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.

Cerium oxide nanoparticle treatment ameliorates peritonitis-induced diaphragm dysfunction

“…diminished systemic inflammation 15 with the latter occurring most likely due to diminished Kupffer cell activation. 21 In this study, we show that CeO 2 nanoparticle treatment attenuates the diaphragm dysfunction induced by the septic condition. We believe that these are the first data to demonstrate that nanoparticle treatments designed to target the liver Kupffer cells might be useful for preventing the muscle dysfunction and atrophy seen in clinical conditions characterized by severe systemic inflammation.…”

“…21,22 Scanning transmission electron microscopy images were acquired using an aberration-corrected analytical electron microscope For the nanoparticle treatment groups, CeO 2 nanoparticles (0.5 mg/kg) in 200 µL of sterile distilled water were given via the tail vein at the time of peritonitis induction or sham surgery. This dose was chosen based on our preliminary data from pilot studies examining animal mortality and previously published data.…”

“…This dose was chosen based on our preliminary data from pilot studies examining animal mortality and previously published data. 15,21 The sham control and the CI groups received vehicle (200 µL of sterile distilled water). For the biochemical assessments, animals were sacrificed at 3 or 18 hours while functional assessments of diaphragm contractility were performed at 18 hours.…”

Lipopolysaccharide induced MAP kinase activation in RAW 264.7 cells attenuated by cerium oxide nanoparticles

“…This articles contains data related to the research articles entitled "Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles in Biomaterials and Data in Brief article entitled "Cerium oxide nanoparticles inhibit lipopolysaccharide induced MAP kinase/NF-kB mediated severe sepsis" [1,2]. The purpose of this study was to evaluate the contribution of Mitogen Activated Protein Kinase (MAPK) signaling in LPS induced sepsis.…”

“…with the purpose of evaluating whether severe sepsis mortality and associated hepatic dysfunction induced by lipopolysaccharide (LPS) can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the method and processing of raw data related to our study publish in Biomaterials and Data in Brief (Vellaisamy et The data presented in this article and is related to [1,2] Value of the data…”