title: Cell-free DNA as a potential marker to predict carbon tetrachloride-induced acute liver injury in rats.
abstract: OBJECTIVE
  Finding an optimal biomarker for the noninvasive evaluation of acute liver injury (ALI) may be of great value in predicting clinical outcomes and investigating potential treatments. We investigated cell-free DNA (CFD) as a potential biomarker to predict carbon tetrachloride-induced ALI in rats.
  
  
  METHODS
  Forty-five Sprague-Dawley rats were randomly assigned to three groups. ALI was induced by carbon tetrachloride via a nasogastric tube at 1, 2.5, or 5 ml/kg of a 50 % solution. Fifteen additional rats underwent a sham procedure. Blood samples were drawn at time t which was 0 (baseline), 3, 6, 12, 24, 48, 72, 96, and 120 h for the measurements of CFD, glutamate-pyruvate transaminase (GPT), glutamate-oxaloacetate transaminase (GOT), and total bilirubin. Prothrombin time and histology were examined at 24 and 120 h following injection of 5 ml/kg carbon tetrachloride in 18 additional rats and in 10 control rats.
  
  
  RESULTS
  CFD levels in rats subjected to carbon tetrachloride-induced ALI were significantly increased in all blood samples starting at 12 h after the induction of ALI (p < 0.001), reaching peak levels at 24 h. Blood GOT, GPT, and total bilirubin were elevated in all blood samples starting at 3 h after the induction of ALI (p < 0.0001), reaching peak levels by 48 h. A positive correlation was demonstrated between CFD levels and GOT (R (2) = 0.92), GPT (R (2) = 0.92), and total bilirubin (R (2) = 0.76). CFD levels correlated with liver damage seen on histological examination, as well as predicted liver damage, at 24 h after ALI.
  
  
  CONCLUSIONS
  CFD may be a useful biomarker for the prediction and measurement of ALI. There is no evidence to suggest that CFD is superior to other available noninvasive biomarkers.
authors.affiliation: Department of Anesthesiology and Critical Care, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, Beer Sheva, 84105, Israel.
authors.forename: Benjamin Fredrick
authors.initials: BF
authors.lastname: Gruenbaum
authors.affiliation: Department of Anesthesiology and Critical Care, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, Beer Sheva, 84105, Israel.
authors.forename: Matthew
authors.initials: M
authors.lastname: Boyko
authors.affiliation: Department of Pathology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Bertha
authors.initials: B
authors.lastname: Delgado
authors.affiliation: Department of Clinical Biochemistry, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Amos
authors.initials: A
authors.lastname: Douvdevany
authors.affiliation: Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Shaun Evan
authors.initials: SE
authors.lastname: Gruenbaum
authors.affiliation: Department of Neurosurgery, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Israel
authors.initials: I
authors.lastname: Melamed
authors.affiliation: Department of Neurosurgery, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Micky
authors.initials: M
authors.lastname: Gideon
authors.affiliation: Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Evaldas
authors.initials: E
authors.lastname: Cesnulis
authors.affiliation: Department of Anesthesiology and Critical Care, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, Beer Sheva, 84105, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Shapira
authors.affiliation: Department of Anesthesiology and Critical Care, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, Beer Sheva, 84105, Israel. zlotnika@bgu.ac.il.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zlotnik
keywords: Biomarker; Cell-free DNA; Hepatic injury; Liver damage