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• W2005706952 abstract "In Brief Objective Oxidative stress and subsequent lipid peroxidation appear to be central to the lethal effect of lipopolysaccharide. We hypothesized that induction of an antioxidant protein, thioredoxin, would play an important role in the development of endotoxin tolerance and reduce mortality rates in lipopolysaccharide-treated mice. Design Prospective, randomized, controlled study. Setting University research laboratory. Subjects Adult, male, ddy mice. Interventions In survival-curve experiments, mice were pretreated intravenously with a low dose of Escherichia coli lipopolysaccharide (20 μg/mouse, pretreatment group) or saline (control group). A large dose of lipopolysaccharide (200 μg/mouse) subsequently was injected into the tail vein 16 hrs after pretreatment. In experiments to measure the expression of thioredoxin after lipopolysaccharide challenge, mice were injected intravenously with different concentrations of lipopolysaccharide (between 20 and 200 μg/mouse, designated the lipopolysaccharide group) or with saline (control group). Measurements and Main Results The survival rate during the 72-hr observation period was significantly higher in the pretreatment group (82%) than in the control group (30%;p = .025 by Mantel-Cox log rank analysis). After lipopolysaccharide challenge, thioredoxin concentrations in the lung, heart, and liver of mice in the pretreated group were about 1.5- to 2-fold higher than those in the control group. Enhancement in these organs became apparent about 6 hrs after lipopolysaccharide challenge and lasted until at least 24 hrs. The levels of accumulation of 4-hydroxy-2-nonenal modified proteins after a large dose of lipopolysaccharide challenge were lower in the pretreatment group than in the control group. Conclusions These results demonstrate that mice with an increased concentration of thioredoxin, induced by pretreatment with a low dose of lipopolysaccharide, had increased survival when given a subsequent high-dose challenge of lipopolysaccharide. Thus, thioredoxin is associated with the development of endotoxin tolerance in mice. In this model of sepsis, induced thioredoxin may play an important role in the develop-ment of endotoxin tolerance via inhibition of lipid peroxidation." @default.
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• W2005706952 date "2002-01-01" @default.
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• W2005706952 title "Thioredoxin is associated with endotoxin tolerance in mice" @default.
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• W2005706952 doi "https://doi.org/10.1097/00003246-200201000-00027" @default.
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