Prevention of hemorrhagic shock-induced lung injury by heme arginate treatment in rats

Maeshima, Kyoichiro; Takahashi, Toru; Uehara, Kenji; Shimizu, Hiroko; Omori, Emiko; Yokoyama, Masataka; Tani, Toru; Akagi, Reiko; Morita, Kiyoshi

doi:10.1016/j.bcp.2005.03.007

Cited by 44 publications

(49 citation statements)

References 56 publications

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“…For immunofluorescent analysis, anti-HO-1 (Abcam, Cambridge, MA) and anti-aquaporin-5 (EMD Chemicals, Gibbstown, NJ) were used. For immunohistological staining, anti-HO-1 polyclonal antibody (Enzo Life Sciences, Farmingdale, NY), anti-cleaved caspase 3 polyclonal antibody (Cell Signaling Technology, Danvers, MA), and anti-8-hydroxy-2=-deoxyguanosine (8-OHdG) monoclonal antibody (NIKKEN SEIL, Shizuoka, Japan) were used, as described previously (29,34,45).…”

Section: Animalsmentioning

confidence: 99%

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

Kawamura

Wakabayashi

Shigemura

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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146

113

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lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine. Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to four experimental groups and administered the following gas mixtures for 60 h: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice. Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen.

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Section: Animalsmentioning

confidence: 99%

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

Kawamura

Wakabayashi

Shigemura

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

146

113

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“…We previously reported that the HO-1 mRNA level increased markedly following HSR in the rat kidney (6). Thus, we examined the effect of HSR on HO-1 protein expression in the kidney by fluorescent immunohistochemical analysis and by measuring HO activity 12 h after HSR.…”

Section: Ho-1 Protein Expressionmentioning

confidence: 98%

“…Rats were anesthetized with intraperitoneal sodium pentobarbital (50 mg/kg) and subjected to sham or HSR, as described previously (6,10,11). In brief, the left femoral artery and vein were dissected using aseptic techniques and cannulated with a heparinized polyethylene tube.…”

Section: Animalsmentioning

confidence: 99%

“…Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress that leads to multiple organ damage (3,4), and the kidney is one of the target organs of HSR-mediated oxidative tissue injury (5). We previously reported that HO-1 mRNA was highly induced in the kidney after HSR in a rat model of HSR (6). However, the role of renal HO-1 induction following HSR remains elusive.…”

Section: Introductionmentioning

confidence: 99%

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Role of heme oxygenase-1 in protection of the kidney after hemorrhagic shock

et al. 2010

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Abstract. Hemorrhagic shock followed by resuscitation (HSR) causes oxidative stress, which results in multiple organ damage. The kidney is one of the target organs of HSR-mediated oxidative tissue injury. Heme oxygenase (HO)-1, the rate-limiting enzyme in heme catabolism, is induced by oxidative stress; it protects against oxidative tissue injuries. The aim of the present study was to examine the role of renal HO-1 induction after HSR. Rats were subjected to hemorrhagic shock to achieve a mean arterial pressure of 30 mmHg for 60 min, followed by resuscitation with the shed blood. HSR resulted in a significant increase in functional HO-1 protein in the tubular epithelial cells of the kidney, whereas HSR resulted in only a slight increase in gene expression of tumor necrosis factor (TNF)-· and inducible nitric oxide synthase (iNOS), and in protein expression of activated caspase-3 solely in renal cells where HO-1 expression was absent. HSR also resulted in a significant increase in Bcl-2 gene expression. Pretreatment of HSR animals with tinmesoporphyrin (0.5 μmol/kg), a specific competitive inhibitor of HO activity, resulted in a significant decrease in HO activity and exacerbated tissue inflammation and apoptotic cell death as judged by the marked increase in expression of TNF-· and iNOS, and in activated caspase-3-positive cells, and the significant reduction in Bcl-2 expression, respectively. These findings indicate that HO-1 induction is an adaptive response to HSR-induced oxidative stress and is essential for protecting tubular epithelial cells from oxidative damage through its anti-inflammatory and anti-apoptotic properties.

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“…LPS also induces hepatic injury as revealed by increases in serum ALT and aspartate transaminase (AST) activities, TNF-mRNA, iNOS mRNA, and DNAbinding activity of NF-κB, and extensive hepatocyte necrosis. However, induction of HO-1 by rhIL-11 ameliorated the LPS-induced hepatic injury and decreased LPS-induced mortality (Maeshima et al, 2004) In an animal model, the cytoprotective effects of HO-1 against oxidative stress were also shown in other organs (Maeshima et al, 2005, Barreiro et al, 2002, Shimizu et al, 2000, Poole et al, 2005, Yu et al, 2009). …”

Section: Animal Studiesmentioning

confidence: 99%