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Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

Gisele P Oliveira1, Mariana BG Oliveira1, Raquel S Santos1, Letícia D Lima1, Cristina M Dias1, Alexandre M AB' Saber2, Walcy R Teodoro2, Vera L Capelozzi2, Rachel N Gomes3, Patricia T Bozza3, Paolo Pelosi4 and Patricia RM Rocco1*

Author Affiliations

1 Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Rio de Janeiro, 21949-902, Brazil

2 Department of Pathology, Faculty of Medicine, University of São Paulo, Dr. Arnaldo Street, 455, Sao Paulo, 01246-903, Brazil

3 Laboratory of Immunopharmacology, Oswaldo Cruz Institute, FIOCRUZ, Avenida Brasil 4365, Rio de Janeiro, 21045-900, Brazil

4 Department of Ambient, Health and Safety, University of Insubria, c/o Villa Toeplitz Via G.B. Vico, 46 21100 Varese, Italy

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Critical Care 2009, 13:R74  doi:10.1186/cc7888

Published: 19 May 2009

Abstract

Introduction

The protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi.

Methods

Seventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively).

Results

CLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours.

Conclusions

In an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.