Cerium oxide nanoparticle treatment ameliorates peritonitis-induced diaphragm dysfunction

Abstract

The severe inflammation observed during sepsis is thought to cause diaphragm dysfunction, which is associated with poor patient prognosis. Cerium oxide (CeO₂) nanoparticles have been posited to exhibit anti-inflammatory and antioxidative activities suggesting that these particles may be of potential use for the treatment of inflammatory disorders. To investigate this possibility, Sprague Dawley rats were randomly assigned to the following groups: sham control, CeO₂ nanoparticle treatment only (0.5 mg/kg iv), sepsis, and sepsis+CeO₂ nanoparticles. Sepsis was induced by the introduction of cecal material (600 mg/kg) directly into the peritoneal cavity. Nanoparticle treatment decreased sepsis-associated impairments in diaphragmatic contractile (P_o) function (sham: 25.6±1.6 N/cm² vs CeO₂: 23.4±0.8 N/cm² vs Sep: 15.9±1.0 N/cm² vs Sep+CeO₂: 20.0±1.0 N/cm², P<0.05). These improvements in diaphragm contractile function were accompanied by a normalization of protein translation signaling (Akt, FOXO-1, and 4EBP1), diminished proteolysis (caspase 8 and ubiquitin levels), and decreased inflammatory signaling (Stat3 and iNOS). Histological analysis suggested that nanoparticle treatment was associated with diminished sarcolemma damage and diminished inflammatory cell infiltration. These data indicate CeO₂ nanoparticles may improve diaphragmatic function in the septic laboratory rat.

Keywords:

• cerium oxide nanoparticles
• anti-inflammatory
• nitric oxide
• diaphragm

Acknowledgments

This work was supported by DOE (DE-SC0005162) to ERB. The authors would like to acknowledge Niraj Nepal and Geeta Nandyala for sample collection and their technical assistance. The abstract of this article was presented at the Experimental Biology 2015 as a poster presentation with interim findings. The poster’s abstract was published in FASEB journal. Asano et al (2015) Cerium oxide (CeO₂) nanoparticle treatment ameliorates peritonitis induced diaphragm dysfunction. The actual article, however, has never been published.

Disclosure

The authors declare that there are no conflicts of interests regarding the publication of this article.