Protective effects of early treatment with propofol on endotoxin-induced acute lung injury in rats

Gao, Ju; Zeng, Bingjie; Zhou, Liang; Yuan, Shiying

doi:10.1093/bja/aeh050

Cited by 58 publications

(39 citation statements)

References 8 publications

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“…Loss of pulmonary barrier function is commonly seen as one of the most important features of ALI [32,33,34,35,36,37,38,39,40,41]. Numerous studies showed that indirect lung injury leading to ALI is commonly caused by extrapulmonary foci such as peritonitis, pancreatitis, trauma, massive transfusions or major surgery [18,19,20,21].…”

Section: Discussionmentioning

confidence: 99%

Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release

et al. 2008

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Background: Resident tissue macrophages exert important functions during severe systemic infection and contribute to changes in local as well as systemic immune responses. Alveolar macrophages (AM) play a crucial role in airway diseases and in the defense against microorganisms invading the body via the bronchopulmonary tract. It has been postulated that AM are involved in the development of acute local disorders as a consequence of extrapulmonary stimuli like pancreatitis, peritonitis, or trauma. Objective: The aim of this study was to analyze the local and systemic role of AM during sepsis using selective AM depletion in the murine colon ascendens stent peritonitis (CASP) model of polymicrobial sepsis. Methods: 48 h prior to CASP surgery, AM of female C57BL/6 mice were selectively depleted by intratracheal application of clodronate liposomes (Lipo-clod). For control purposes, phosphate-buffered saline (PBS) liposomes (Lipo-PBS) were used. Results: CASP led to significantly elevated levels of local and systemic cytokines independent of the presence of AM. In contrast, levels of gut-derived bacteria in bronchoalveolar lavage and lung of septic mice were significantly higher in Lipo-clod-treated animals compared to Lipo-PBS-treated animals. After CASP-induced sepsis, local barrier dysfunction in the lung was detected; AM depletion resulted in severely enhanced development of acute lung injury. Consequently, Lipo-clod-treated animals showed strongly reduced survival rates after CASP. Conclusions: Contrarily to other macrophage populations, AM do not significantly contribute to local and systemic cytokine release during polymicrobial abdominal sepsis. AM have important protective functions for local clearance of gut-derived bacteria and attenuation of lung injury.

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Section: Discussionmentioning

confidence: 99%

Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release

et al. 2008

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“…This dosage of LPS was used in our previous studies 26 and by others. 27,28 At different time points (0, 2, 4, 8, and 12 h (n ¼ 7)), the animals were killed; blood and liver tissue were taken for analytical examination. All animals received humane care according to the criteria outlined in the 'Guide for the Care and Use of Laboratory Animals' prepared by the National Academy of Sciences and published by the National Institutes of Health (NIH publication 86-23 revised 1985).…”

Section: Materials and Methods Endotoxic Shockmentioning

confidence: 99%

A novel endotoxin-induced pathway: upregulation of heme oxygenase 1, accumulation of free iron, and free iron-mediated mitochondrial dysfunction

Duvigneau

Piskernik

Haindl

et al. 2008

Laboratory Investigation

100

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Mitochondria are involved in the development of organ failure in critical care diseases. However, the mechanisms underlying mitochondrial dysfunction are not clear yet. Inducible hemoxygenase (HO-1), a member of the heat shock protein family, is upregulated in critical care diseases and considered to confer cytoprotection against oxidative stress. However, one of the products of HO-1 is Fe 2 þ which multiplies the damaging potential of reactive oxygen species catalyzing Fenton reaction. The aim of this study was to clarify the relevance of free iron metabolism to the oxidative damage of the liver in endotoxic shock and its impact on mitochondrial function. Endotoxic shock in rats was induced by injection of lipopolysaccharide (LPS) at a dose of 8 mg/kg (i.v.). We observed that the pro-inflammatory cytokine TNF-a and the liver necrosis marker aspartate aminotransferase were increased in blood, confirming inflammatory response to LPS and damage to liver tissue, respectively. The levels of free iron in the liver were significantly increased at 4 and 8 h after onset of endotoxic shock, which did not coincide with the decrease of transferrin iron levels in the blood, but rather with expression of the inducible form of heme oxygenase (HO-1). The proteins important for sequestering free iron (ferritin) and the export of iron out of the cells (ferroportin) were downregulated facilitating the accumulation of free iron in cells. The temporarily increased concentration of free iron in the liver correlated with the temporary impairment of both mitochondrial function and tissue ATP levels. Addition of exogenous iron ions to mitochondria isolated from control animals resulted in an impairment of mitochondrial respiration similar to that observed in endotoxic shock in vivo. Our data suggest that free iron released by HO-1 causes mitochondrial dysfunction in pathological situations accompanied by endotoxic shock.

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“…In studies on endothelial cells, propofol has been reported to protect endothelial cells against the toxicity of peroxynitrite [13]. Recently, our studies have also shown propofol signifi cantly reduced endotoxin-induced peroxynitrite, and provided protective effects on endotoxin-induced acute lung injury and microvascular permeability in rats [14].…”

Section: Introductionmentioning

confidence: 71%

“…Our previous studies revealed that, in an endotoxin model, propofol signifi cantly attenuated LPS-enhanced expression of lung peroxynitrite and iNOSmRNA [14]. Studies in vitro also have reported that propofol protects endothelial cells against the toxicity of peroxynitrite [22,23] and reduces peroxynitrite in bronchial cells exposed to NO [12].…”

Section: Discussionmentioning

confidence: 93%

Protective effects of propofol on lipopolysaccharide-activated endothelial cell barrier dysfunction

et al. 2006

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Protective effects of early treatment with propofol on endotoxin-induced acute lung injury in rats

Abstract: These findings indicate that early administration of propofol may provide protective effects against endotoxin-induced acute lung injury.

Cited by 58 publications

References 8 publications

Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release

Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release

A novel endotoxin-induced pathway: upregulation of heme oxygenase 1, accumulation of free iron, and free iron-mediated mitochondrial dysfunction

Protective effects of propofol on lipopolysaccharide-activated endothelial cell barrier dysfunction

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