Date: 19 Feb 2014

Effect of adipose tissue-derived mesenchymal stem cell treatment on oxidative stress and inflammatory response following Escherichia coli lipopolysaccharide

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Abstract

Stem cells are the focus of extensive experimental and clinical research with the aim of replacing lost or damaged tissues. This paper studies the effect of systemic stem cell injections on the redox status of the brain and liver in a model of systemic inflammatory illness. Mice were treated with intraperitoneal (i.p.) injection of adipose tissue-derived mesenchymal stem cell (AT-MSCs) suspension, or saline at time of lipopolysaccharide (LPS; 200 mg/kg, i.p.) administration and euthanized 4 h later. Results show that the administration of LPS increased the oxidative stress in the brain and liver tissues. Malondialdehyde (MDA) increased by 53 and 68.9 %, reduced glutathione (GSH) decreased by 44.4 and 50.6 %, and nitric oxide increased by 47.7 and 87.2 % in the brain and liver, respectively. Total antioxidant capacity (TAC) decreased by 37.8 and 76.2 %, catalase activity decreased by 58.2 and 29.2 %, and paraoxonase 1 (PON1) activity decreased by 53.1 and 22.5 % in the brain and liver, respectively. In addition, nuclear factor kappa B (NF-κB) and the monocyte chemoattractant protein-1 (MCP-1) increased in the brain and liver, respectively, after endotoxin injection. Mice treated with AT-MSCs showed unchanged MDA, increased brain GSH (45.5 %), TAC (171.1 %), catalase activity (58.4 %), and PON1 activity (110.4 %). In the liver, MDA and catalase activity were unchanged, but TAC decreased by −36.7 % and PON1 activity decreased by −22.8 %. NF-κB decreased in the liver, while MCP-1 decreased in the brain and liver by AT-MSCs treatment. AT-MSCs reduced inflammatory cell infiltration and necrotic damage in the liver and markedly decreased the number of degenerated neurons in the cortex and striatum in LPS-treated mice. Stem cell treatment was associated with lower tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and caspase-3 immunoreactivity in the brain (cortex and striatum) and liver tissues compared to that in the LPS control group. Thus, the systemic administration of AT-MSCs suspension in a model of mild systemic illness modulates the cellular oxidative response and exerts anti-inflammatory effect. AT-MSCs prevent tissue injury via decreased nitric oxide generation due to iNOS expression and decreased activation of caspase-3, TNF-α, and MCP-1.