Abstract | OBJECTIVES: 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 μL 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:
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Authors | Nandini D P K Manne, Ravikumar Arvapalli, Niraj Nepal, Srinivasarao Thulluri, Vellaisamy Selvaraj, Tolou Shokuhfar, Kun He, Kevin M Rice, Shinichi Asano, Mani Maheshwari, Eric R Blough |
Journal | Critical care medicine
(Crit Care Med)
Vol. 43
Issue 11
Pg. e477-89
(Nov 2015)
ISSN: 1530-0293 [Electronic] United States |
PMID | 26327202
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Reactive Oxygen Species
- Cerium
- ceric oxide
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Topics |
- Analysis of Variance
- Animals
- Biopsy, Needle
- Cerium
(therapeutic use)
- Disease Models, Animal
- Immunoblotting
- Immunohistochemistry
- Injections, Intraperitoneal
- Male
- Nanoparticles
(therapeutic use)
- Oxidative Stress
(physiology)
- Peritonitis
(drug therapy, microbiology, mortality)
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Reactive Oxygen Species
(metabolism)
- Reference Values
- Survival Rate
- Treatment Outcome
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