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

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 (CeO(2)NPs) 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 CeO(2)NPs 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 CeO(2)NPs exhibited decreases in LPS-induced cytokine release (TNF-alpha, IL-1 beta, 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 CeO(2)NPs may be useful as a therapeutic agent for sepsis. (C) 2015 Elsevier Ltd. All rights reserved.