Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles

Details

• Personal Author:
  Arvapalli R ; Asano S ; Blough ER ; Fankhanel E ; Ma JJ ; Maheshwari M ; Manne NDPK ; Nepal N ; Rice KM ; Rogers S ; Selvaraj V ; Shokuhfar T
• Description:
  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-alpha, IL-1beta, 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. [Description provided by NIOSH]
• Subjects:
  Blood Body Temperature Communicable Diseases Digestive System Digestive System Diseases Endotoxins Environmental Monitoring Immune System Laboratories Lipids Liver Occupational Health Respiratory System Safety

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• Keywords:
  Author Keywords: Cerium Oxide Nanoparticles Bacteria Blood-cells Blood-pressure Body-temperature Cell-damage Cell-function Cellular-reactions Cerium-compounds Cytokines Exposure-assessment Exposure-levels Immune-reaction Immune-system Immune-system-disorders Infection-control Laboratory-animals Laboratory-testing Lipopolysaccharide Liver-cells Liver-damage Liver-function Macrophage Nanotechnology Oxidative-processes Polysaccharides Respiration Sepsis Survival-rate Therapeutic-agents

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• ISSN:
  0142-9612
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Michigan ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  160-171
• Volume:
  59
• NIOSHTIC Number:
  nn:20046246
• Citation:
  Biomaterials 2015 Aug; 59:160-171
• Contact Point Address:
  Eric R. Blough, Center for Diagnostic Nanosystems, Room 241R, Robert C. Byrd Biotechnology Science Center Building, Department of Pharmaceutical Science and Research, 1700 3rd Ave., Marshall University, Huntington, WV 25755-1090
• Email:
  blough@marshall.edu
• CAS Registry Number:
  Ceria (CAS RN 1306-38-3) ; Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2015
• Peer Reviewed:
  True
• Source Full Name:
  Biomaterials
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b59a6a92c532f2b498f515a068c8dbf5790d8fd369a67cfed7997bd8e9457170cab259be0c350a20b9045862e77a26faf70c698bb773b38f0d4d391be8b1ccac
• Download URL:
  https://stacks.cdc.gov/view/cdc/201355/cdc_201355_DS1.pdf
• File Type:
  [PDF - 4.29 MB ]