydrogen treatment in sepsis. © 2014 Keliang Xie et al.

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