Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-kappa B and HMGB1
Relja B, Wagner N, Franz N, Dieteren S, Moers K, Schmidt J, Marzi I, Perl M (2018)
Publication Status: Published
Publication Type: Journal article
Publication year: 2018
Journal
Publisher: ELSEVIER GMBH, URBAN & FISCHER VERLAG
Book Volume: 223
Pages Range: 310-318
Journal Issue: 3
DOI: 10.1016/j.imbio.2017.10.037
Abstract
Objective: After blunt thoracic trauma (TxT) and hemorrhagic shock with resuscitation (H/R) intense local inflammatory response and cell loss frequently impair the pulmonary function. Ethyl pyruvate (EP) has been reported to improve the pathophysiologic derangements in models of acute inflammation. Here, we studied the effects of EP on inflammation and lung damage after TxT + H/R.Methods: Twenty four female Lewis rats (180-240 g) were randomly divided into 3 groups: two groups underwent TxT followed by hemorrhagic shock (35 +/- 3 mmHg) for 60 min and resuscitation with either Ringers-Lactat (RL) alone or RL supplemented with EP (EP, 50 mg/kg). Sham operated animals underwent surgical procedures. Two hours later bronchoalveolar lavage fluid (BAL), lung tissue and blood were collected for analyses.Results: EP significantly improved pO(2) levels compared to RL after TxT + H/R. TxT + H/R induced elevated levels of lactate dehydrogenase, total protein concentration in BAL and lung damage as evidenced by lung histology; these effects were significantly reduced by EP. Local inflammatory markers, lung TNF-alpha protein levels and infiltration with polymorphonuclear leukocytes (PMNL) significantly decreased in EP vs. RL group after TxT + H/R. Indicators of apoptosis as reduced BCL-2 and increased FAS gene expression after TxT + H/R were significantly increased or decreased, respectively, by EP after TxT + H/R. EP reduced TxT + H/R-induced p65 phosphorylation, which was concomitant with reduced HMGB1 levels in lung sections.Conclusions: Taken together, TxT + H/R induced strong inflammatory response and apoptotic changes as well as lung injury which were markedly diminished by EP. Our results suggest that this might be mediated via NF-kappa B and/or HMGB1 dependent mechanism.
Authors with CRIS profile
Involved external institutions
Goethe-Universität Frankfurt am Main
Germany (DE)
Berufsgenossenschaftliche Unfallklinik (BGU) Murnau
Germany (DE)
Germany (DE)
Berufsgenossenschaftliche Unfallklinik (BGU) Murnau
Germany (DE)
How to cite
APA:
Relja, B., Wagner, N., Franz, N., Dieteren, S., Moers, K., Schmidt, J.,... Perl, M. (2018). Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-kappa B and HMGB1. Immunobiology, 223(3), 310-318. https://doi.org/10.1016/j.imbio.2017.10.037
MLA:
Relja, Borna, et al. "Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-kappa B and HMGB1." Immunobiology 223.3 (2018): 310-318.
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