| Online-Ressource |
Verfasst von: | Korff, Sebastian [VerfasserIn]  |
| Loughran, Patricia [VerfasserIn]  |
| Cai, Chanchun [VerfasserIn]  |
| Lee, Yi Shan [VerfasserIn]  |
| Scott, Melanie [VerfasserIn]  |
| Billiar, Timothy R. [VerfasserIn]  |
Titel: | Eritoran attenuates tissue damage and inflammation in hemorrhagic shock/trauma |
Verf.angabe: | Sebastian Korff, Patricia Loughran, Chanchun Cai, Yi Shan Lee, Melanie Scott, and Timothy R. Billiar, MD |
E-Jahr: | 2013 |
Jahr: | 27 March 2013 |
Umfang: | 9 S. |
Fussnoten: | Gesehen am 01.12.2021 |
Titel Quelle: | Enthalten in: Journal of surgical research |
Ort Quelle: | Orlando, Fla. : Academic Press, 1961 |
Jahr Quelle: | 2013 |
Band/Heft Quelle: | 184(2013), 2, Seite e17-e25 |
ISSN Quelle: | 1095-8673 |
Abstract: | Background - Severe injury and associated hemorrhagic shock lead to an inflammatory response and subsequent increased tissue damage. Numerous reports have shown that injury-induced inflammation and the associated end-organ damage is driven by Toll-like receptor 4 (TLR4) activation via damage-associated molecular patterns. We examined the effectiveness of Eritoran tetrasodium (E5564), an inhibitor of TLR4 function, in reducing inflammation induced during hemorrhagic shock with resuscitation (HS/R) or after peripheral tissue injury (bilateral femur fracture, BFF). - Material and methods - Mice underwent HS/R or BFF with or without injection of Eritoran (5 mg/kg body weight) or vehicle control given before, both before and after, or only after HS/R or BFF. Mice were sacrificed after 6 h and plasma and tissue cytokines, liver damage (histology; aspartate aminotransferase/alanine aminotransferase), and inflammation (NF-κB) and gut permeability were assessed. - Results - In HS/R Eritoran significantly reduced liver damage (values ± SEM: alanine aminotransferase 9910 ± 3680 U/L versus 1239 ± 327 U/L and aspartate aminotransferase 5863 ± 2000 U/L versus 1246 ± 243 U/L, P < 0.01) at 6 h compared with control when given just before HS and again just prior to resuscitation. Eritoran administration also led to lower IL-6 levels in plasma and liver and less NF-κB activation in liver. Increases in gut barrier permeability induced by HS/R were also prevented with Eritoran. Eritoran similarly diminished BFF-mediated systemic inflammatory responses. - Conclusion - These data suggest Eritoran can inhibit tissue damage and inflammation induced via TLR4/myeloid differentiation factor 2 signaling from damage-associated molecular patterns released during HS/R or BFF. Eritoran may represent a promising therapeutic for trauma patients to prevent multiple organ failure. |
DOI: | doi:10.1016/j.jss.2013.03.023 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.jss.2013.03.023 |
| Volltext: https://www.sciencedirect.com/science/article/pii/S0022480413002187 |
| DOI: https://doi.org/10.1016/j.jss.2013.03.023 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | DAMPs |
| Liver |
| Mice |
| Organ damage |
| Tight junctions |
| Toll-like receptor |
K10plus-PPN: | 1752411919 |
Verknüpfungen: | → Zeitschrift |
Eritoran attenuates tissue damage and inflammation in hemorrhagic shock/trauma / Korff, Sebastian [VerfasserIn]; 27 March 2013 (Online-Ressource)