title: The salutary effects of diphenyldifluoroketone EF24 in liver of a rat hemorrhagic shock model.
abstract: BACKGROUND
  Liver is a target for injury in low flow states and it plays a central role in the progression of systemic failure associated with hemorrhagic shock. Pharmacologic support can help recover liver function even after it has suffered extensive damage during ischemia and reperfusion phases. In this work we assessed the efficacy of a diphenyldifluoroketone EF24, an IKKβ inhibitor, in controlling hepatic inflammatory signaling caused by hemorrhagic shock in a rat model.
  
  
  METHODS
  Sprague Dawley rats were bled to about 50% of blood volume. The hemorrhaged rats were treated with vehicle control or EF24 (0.4 mg/kg) after 1 h of hemorrhage without any accompanying resuscitation. The study was terminated after additional 5 h to excise liver tissue for biochemical analyses and histology.
  
  
  RESULTS
  EF24 treatment alleviated hemorrhagic shock-induced histologic injury in the liver and restored serum transaminases to normal levels. Hemorrhagic shock induced the circulating levels of CD163 (a marker for macrophage activation) and CINC (an IL-8 analog), as well as myeloperoxidase activity in liver tissue. These markers of inflammatory injury were reduced by EF24 treatment. EF24 treatment also suppressed the expression of the Toll-like receptor 4, phospho-p65/Rel A, and cyclooxygenase-2 in liver tissues, indicating that it suppressed inflammatory pathway. Moreover, it reduced the hemorrhagic shock-induced increase in the expression of high mobility group box-1 protein. The evidence for apoptosis after hemorrhagic shock was inconclusive.
  
  
  CONCLUSIONS
  Even in the absence of volume support, EF24 treatment suppresses pro-inflammatory signaling in liver tissue and improves liver functional markers in hemorrhagic shock.
authors: Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, 1110 North Stonewall Avenue, Oklahoma City, OK, 73117, USA. vivekyadav78@gmail.com.
authors: Vivek R
authors: VR
authors: Yadav
authors: Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, 1110 North Stonewall Avenue, Oklahoma City, OK, 73117, USA. alamdar-hussain@ouhsc.edu.
authors: Alamdar
authors: A
authors: Hussain
authors: Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, 1110 North Stonewall Avenue, Oklahoma City, OK, 73117, USA. jun-xie@ouhc.edu.
authors: Jun
authors: J
authors: Xie
authors: Department of Comparative Medicine, University of Oklahoma Health Science Center, 1110 North Stonewall Avenue, Oklahoma City, OK, USA. stanely-kosanke@ouhsc.edu.
authors: Stanley
authors: S
authors: Kosanke
authors: Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, 1110 North Stonewall Avenue, Oklahoma City, OK, 73117, USA. vibhudutta-awasthi@ouhsc.edu.
authors: Vibhudutta
authors: V
authors: Awasthi
mesh_terms: D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D015151:Immunoblotting; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects*; D010881:Piperidones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy*
chemical_list: C524042:3,5-bis(2-fluorobenzylidene)piperidin-4-one; D001597:Benzylidene Compounds; D010881:Piperidones
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