title: Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles.
abstract: Sepsis is a life threatening disease that is associated with high mortality. Existing treatments have failed to improve survivability in septic patients. The purpose of this present study is to evaluate whether cerium oxide nanoparticles (CeO2NPs) can prevent lipopolysaccharide (LPS) induced severe sepsis mortality by preventing hepatic dysfunction in male Sprague Dawley rats. Administration of a single dose (0.5 mg/kg) of CeO2NPs intravenously to septic rats significantly improved survival rates and functioned to restore body temperature, respiratory rate and blood pressure towards baseline. Treatment-induced increases in animal survivability were associated with decreased hepatic damage along with reductions in serum cytokines/chemokines, and diminished inflammatory related signaling. Kupffer cells and macrophage cells exposed to CeO2NPs exhibited decreases in LPS-induced cytokine release (TNF-α, IL-1β, IL-6, HMGB1) which were associated with diminished cellular ROS, reduced levels of nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and decreased nuclear factor-kappa light chain enhancer of activated B cells (NF-kB) transcriptional activity. The findings of this study indicate that CeO2NPs may be useful as a therapeutic agent for sepsis.
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Vellaisamy
authors.initials: V
authors.lastname: Selvaraj
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Niraj
authors.initials: N
authors.lastname: Nepal
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Rogers
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Nandini D P K
authors.initials: ND
authors.lastname: Manne
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Arvapalli
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rice
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Asano
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Fankhanel
authors.affiliation: Health Effects Laboratory Division, NIOSH, Morgantown, WV, USA.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Ma
authors.affiliation: Department of Mechanical Engineering and Engineering Mechanics, Michigan Technological University, Houghton, MI, USA.
authors.forename: Tolou
authors.initials: T
authors.lastname: Shokuhfar
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Mani
authors.initials: M
authors.lastname: Maheshwari
authors.affiliation: 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; Department of Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA; Department of Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA. Electronic address: blough@marshall.edu.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Blough
mesh_terms: D000818:Animals; D002563:Cerium / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity*; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D051381:Rats; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy*; D015398:Signal Transduction
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D002563:Cerium; C030583:ceric oxide; D020928:Mitogen-Activated Protein Kinases
keywords: Cerium oxide nanoparticles; Cytokines; Lipopolysaccharide; Macrophage; Sepsis