Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-κB and HMGB1

Relja, Borna; Wagner, Nils; Franz, Niklas; Dieteren, Scott; Mörs, Katharina; Schmidt, Julia; Marzi, Ingo; Perl, Mario

doi:10.1016/j.imbio.2017.10.037

Cited by 16 publications

(20 citation statements)

References 44 publications

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“…In the present study, resuscitation with EtP reduced the expression of CD11b on circulating neutrophils, indicating at an anti-inflammatory effect via inhibition of systemic activation of leukocytes. Intriguing data have been found after resuscitation with EtP which further reduced caspase-3/7 activity in circulating granulocytes, effects that can be associated with diminished tissue damage in liver and lung as shown in our previous studies ( 32 , 37 ). This is in contrast to above described findings, where tissue-protective effects were demonstrated by restoring apoptotic capacity in neutrophils.…”

Section: Discussionsupporting

confidence: 78%

“…No tissue damage or necrosis were observed in the sham group. The representative and detailed analyses of the local effects of a EtP-reperfusion on lungs and liver in the underlying model of TxT and H/R are shown in our referred studies ( 32 , 37 ).…”

Section: Resultsmentioning

confidence: 99%

“…Then, the samples were embedded in paraffin and subsequently sectioned and stained with hematoxylin-eosin (H&E). The histological examination of the tissue morphology in both organs was performed by an independent pathologist who allocated the H&E-stained sections to the different experimental groups in a blinded manner as described before ( 32 , 37 ).…”

Section: Methodsmentioning

confidence: 99%

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Ethyl Pyruvate Reduces Systemic Leukocyte Activation via Caspase-1 and NF-κB After Blunt Chest Trauma and Haemorrhagic Shock

et al. 2020

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Background: Blunt chest (thoracic) trauma (TxT) and haemorrhagic shock with subsequent resuscitation (H/R) induce strong systemic and local inflammatory response, which is closely associated with apoptotic cell loss and subsequently impaired organ function. The underlying mechanisms are not completely understood, therefore, the treatment of patients suffering from TxT+H/R is challenging. In our recent studies, we have demonstrated local anti-inflammatory effects of ethyl pyruvate (EtP) in lung and liver after TxT+H/R. Here, the therapeutic potential of a reperfusion regime with EtP on the early post-traumatic systemic inflammatory response and apoptotic changes after TxT followed by H/R were investigated. Methods: Female Lewis rats underwent TxT followed by haemorrhagic shock (60 min). Resuscitation was performed with own blood transfusion and either lactated Ringers solution (LR) or LR supplemented with EtP (50 mg/kg). Sham group underwent the surgical procedures. After 2 h blood as well as lung and liver tissues were obtained for analyses. Systemic activation of neutrophils (expression of CD11b and CD62L), leukocyte phagocytosis, apoptosis (caspase-3/7 activation), pyroptosis (caspase-1 activation) and NF-κB p65 activity were assessed. p < 0.05 was considered significant. Results: TxT+H/R-induced systemic activation of neutrophils (increased CD11b and reduced CD62L expression) was significantly reduced by EtP. Trauma-induced delayed neutrophil apoptosis was further reduced by EtP reperfusion but remained unaltered in monocytes. Reperfusion with EtP significantly increased the phagocytizing capacity of granulocytes. Trauma-induced inflammasome activation, which was observed in monocytes and not in neutrophils, was significantly reduced by EtP in both cell entities. NF-κB p65 activation, which was increased in neutrophils and monocytes was significantly decreased in monocytes. Conclusion: TxT+H/R-induced systemic activation of both neutrophils and monocytes concomitant with increased systemic inflammation was reduced by a reperfusion with EtP and was associated with a down-regulation of NF-κB p65 activation.

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Section: Discussionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Ethyl Pyruvate Reduces Systemic Leukocyte Activation via Caspase-1 and NF-κB After Blunt Chest Trauma and Haemorrhagic Shock

et al. 2020

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“…There are other models of chest trauma e.g. providing a blast wave to the thorax 33,50 . The microscopic evaluation of lung samples revealed severe intraalveolar, intrabronchial, and subpleural hemorrhage as well as interstitial edema and atelectasis 33 .…”

Section: Discussionmentioning

confidence: 99%

Traumatic injury pattern is of equal relevance as injury severity for experimental (poly)trauma modeling

Yang

Bundkirchen

Krettek

et al. 2019

Sci Rep

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This study aims to elaborate the relevance of trauma severity and traumatic injury pattern in different multiple and/or polytrauma models by comparing five singular trauma to two different polytrauma (PT) models with high and one multiple trauma (MT) model with low injury-severity score (ISS). The aim is to provide a baseline for reducing animal harm according to 3Rs by providing less injury as possible in polytrauma modeling. Mice were randomly assigned to 10 groups: controls (Ctrl; n = 15), Sham (n = 15); monotrauma groups: hemorrhagic shock (HS; n = 15), thoracic trauma (TxT; n = 18), osteotomy with external fixation (Fx; n = 16), bilateral soft tissue trauma (bSTT; n = 16) or laparotomy (Lap; n = 16); two PT groups: PT I (TxT + HS + Fx; ISS = 18; n = 18), PT II (TxT + HS + Fx + Lap; ISS = 22; n = 18), and a MT group (TxT + HS + bSTT + Lap, ISS = 13; n = 18). Activity and mortality were assessed. Blood gas analyses and organ damage markers were determined after 6 h. Significant mortality occurred in TxT, PT and MT (11.7%). Activity decreased significantly in TxT, HS, both polytrauma and MT vs . Ctrl/Sham. PT-groups and MT had significantly decreased activity vs . bsTT, Lap or Fx. MT had significantly lower pCO 2 vs . Ctrl/Sham, Lap or bsTT. Transaminases increased significantly in PT-groups and MT vs . Ctrl, Sham or monotrauma. Traumatic injury pattern is of comparable relevance as injury severity for experimental multiple or (poly)trauma modeling.

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“…It has been documented that the HMGB1 inhibitor glycyrrhizic acid can mediate renal injury and inflammatory responses in diabetic rats by regulating the activation of the RAGE/TLR4-related ERK and p38 MAPK/NF-κB signaling pathways [ 25 ]. Ethyl pyruvate can suppress acute lung damage through inhibition of NF-κB and HMGB1 following trauma and hemorrhagic shock [ 26 ]. Thus, we speculate that HMGB1 may be useful as a valid therapeutic target for controlling H. parasuis infection.…”

Section: Introductionmentioning

confidence: 99%

Baicalin Inhibits Haemophilus Parasuis-Induced High-Mobility Group Box 1 Release during Inflammation

Liu

Xiao

et al. 2018

IJMS

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Haemophilus parasuis (H. parasuis) can cause Glässer’s disease in pigs. However, the molecular mechanism of the inflammation response induced by H. parasuis remains unclear. The high-mobility group box 1 (HMGB1) protein is related to the pathogenesis of various infectious pathogens, but little is known about whether H. parasuis can induce the release of HMGB1 in piglet peripheral blood monocytes. Baicalin displays important anti-inflammatory and anti-microbial activities. In the present study, we investigated whether H. parasuis can trigger the secretion of HMGB1 in piglet peripheral blood monocytes and the anti-inflammatory effect of baicalin on the production of HMGB1 in peripheral blood monocytes induced by H. parasuis during the inflammation response. In addition, host cell responses stimulated by H. parasuis were determined with RNA-Seq. The RNA-Seq results showed that H. parasuis infection provokes the expression of cytokines and the activation of numerous pathways. In addition, baicalin significantly reduced the release of HMGB1 in peripheral blood monocytes induced by H. parasuis. Taken together, our study showed that H. parasuis can induce the release of HMGB1 and baicalin can inhibit HMGB1 secretion in an H. parasuis-induced peripheral blood monocytes model, which may provide a new strategy for preventing the inflammatory disorders induced by H. parasuis.

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Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-κB and HMGB1

Cited by 16 publications

References 44 publications

Ethyl Pyruvate Reduces Systemic Leukocyte Activation via Caspase-1 and NF-κB After Blunt Chest Trauma and Haemorrhagic Shock

Ethyl Pyruvate Reduces Systemic Leukocyte Activation via Caspase-1 and NF-κB After Blunt Chest Trauma and Haemorrhagic Shock

Traumatic injury pattern is of equal relevance as injury severity for experimental (poly)trauma modeling

Baicalin Inhibits Haemophilus Parasuis-Induced High-Mobility Group Box 1 Release during Inflammation

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