期刊
CRITICAL CARE MEDICINE
卷 43, 期 11, 页码 E477-E489出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0000000000001258
关键词
cerium oxide nanoparticles; dysfunction syndrome; inflammation; multiple organ; peritonitis
资金
- Department of Energy (DOE) [DEPS02-09ER-01]
- DOE [DEPS02-09ER-01]
- Marshall University
Objectives: Peritonitis is a life-threatening disease that is associated with high mortality. The purpose of this study was to determine if cerium oxide nanoparticles can be used to diminish intra-abdominal infection-induced mortality and systemic inflammatory response syndrome in the laboratory rat. Design: Randomized, controlled animal study and cell culture study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rats aged 12 weeks, RAW 246.7 macrophage cell line. Interventions: Intra-abdominal infection or peritonitis was induced by intraperitoneal injection of cecal material (600 mg/kg in 5% sterile dextrose water at a dosage of 5 mL/kg) obtained from healthy donors. Rats in control and peritonitis groups received 200 L of sterile deionized water IV via the tail vein, whereas rats in cerium oxide-only group and peritonitis + cerium oxide group received cerium oxide nanoparticles (0.5 mg/kg) IV at the time of polymicrobial injection. Survival rate was monitored for 14 days, while in other experiments, animals were killed at 3 and 18 hours after induction of peritonitis for biochemical analysis. Measurements and Main Results: Administration of a single dose (0.5 mg/kg) of cerium oxide nanoparticles IV to rats in the peritonitis group significantly improved survival rates and functioned to restore core body temperature toward baseline. Treatment-induced increases in animal survivability were associated with reduced systemic and hepatic oxidative stress, diminished serum cytokines, and chemokine levels. Changes in serum inflammatory markers with treatment were accompanied by decreased monocyte and lymphocyte extravasation into the peritoneal cavity along with decreased infiltration of macrophages into liver. In the heart, treatment diminished extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase-Stat-3 signaling and attenuated endothelial expression of P-selectin and vascular cell adhesion molecule-1. Conclusions: Cerium oxide nanoparticles attenuate the systemic inflammatory response associated with peritonitis, suggesting potential use as a novel therapeutic agent for the treatment of severe intra-abdominal infection.
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