Cerium oxide nanoparticle treatment ameliorates peritonitis-induced diaphragm dysfunction.
The severe inflammation observed during sepsis is thought to cause diaphragm dysfunction, which is associated with poor patient prognosis. Cerium oxide (CeO2) nanoparticles have been posited to exhibit anti-inflammatory and antioxidative activities suggesting that these particles may be of potential use for the treatment of inflammatory disorders. To investigate this possibility, Sprague Dawley rats were randomly assigned to the following groups: sham control, CeO2 nanoparticle treatment only (0.5 mg/kg iv), sepsis, and sepsis+CeO2 nanoparticles. Sepsis was induced by the introduction of cecal material (600 mg/kg) directly into the peritoneal cavity. Nanoparticle treatment decreased sepsis-associated impairments in diaphragmatic contractile (P(o)) function (sham: 25.6±1.6 N/cm(2) vs CeO2: 23.4±0.8 N/cm(2) vs Sep: 15.9±1.0 N/cm(2) vs Sep+CeO2: 20.0±1.0 N/cm(2), P<0.05). These improvements in diaphragm contractile function were accompanied by a normalization of protein translation signaling (Akt, FOXO-1, and 4EBP1), diminished proteolysis (caspase 8 and ubiquitin levels), and decreased inflammatory signaling (Stat3 and iNOS). Histological analysis suggested that nanoparticle treatment was associated with diminished sarcolemma damage and diminished inflammatory cell infiltration. These data indicate CeO2 nanoparticles may improve diaphragmatic function in the septic laboratory rat.
Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; Department of Pharmacology, Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
Shinichi
S
Asano
Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
Ravikumar
R
Arvapalli
Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; Department of Pharmacology, Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
Nandini D P K
ND
Manne
Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; Department of Pharmacology, Physiology and Toxicology, Joan C Edwards School of Medicine, Marshall University, Huntington, WV, USA.
Mani
M
Maheshwari
Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; Department of Pharmacology, Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
Bing
B
Ma
Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
Kevin M
KM
Rice
Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; Department of Pharmacology, Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
Vellaisamy
V
Selvaraj
Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; Department of Pharmacology, Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA ; Department of Pharmacology, Physiology and Toxicology, Joan C Edwards School of Medicine, Marshall University, Huntington, WV, USA.
Eric R
ER
Blough
D000818:Animals; D015153:Blotting, Western; D002563:Cerium / Q000737:chemistry*; D003964:Diaphragm / Q000187:drug effects*; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry*; D052247:Nitric Oxide Synthase Type II; D010538:Peritonitis / Q000150:complications* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000150:complications* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D012333:RNA, Messenger; D002563:Cerium; C030583:ceric oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
anti-inflammatory; cerium oxide nanoparticles; diaphragm; nitric oxide