Benjamin Fredrick Gruenbaum1, Matthew Boyko1, Bertha Delgado2, Amos Douvdevany3, Shaun Evan Gruenbaum4, Israel Melamed5, Micky Gideon5, Evaldas Cesnulis6, Yoram Shapira1, Alexander Zlotnik7. 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. 2. Department of Pathology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. 3. Department of Clinical Biochemistry, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. 4. Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA. 5. Department of Neurosurgery, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. 6. Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland. 7. 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.
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.
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.
Authors: Anna E Rutherford; Linda S Hynan; Carolina B S Borges; David G Forcione; Jason T Blackard; Wenyu Lin; April R Gorman; Obaid Shakil Shaikh; Adrian Reuben; Edwyn Harrison; K Rajender Reddy; William M Le; Raymond T Chung Journal: Clin Gastroenterol Hepatol Date: 2007-10-29 Impact factor: 11.382
Authors: Dmitry Frank; Shiri Savir; Benjamin F Gruenbaum; Israel Melamed; Julia Grinshpun; Ruslan Kuts; Boris Knyazer; Alexander Zlotnik; Max Vinokur; Matthew Boyko Journal: J Vis Exp Date: 2020-04-28 Impact factor: 1.355