Glutamine administration ameliorates sepsis-induced kidney injury by downregulating the high-mobility group box protein-1-mediated pathway in mice

Ya Mei Hu, Man Hui Pai, Chiu Li Yeh, Yu-Chen Hou, Sung Ling Yeh

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

Acute kidney injury (AKI) is a severe complication of sepsis. Highmobility group box (HMGB)-1 was implicated as a late mediator of lethal systemic inflammation in sepsis. Since glutamine (GLN) was shown to have anti-inflammatory and antioxidant properties, we hypothesized that GLN administration may downregulate an HMGB-1-mediated pathway and thus ameliorate sepsis-induced AKI. Mice were randomly assigned to a normal group (NC), a septic saline group (SS), or a septic GLN group (SG). Sepsis was induced by cecal ligation and puncture (CLP). The SS group was injected with saline, and the SG group was given 0.75 g GLN/kg body wt once via a tail vein 1 h after CLP. Mice were killed 2, 6, and 24 h after CLP, and blood and kidneys of the animals were harvested for further analysis. The results showed that sepsis resulted in higher mRNA and/or protein expressions of kidney HMGB-1, toll-like receptor (TLR) 4, myeloid differentiation primary-response protein (MyD) 88, and receptor of advanced glycation end products (RAGE) compared with normal mice. Septic mice with GLN administration exhibited decreased HMGB-1, TLR4, RAGE, and phosphorylated NF-κB p65 protein expressions and reduced nitrotyrosine levels in kidney tissues. The histological findings showed that damage to the kidneys was less severe, and survival improved in the SG group. These results indicated that a single dose of GLN administered after the initiation of sepsis plays a prophylactic role in downregulating the expressions of HMGB-1-related mediators and decreasing oxidative stress in the kidneys, which may consequently have ameliorated AKI induced by sepsis.

Original languageEnglish
Pages (from-to)150-158
Number of pages9
JournalAmerican Journal of Physiology - Renal Physiology
Volume302
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Acute kidney injury
  • Glutamine
  • NF-κB p65

ASJC Scopus subject areas

  • Physiology
  • Urology

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