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

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Abstract

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.

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Authors and Affiliations

  1. 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

    Benjamin Fredrick Gruenbaum, Matthew Boyko, Yoram Shapira & Alexander Zlotnik

  2. Department of Pathology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Bertha Delgado

  3. Department of Clinical Biochemistry, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Amos Douvdevany

  4. Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA

    Shaun Evan Gruenbaum

  5. Department of Neurosurgery, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Israel Melamed & Micky Gideon

  6. Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland

    Evaldas Cesnulis

Authors
  1. Benjamin Fredrick Gruenbaum
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  2. Matthew Boyko
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  3. Bertha Delgado
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  4. Amos Douvdevany
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  5. Shaun Evan Gruenbaum
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  6. Israel Melamed
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  9. Yoram Shapira
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  10. Alexander Zlotnik
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Correspondence to Alexander Zlotnik.

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Gruenbaum, B.F., Boyko, M., Delgado, B. et al. Cell-free DNA as a potential marker to predict carbon tetrachloride-induced acute liver injury in rats. Hepatol Int 7, 721–727 (2013). https://doi.org/10.1007/s12072-012-9414-z

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  • DOI: https://doi.org/10.1007/s12072-012-9414-z

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