Cerium Oxide Nanoparticles Confer Protection against Severe Sepsis Induced Hepatic Inflammation and Injury in Sprague Dawley Rats

Abstract

Severe sepsis is a medical emergency that is characterized by high mortality. The acute nature of this disease is characterized by high levels of inflammatory mediators that cause multiple organ damage and death. Despite recent advances in medical care, most of the deaths due to sepsis are related to the reactive oxygen species (ROS) induced release of inflammatory mediators by host immune system in response to invading pathogens. Current treatment regime is largely supportive in nature and does not focus on the underlying cause. Studies have shown that cerium oxide (CeO2) nanoparticles have the intrinsic ability to scavenge ROS along with anti‐bacterial activity. Based on these unique properties, we hypothesized whether CeO2 nanoparticles could diminish sepsis‐induced mortality and associated hepatic damage. Male Sprague Dawley rats were subjected to a severe septic insult with 600mg/kg of cecal inoculum and treated with 0.5mg/kg of CeO2 nanoparticles intravenously. Our preliminary data suggests that the CeO2 nanoparticles improved animal survivability and attenuated hepatic superoxide levels. These changes were also accompanied by decrease in hepatic levels of iNOS and nitrotyrosine along with reduced macrophage infiltration. CeO2 nanoparticle treatment also attenuated sepsis induced increase in GST‐α and GST‐Mu by 15‐and 19‐fold respectively. Taken together, these data suggest that CeO2 nanoparticles may be used for the treatment of severe sepsis.