Fourth Oxford glutamine workshopHepatic glutamine metabolism during endotoxemia in neonatal rats☆
Introduction
Sepsis is a major cause of illness and death in children.1 Neonates are particularly vulnerable to bacterial infections during the first 4 wk of life as a result of deficiencies in their host defense systems.2 The diverse physiologic manifestations of sepsis are mediated by complex cellular and biochemical events such as cytokine release from inflammatory cells and increased oxidative and metabolic stresses.3 The liver plays a central role during endotoxemia. Interactions among different hepatic cell types, e.g., hepatocytes and hepatic non-parenchymal cells, in endotoxemia are associated with modulations in host defense mechanisms.4 Previous studies from our group showed that, during experimental sepsis, mitochondrial oxygen consumption of hepatocytes is inhibited, whereas extramitochondrial oxygen consumption is increased.5 Similarly, incubation of hepatocytes with mediators of sepsis decreases oxygen consumption.6
Magnetic resonance spectroscopy (MRS) has proven to be a useful technique for the assessment of metabolites containing proton (1H) and phosphorus (31P). The technique of high-resolution 1H and 31P MRS of liver extracts has been used to study the biochemistry of liver metabolism in humans7 and animals.8, 9 The advantage of this technique over other methods of biochemical analysis is that it is a non-destructive, repeatable method. A wide range of metabolites can be delineated synchronously.
We investigated the effects of endotoxemia on liver metabolism, in particular glutamine metabolism, in neonatal rats using an in vivo model.
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Materials and methods
This study was approved under the appropriate animal welfare legislation by the Home Office in the United Kingdom.
Results
None of the rats died during the first 2 h after injections. Thereafter, all lipopolysaccharide-injected animals exhibited signs of endotoxemia as described by Markley et al.5
Discussion
The liver is a prime organ involved in multisystem organ failure during sepsis.4 Neonates are particularly vulnerable to bacterial infections as a result of intrinsic deficiencies in their host defense systems.2 The metabolic responses to sepsis in neonates differ from those in adults, suggesting that data obtained with models of adult sepsis are not applicable to neonatal sepsis.11 In the present study, intraperitoneal injections of lipopolysaccharide to neonatal rats caused significant
Acknowledgements
The authors thank the Wellcome Trust, UK, for provision of the MRS facility, Professor David G. Gadian for his valuable discussion, and Dr. Marcello Zamparelli and Mr. Robin Garett-Cox for their contribution in animal preparation.
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Guest Editor: Gil Hardy, PhD, FRCS
Paisarn Vejchapipat was supported by Chulalongkorn University, Ministry of University Affairs, Royal Thai Goverment.