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

Oliveira GP, Oliveira MB, Santos RS, Lima LD, Dias CM, Ab' Saber AM, Teodoro WR, Capelozzi VL, Gomes RN, Bozza PT, Pelosi P, Rocco PR - Crit Care (2009)

Bottom Line: 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.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.These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21949-902, Brazil. giselepoliv@gmail.com

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.

Show MeSH

Related in: MedlinePlus

Representative photomicrographs of lung parenchyma in C-SAL, C-Gln, CLP-SAL and CLP-Gln.  In CLP group, animals were submitted to cecal ligation and puncture technique. A sham-operated group was used as control (C) for animals undergoing CLP. One hour after surgery, C and CLP groups were treated with saline (SAL) or glutamine (Gln). Note the areas of alveolar collapse (arrows). Photomicrographs were taken at an original magnification of × 200 from slides stained by haematoxylin & eosin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2717436&req=5

Figure 2: Representative photomicrographs of lung parenchyma in C-SAL, C-Gln, CLP-SAL and CLP-Gln. In CLP group, animals were submitted to cecal ligation and puncture technique. A sham-operated group was used as control (C) for animals undergoing CLP. One hour after surgery, C and CLP groups were treated with saline (SAL) or glutamine (Gln). Note the areas of alveolar collapse (arrows). Photomicrographs were taken at an original magnification of × 200 from slides stained by haematoxylin & eosin.

Mentions: In CLP-SAL, lung histology presented neutrophil infiltration, alveolar collapse, interstitial oedema (Table 1 and Figure 2), distortion of lung parenchymal structure, degeneration of lamellar bodies, damage in microvilli, and apoptosis in type II pneumocytes (Figure 3). Note in CLP-Gln regeneration and restoration of the acinar architecture (Figure 3 and Table 2) with tridimensional reconstruction at confocal microscopy (Figure 4). Electronic microscopy of the diaphragm showed oedema between muscle fibres, mitochondrial injury, and apoptosis in muscle cells (Figure 5 and Table 2), while Gln attenuated these morphological changes (Figure 5).


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

Oliveira GP, Oliveira MB, Santos RS, Lima LD, Dias CM, Ab' Saber AM, Teodoro WR, Capelozzi VL, Gomes RN, Bozza PT, Pelosi P, Rocco PR - Crit Care (2009)

Representative photomicrographs of lung parenchyma in C-SAL, C-Gln, CLP-SAL and CLP-Gln.  In CLP group, animals were submitted to cecal ligation and puncture technique. A sham-operated group was used as control (C) for animals undergoing CLP. One hour after surgery, C and CLP groups were treated with saline (SAL) or glutamine (Gln). Note the areas of alveolar collapse (arrows). Photomicrographs were taken at an original magnification of × 200 from slides stained by haematoxylin & eosin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2717436&req=5

Figure 2: Representative photomicrographs of lung parenchyma in C-SAL, C-Gln, CLP-SAL and CLP-Gln. In CLP group, animals were submitted to cecal ligation and puncture technique. A sham-operated group was used as control (C) for animals undergoing CLP. One hour after surgery, C and CLP groups were treated with saline (SAL) or glutamine (Gln). Note the areas of alveolar collapse (arrows). Photomicrographs were taken at an original magnification of × 200 from slides stained by haematoxylin & eosin.
Mentions: In CLP-SAL, lung histology presented neutrophil infiltration, alveolar collapse, interstitial oedema (Table 1 and Figure 2), distortion of lung parenchymal structure, degeneration of lamellar bodies, damage in microvilli, and apoptosis in type II pneumocytes (Figure 3). Note in CLP-Gln regeneration and restoration of the acinar architecture (Figure 3 and Table 2) with tridimensional reconstruction at confocal microscopy (Figure 4). Electronic microscopy of the diaphragm showed oedema between muscle fibres, mitochondrial injury, and apoptosis in muscle cells (Figure 5 and Table 2), while Gln attenuated these morphological changes (Figure 5).

Bottom Line: 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.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.These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21949-902, Brazil. giselepoliv@gmail.com

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.

Show MeSH
Related in: MedlinePlus