Cell-free DNA as a potential marker to predict carbon tetrachloride-induced acute liver injury in rats

Benjamin Fredrick Gruenbaum, Matthew Boyko, Bertha Delgado, Amos Douvdevany, Shaun Evan Gruenbaum, Israel Melamed, Micky Gideon, Evaldas Cesnulis, Yoram Shapira, Alexander Zlotnik

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Purpose: 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.

Original languageEnglish
Pages (from-to)721-727
Number of pages7
JournalHepatology International
Issue number2
StatePublished - 1 Jun 2013


  • Biomarker
  • Cell-free DNA
  • Hepatic injury
  • Liver damage

ASJC Scopus subject areas

  • Hepatology


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