Effects of posttreatment with propofol on mortality and cytokine responses to endotoxin-induced shock in rats*

Taniguchi, Tadatsugu; Kanakura, Hiroko; Yamamoto, Ken

doi:10.1097/00003246-200204000-00032

Cited by 79 publications

(56 citation statements)

References 10 publications

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“…The increase in TNF-α may be an adaptive response of a jeopardized myocardium [18] . Low-and high-dose propofol (1 and 10 mg·kg -1 ·h -1 , respectively) exert beneficial effects on septic shock in rats and reduce serum TNF-α and IL-10 production after sepsis [19] . The difference between the results obtained here and these previous reports may be due to the administration of a long-term high-dose propofol infusion in this study; the use of high doses of propofol for prolonged periods is generally linked to a decrease in performance [3,15,17] .…”

Section: Discussionmentioning

confidence: 99%

Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation

et al. 2011

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Aim: To explore the mechanisms underlying the propofol infusion syndrome (PRIS), a potentially fatal complication during prolonged propofol infusion. Methods: Male rabbits under mechanical ventilation through endotracheal intubation were divided into 3 groups (n=6 for each) that were sedated with 1% propofol (Group P), isoflurane (Group I) or isoflurane while receiving 10% intralipid (Group II), respectively. Blood biochemical parameters were collected at 0, 6, 12, 18, 24, and 30-36 h after the initiation of treatments. The hearts were removed out immediately after the experiments, and the level of tumor necrosis factor (TNF)-α in the hearts were studied using immunohistochemistry. AMP-activated protein kinase (AMPK) and phospho-AMPK in the hearts were assessed using Western blotting. Results: The mortality rate was 50% in Group P, and 0% in Groups I and II. The serum lipids and liver function indices in Group P were significantly increased, but moderately increased in Group II. Significant decreases in these indices were found in Groups I. All the groups showed dramatically increased release of creatine kinase (CK). Intense positive staining of TNF-α was found in all the heart samples in Group P, but only weak and neglectful staining was found in the hearts from Group II and Group I, respectively. AMPK phosphorylation was significantly increased in the hearts of Group P. Conclusion: Continuous infusion of large dose of propofol in rabbits undergoing prolonged mechanical ventilation causes hyperlipidemia, liver dysfunction, increased CK levels, AMPK activation and myocardial injury. The imbalance between energy demand and utilization may contribute to PRIS.

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Section: Discussionmentioning

confidence: 99%

Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation

et al. 2011

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“…To our knowledge, our study shows, for the first time, that, at therapeutic concentrations, propofol inhibits the respiratory burst, degranulation, and chemotaxis of fMLF-activated neutrophils by competitively binding to FPR1 and thus attenuating downstream signaling, including in the Ca 2+ , AKT, and ERK1/2 pathways. There is considerable evidence from clinical and experimental studies that propofol exerts significant protective effects against inflammatory and cardiovascular diseases, inhibiting the production of cytokines and the clearance of ROS (3,30). Propofol has been shown to reduce oxidative injury to organ in endotoxemia animals (31) and in patients undergoing cardiac surgery (32).…”

Section: Discussionmentioning

confidence: 99%

“…As well as its anesthetic effects, there is growing evidence in animal and human studies that propofol exerts protective effects during acute inflammatory processes (1). In animal studies, propofol has decreased cytokine release during sepsis (2,3) and reduced neutrophil-mediated inflammation in acute pulmonary injury (4,5). In human studies, propofol has attenuated myocardial reperfusion injury and pulmonary dysfunction following cardiopulmonary bypass by reducing free radical release and modulating the inflammatory process (6,7).…”

mentioning

confidence: 99%

Propofol Inhibits Superoxide Production, Elastase Release, and Chemotaxis in Formyl Peptide–Activated Human Neutrophils by Blocking Formyl Peptide Receptor 1

Yang

Chung

et al. 2013

The Journal of Immunology

174

200

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Neutrophils play a critical role in acute and chronic inflammatory processes, including myocardial ischemia/reperfusion injury, sepsis, and adult respiratory distress syndrome. Binding of formyl peptide receptor 1 (FPR1) by N-formyl peptides can activate neutrophils and may represent a new therapeutic target in either sterile or septic inflammation. Propofol, a widely used i.v. anesthetic, has been shown to modulate immunoinflammatory responses. However, the mechanism of propofol remains to be established. In this study, we showed that propofol significantly reduced superoxide generation, elastase release, and chemotaxis in human neutrophils activated by fMLF. Propofol did not alter superoxide generation or elastase release in a cell-free system. Neither inhibitors of γ-aminobutyric acid receptors nor an inhibitor of protein kinase A reversed the inhibitory effects of propofol. In addition, propofol showed less inhibitory effects in non-FPR1–induced cell responses. The signaling pathways downstream from FPR1, involving calcium, AKT, and ERK1/2, were also competitively inhibited by propofol. These results show that propofol selectively and competitively inhibits the FPR1-induced human neutrophil activation. Consistent with the hypothesis, propofol inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analog of fMLF, to FPR1 in human neutrophils, differentiated THP-1 cells, and FPR1-transfected human embryonic kidney-293 cells. To our knowledge, our results identify, for the first time, a novel anti-inflammatory mechanism of propofol by competitively blocking FPR1 in human neutrophils. Considering the importance of N-formyl peptides in inflammatory processes, our data indicate that propofol may have therapeutic potential to attenuate neutrophil-mediated inflammatory diseases by blocking FPR1.

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“…In recent years, the antiinflammatory effects of propofol have been demonstrated in vitro and in vivo [10][11][12]. It is reported that after endotoxin injection, propofol treatment may reduce the production of inflammatory cytokines and the mortality rate in rats experiencing endotoxic shock [13]. Also, our previous work has shown that propofol can protect endothelial cells against lipopolysaccharide (LPS)-induced barrier dysfunction [14].…”

Section: Introductionmentioning

confidence: 99%

Early administration of propofol protects against endotoxin-induced acute lung injury in rats by inhibiting the TGF-β1-Smad2 dependent pathway

et al. 2009

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Effects of posttreatment with propofol on mortality and cytokine responses to endotoxin-induced shock in rats*

Cited by 79 publications

References 10 publications

Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation

Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation

Propofol Inhibits Superoxide Production, Elastase Release, and Chemotaxis in Formyl Peptide–Activated Human Neutrophils by Blocking Formyl Peptide Receptor 1

Early administration of propofol protects against endotoxin-induced acute lung injury in rats by inhibiting the TGF-β1-Smad2 dependent pathway

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