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World J Gastroenterol. Mar 21, 2011; 17(11): 1457-1461 Published online Mar 21, 2011. doi: 10.3748/wjg.v17.i11.1457
Impaired gluconeogenesis in a porcine model of paracetamol induced acute liver failure
Konstantinos J Dabos, Henry R Whalen, Philip N Newsome, John A Parkinson, Neil C Henderson, Ian H Sadler, Peter C Hayes, John N Plevris
Konstantinos J Dabos, Henry R Whalen, Philip N Newsome, Neil C Henderson, Peter C Hayes, John N Plevris, Liver Cell Biology Laboratory, Department of Hepatology, University of Edinburgh, Edinburgh, EH16 4SA, United Kingdom
Konstantinos J Dabos, Gastroenterology Unit, Ioannina General Hospital Hatzikosta, 450-01 Ioannina, Greece
John A Parkinson, Ian H Sadler, Department of Chemistry, University of Edinburgh, Edinburgh, EH16 6AA, United Kingdom
Author contributions: Dabos KJ, Whalen HR, Hayes PC and Plevris JN designed the research; Dabos KJ, Whalen HR, Parkinson JA and Sadler IH performed the NMR experiments; Newsome PN and Henderson NC were responsible for the animal experiments; Dabos KJ and Whalen HR performed the statistical analysis; Dabos KJ and Henderson NC wrote the manuscript.
Correspondence to: Konstantinos J Dabos, MD, PhD, Gastroenterology Department, Hatzikosta General Hospital, Leoforos Makrygianni, 450-01 Ioannina, Greece. kostasophia@yahoo.com
Telephone: +30-26510-80738 Fax: +30-26510-80642
Received: November 21, 2010 Revised: December 22, 2010 Accepted: December 29, 2010 Published online: March 21, 2011
Abstract
AIM: To investigate glucose homeostasis and in particular gluconeogenesis in a large animal model of acute liver failure (ALF).
METHODS: Six pigs with paracetamol induced ALF under general anaesthesia were studied over 25 h. Plasma samples were withdrawn every five hours from a central vein. Three animals were used as controls and were maintained under anaesthesia only. Using 1H NMR spectroscopy we identified most gluconeogenic amino acids along with lactate and pyruvate in the animal plasma samples.
RESULTS: No significant changes were observed in the concentrations of the amino acids studied in the animals maintained under anaesthesia only. If we look at the ALF animals, we observed a statistically significant rise of lactate (P < 0.003) and pyruvate (P < 0.018) at the end of the experiments. We also observed statistically significant rises in the concentrations of alanine (P < 0.002), glycine (P < 0.005), threonine (P < 0.048), tyrosine (P < 0.000), phenylalanine (P < 0.000) and isoleucine (P < 0.01). Valine levels decreased significantly (P < 0.05).
CONCLUSION: Our pig model of ALF is characterized by an altered gluconeogenetic capacity, an impaired tricarboxylic acid (TCA) cycle and a glycolytic state.
