Europium‐Doped Cerium Oxide Nanoparticles Limit Reactive Oxygen Species Formation and Ameliorate Intestinal Ischemia–Reperfusion Injury

• Published in: Advanced healthcare materials 2017-07, Vol.6 (14), p.n/a
• Main Authors: Gubernatorova, Ekaterina O., Liu, Xiaobo, Othman, Ali, Muraoka, Wayne T., Koroleva, Ekaterina P., Andreescu, Silvana, Tumanov, Alexei V.
• Format: Article
• Language: English
• Subjects: Accumulation; Animals; Cerium; Cerium - chemistry; Cerium - pharmacology; cerium oxide nanoparticles; Cerium oxides; Cytokines; electrochemical biosensors; Europium; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; In vitro methods and tests; Inflammation; Injury prevention; Interleukin 1; Interleukin-1beta - metabolism; Intestinal Diseases - drug therapy; Intestinal Diseases - metabolism; Intestinal Diseases - pathology; intestinal injury; Intestine; Intestines - metabolism; Intestines - pathology; Ischemia; Mice; Mucosa; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Oxidation; Pathology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reperfusion; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Rodents; Scavengers; Scavenging; Superoxide
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201700176

Accumulating evidence suggests that ischemia–reperfusion‐induced injury is associated with the formation of reactive oxygen species (ROS). This study demonstrates the therapeutic effectiveness of novel europium‐doped cerium oxide nanoparticles (Eu‐doped Ceria NPs) as ROS scavengers in a mouse model of intestinal ischemia–reperfusion‐induced injury. An increased production of superoxide radicals is detected in the intestine throughout the ischemia stage and again after initiating reperfusion. These changes in superoxide radical formation are associated with the induction of inflammatory cytokines in the intestine. This study further shows that Eu‐Ceria NPs exhibit superoxide scavenging activity in vitro. Importantly, administration of Eu‐Ceria NPs into the intestinal lumen during the onset of ischemia effectively blocks superoxide accumulation, reduces the expression of IL‐1b, and ameliorates the intestinal pathology. These results suggest that early increased production of ROS during the ischemia–reperfusion promotes intestinal pathology and that mucosal delivery of Eu‐Ceria NPs may be a potential therapeutic approach to block ROS accumulation and ameliorate the severity of intestinal disease. Europium‐doped cerium oxide nanoparticles (Eu‐Cerium NPs) effectively block formation of reactive oxygen species (ROS). ROS are detected in live intestine in real‐time using superoxide electrochemical biosensor. Authors demonstrate that early increase of ROS during ischemia–reperfusion promotes intestinal injury and that mucosal delivery of Eu‐Ceria NPs can be a therapeutic approach to block ROS and reduce the severity of intestinal disease.