Prevention of hemorrhagic shock-induced intestinal tissue injury by glutamine via heme oxygenase 1 induction

Kana Umeda, Toru Takahashi, Kazuyoshi Inoue, Hiroko Shimizu, Shigeru Maeda, Hiroshi Morimatsu, Emiko Omori, Reiko Akagi, Hiroshi Katayama, Kiyoshi Morita

Research output: Contribution to journalArticle

34 Citations (Scopus)

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-α, 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.

Original languageEnglish
Pages (from-to)40-49
Number of pages10
JournalShock
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 2009

Fingerprint

Heme Oxygenase-1
Hemorrhagic Shock
Glutamine
Ileum
Wounds and Injuries
Oxidative Stress
Gene Expression
Vascular Cell Adhesion Molecule-1
DNA Fragmentation
Intercellular Adhesion Molecule-1
Caspase 3
Interleukin-10
Peroxidase
Intestines
Ligation
Neutrophils
Cell Death
Anti-Inflammatory Agents
Epithelial Cells
Inflammation

Keywords

  • Apoptosis
  • Ileum
  • Inflammation
  • Oxidative stress
  • Tin mesoporphyrin

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Prevention of hemorrhagic shock-induced intestinal tissue injury by glutamine via heme oxygenase 1 induction. / Umeda, Kana; Takahashi, Toru; Inoue, Kazuyoshi; Shimizu, Hiroko; Maeda, Shigeru; Morimatsu, Hiroshi; Omori, Emiko; Akagi, Reiko; Katayama, Hiroshi; Morita, Kiyoshi.

In: Shock, Vol. 31, No. 1, 01.2009, p. 40-49.

Research output: Contribution to journalArticle

Umeda, K, Takahashi, T, Inoue, K, Shimizu, H, Maeda, S, Morimatsu, H, Omori, E, Akagi, R, Katayama, H & Morita, K 2009, 'Prevention of hemorrhagic shock-induced intestinal tissue injury by glutamine via heme oxygenase 1 induction', Shock, vol. 31, no. 1, pp. 40-49. https://doi.org/10.1097/SHK.0b013e318177823a
Umeda, Kana ; Takahashi, Toru ; Inoue, Kazuyoshi ; Shimizu, Hiroko ; Maeda, Shigeru ; Morimatsu, Hiroshi ; Omori, Emiko ; Akagi, Reiko ; Katayama, Hiroshi ; Morita, Kiyoshi. / Prevention of hemorrhagic shock-induced intestinal tissue injury by glutamine via heme oxygenase 1 induction. In: Shock. 2009 ; Vol. 31, No. 1. pp. 40-49.
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AB - 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-α, 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.

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