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Intravenous Glutamine Administration Reduces Lung and Distal Organ Injury in Malnourished Rats With Sepsis

Oliveira, Gisele Pena*; Silva, Johnatas Dutra*; de Araújo, Carla Cristina*; Prota, Luiz Felipe Mancilha; Abreu, Soraia Carvalho*; Madeira, Caroline; Morales, Marcelo Marcos; Takiya, Christina Maeda§; Diaz, Bruno Lourenço; Capelozzi, Vera Luiza; Panizzutti, Rogerio; Pelosi, Paolo**; Rocco, Patricia Rieken Macêdo*

doi: 10.1097/SHK.0000000000000102
Basic Science Aspects

ABSTRACT: Malnutrition is a risk factor for infection, compromising immune response. Glutamine (Gln) protects the lungs and distal organs in well-nourished septic and nonseptic conditions; however, no study to date has analyzed the effects of Gln in the presence of sepsis and malnutrition. In the present work, we tested the hypothesis that early therapy with intravenous Gln prevents lung and distal organ damage in septic malnourished rats. Protein-energy malnutrition was induced in male Wistar rats for 4 weeks. At the end of 4 weeks, malnourished animals were assigned to a sepsis-inducing cecal ligation and puncture group or a sham surgery group. One hour after surgery, animals were given saline (Sal) or L-alanyl-L-glutamine (Gln) intravenously. In addition, a control group (C) was set up with rats fed ad libitum, not submitted to surgery or treatment. Forty-eight hours after surgery, in malnutrition-sham rats, Gln therapy lessened neutrophil lung infiltration and apoptosis in lung and liver. In malnutrition–cecal ligation and puncture rats, Gln therapy yielded (a) reduced static lung elastance, alveolar collapse, inflammation (neutrophil infiltration, interleukin 6), and collagen deposition; (b) repair of types I and II epithelial cells; (c) no significant changes in heat shock protein 70 expression or heat shock factor 1 phosphorylation; (d) a greater number of M1 and M2 macrophages in lung tissue; and (e) less apoptosis in the lung, kidney, small intestine, and liver. In conclusion, early therapy with intravenous Gln reduced inflammation, fibrosis, and apoptosis, minimizing lung and distal organ injury, in septic malnourished rats. These beneficial effects may be associated with macrophage activation in the lung.

Laboratories of *Pulmonary Investigation and Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Laboratory of Frontiers in Neuroscience, Institute of Biomedical Sciences, and Laboratories of §Cellular Pathology and Inflammation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro; Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil; and **IRCCS AOU San Martino-IST, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy

Received 15 Jul 2013; first review completed 30 Jul 2013; accepted in final form 26 Nov 2013

Address reprint requests to Patricia Rieken Macêdo Rocco, MD, PhD, Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Avenida Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, Brazil. E-mail:

Source of funding: Centers of Excellence Program (PRONEX-FAPERJ), Brazilian Council for Scientific and Technological Development (CNPq), Rio de Janeiro State Research Foundation (FAPERJ), São Paulo State Research Foundation (FAPESP), National Institute of Science and Technology for Drugs and Medicine (INCT-INOFAR), Coordination for the Improvement of Higher Level Personnel (CAPES), and the European Community’s Seventh Framework Programme (TARKINAID, FP7-2007–2013).

The authors have no conflicts of interest to declare.

© 2014 by the Shock Society