Acute kidney injury (AKI) is a severe complication of
sepsis. High-mobility 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.