Elsevier

Nutrition

Volume 18, Issue 4, April 2002, Pages 293-297
Nutrition

Fourth Oxford glutamine workshop
Hepatic glutamine metabolism during endotoxemia in neonatal rats

https://doi.org/10.1016/S0899-9007(01)00772-9Get rights and content

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.

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.

Section snippets

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.

Cited by (11)

  • Necrotizing enterocolitis: Prevention, treatment, and outcome

    2013, Journal of Pediatric Surgery
    Citation Excerpt :

    This results in the loss of the protective mucosal barrier and autodigestion and presents an opportunity for bacterial invasion. In addition to these associations, evidence for a vascular component in the etiology of NEC comes from an experimental animal model in which a disease like NEC is observed following an intestinal ischemia reperfusion injury [10]. While the precise role of bacterial agents in the development of NEC is unclear, several factors suggest their involvement.

  • Necrotising enterocolitis

    2018, Rickham's neonatal surgery
  • Endotoxemia and glutamine

    2015, Glutamine in Clinical Nutrition
View all citing articles on Scopus

Guest Editor: Gil Hardy, PhD, FRCS

Paisarn Vejchapipat was supported by Chulalongkorn University, Ministry of University Affairs, Royal Thai Goverment.

View full text