title: Intravenous glutamine administration reduces lung and distal organ injury in malnourished rats with sepsis.
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.
authors.affiliation: 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.
authors.forename: Gisele Pena
authors.initials: GP
authors.lastname: de Oliveira
authors.forename: Johnatas Dutra
authors.initials: JD
authors.lastname: Silva
authors.forename: Carla Cristina
authors.initials: CC
authors.lastname: de Araújo
authors.forename: Luiz Felipe Mancilha
authors.initials: LF
authors.lastname: Prota
authors.forename: Soraia Carvalho
authors.initials: SC
authors.lastname: Abreu
authors.forename: Caroline
authors.initials: C
authors.lastname: Madeira
authors.forename: Marcelo Marcos
authors.initials: MM
authors.lastname: Morales
authors.forename: Christina Maeda
authors.initials: CM
authors.lastname: Takiya
authors.forename: Bruno Lourenço
authors.initials: BL
authors.lastname: Diaz
authors.forename: Vera Luiza
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Rogerio
authors.initials: R
authors.lastname: Panizzutti
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.forename: Patricia Rieken Macêdo
authors.initials: PR
authors.lastname: Rocco
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D005973:Glutamine / Q000008:administration & dosage*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood; D055370:Lung Injury / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D044342:Malnutrition / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009102:Multiple Organ Failure / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018836:Inflammation Mediators; D005973:Glutamine