Cerium Oxide Nanoparticles (CeO 2 NP) Treatment Ameliorates Sepsis Induced Diaphragm Dysfunction

CeO 2 nanoparticles have been posited to exhibit anti‐inflammatory and anti‐oxidative activities suggesting that these particles may be of potential use for the treatment of disorders characterized by increased inflammatory/oxidative stress. Severe inflammatory disorders such as that seen during sepsis are associated with diaphragm dysfunction and poor patient prognosis. We hypothesized that CeO 2 nanoparticle treatment would ameliorate diaphragm dysfunction in sepsis by improving the immune response and oxidative stress levels. Sprague Dawley rats were randomly assigned into the following groups: Sham control, CeO 2 nanoparticle treatment only (0.5mg/kg i.v.), sepsis (cecal inoculum method) and sepsis + CeO 2 nanoparticles. Serum cytokine (TNF‐ α, IFN‐γ and IL‐6) levels were elevated at 3 and 18 h after sepsis induction and significantly lowered with CeO 2 nanoparticle treatment (~60 % of Sepsis: P<0.05). Nanoparticle treatment decreased sepsis associated impairments in diaphragmatic contractile (P o ) function (Sham:25.6 ±1.6 N/cm 2 vs. CeO 2 :23.4 ± 0.8 N/cm 2 , vs. Sep:15.9 ± 1.0 N/cm 2 vs. Sep + CeO 2 :20.0 ± 1.0 N/cm 2 , P<0.05). These improvements in contractile function were accompanied by a normalization of protein translation signaling (AKT, S6 and 4EBP), diminished proteolysis (caspase 8 activity and ubiquitin), and decreased inflammatory signaling (Stat3). Histological analysis suggested that nanoparticle treatment was associated with diminished sarcolemma damage and diminished inflammatory cell infiltration. These data indicate CeO 2 nanoparticles may improve diaphragmatic function in the septic laboratory rat.