title: Prevention of hemorrhagic shock-induced intestinal tissue injury by glutamine via heme oxygenase-1 induction.
abstract: Hemorrhagic shock (HS) is an oxidative stress that causes intestinal tissue injury. Heme oxygenase 1 (HO-1) is induced by oxidative stress and is thought to play an important role in the protection of tissues from oxidative injury. We previously reported the ileum to be the most susceptible to HS-induced tissue injury site in the intestine because HO-1 induction is the lowest at this site. We also previously demonstrated that glutamine (GLN) significantly induced HO-1 in the lower intestinal tract. In the present study, we investigated whether GLN pretreatment improves HS-induced intestinal tissue injury in the ileum by HO-1 induction. Treatment of rats with GLN (0.75 g/kg, i.v.) markedly induced functional HO-1 protein in mucosal epithelial cells in the ileum. Glutamine treatment before HS (MAP of 30 mmHg for 60 min) significantly ameliorated HS-induced mucosal inflammation and apoptotic cell death in the ileum, as judged by significant decreases in gene expression of TNF-alpha, iNOS, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1, myeloperoxidase activity, the number of infiltrated neutrophils, DNA fragmentation by in situ oligo ligation assay, and activated caspase-3 expression, and by increases in gene expression of IL-10 and Bcl-2. In contrast, treatment with tin mesoporphyrin, a specific inhibitor of HO activity, abolished the beneficial effect of GLN pretreatment. These findings indicate that GLN pretreatment significantly ameliorated tissue injury in the ileum after HS by inducing HO-1. Glutamine treatment may thus protect mucosal cells from HS-induced oxidative damage via the anti-inflammatory and antiapoptotic properties of HO-1.
authors.affiliation: Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Umeda
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Inoue
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shimizu
authors.forename: Shigeru
authors.initials: S
authors.lastname: Maeda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morimatsu
authors.forename: Emiko
authors.initials: E
authors.lastname: Omori
authors.forename: Reiko
authors.initials: R
authors.lastname: Akagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katayama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Morita
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007077:Ileal Diseases / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D007082:Ileum / Q000201:enzymology / Q000473:pathology; D007249:Inflammation / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000293:injuries* / Q000473:pathology; D008297:Male; D008652:Mesoporphyrins / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D004791:Enzyme Inhibitors; D008652:Mesoporphyrins; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D005973:Glutamine; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; C031468:mesoporphyrin IX; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051547:Heme Oxygenase-1; C505410:Casp3 protein, rat; D053148:Caspase 3