Hepatic glutamine metabolism during endotoxemia in neonatal rats

Abstract Objectives: The liver plays a central role during endotoxemia. We investigated the biochemical changes that occur in neonatal liver during early stages of endotoxemia. Methods: Twenty neonatal rats (10 to 15 d; n = 10/group) were studied. Endotoxemic rats received intraperitoneal injections of 300 μg/kg of 12.5 mg/L of lipopolysaccharide and control rats received isovolemic normal saline. Two hours after injection, all lipopolysaccharide-injected animals exhibited signs of endotoxemia. Livers were removed and extracted into 12% perchloric acid. 1H and 31P magnetic resonance spectroscopy measured hepatic levels of glutamine, glutamate, alanine, lactate, glucose, β-hydroxybutyrate, adenosine triphosphate, and adenosine diphosphate. Unpaired t test compared groups. Results: No mortality occurred during the first 2 h after injection. Endotoxemia significantly decreased hepatic levels of glutamine (P < 0.001), glucose (P = 0.047), and β-hydroxybutyrate (P < 0.001). There was no difference in hepatic levels of glutamate (P = 0.050), alanine (P = 0.165), lactate (P = 0.478), adenosine triphosphate (P = 0.165), and adenosine diphosphate (P = 0.136) between groups. Conclusions: Early endotoxemia caused significant changes in the hepatic metabolism of glutamine, glucose, and β-hydroxybutyrate. These findings increase our understanding of the pathophysiology of neonatal endotoxemia.