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

Abstract

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. 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 5ml/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 120h 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 120h following injection of 5ml/kg carbon tetrachloride in 18 additional rats and in 10 control rats. CFD levels in rats subjected to carbon tetrachloride-induced ALI were significantly increased in all blood samples starting at 12h after the induction of ALI (p<0.001), reaching peak levels at 24h. Blood GOT, GPT, and total bilirubin were elevated in all blood samples starting at 3h after the induction of ALI (p<0.0001), reaching peak levels by 48h. 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 24h after ALI. 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.