title: Cerium oxide nanoparticles protect rodent lungs from hypobaric hypoxia-induced oxidative stress and inflammation.
abstract: BACKGROUND
  Cerium oxide nanoparticles (nanoceria) are effective at quenching reactive oxygen species (ROS) in cell culture and animal models. Although nanoceria reportedly deposit in lungs, their efficacy in conferring lung protection during oxidative stress remains unexplored. Thus, the study evaluated the protective efficacy of nanoceria in rat lung tissue during hypobaric hypoxia.
  
  
  METHODS
  A total of 48 animals were randomly divided into four equal groups (control [C], nanoceria treated [T], hypoxia [H], and nanoceria treated plus hypoxia [T+H]). Animals were injected intraperitoneally with either a dose of 0.5 μg/kg body weight/week of nanoceria (T and T+H groups) or vehicle (C and H groups) for 5 weeks. After the final dose, H and T+H animals were challenged with hypobaric hypoxia, while C and T animals were maintained at normoxia. Lungs were isolated and homogenate was obtained for analysis of ROS, lipid peroxidation, glutathione, protein carbonylation, and 4-hydroxynonenal-adduct formation. Plasma was used for estimating major inflammatory cytokines using enzyme-linked immunosorbent assay. Intact lung tissues were fixed and both transmission electron microscopy and histopathological examinations were carried out separately for detecting internalization of nanoparticles as well as altered lung morphology.
  
  
  RESULTS
  Spherical nanoceria of 7-10 nm diameter were synthesized using a microemulsion method, and the lung protective efficacy of the nanoceria evaluated during hypobaric hypoxia. With repeated intraperitoneal injections of low micromole concentration, we successfully localized the nanoceria in rodent lung without any inflammatory response. The lung-deposited nanoceria limited ROS formation, lipid peroxidation, and glutathione oxidation, and prevented oxidative protein modifications like nitration and carbonyl formation during hypobaric hypoxia. We also observed reduced lung inflammation in the nanoceria-injected lungs, supporting the anti-inflammatory properties of nanoceria.
  
  
  CONCLUSIONS
  Cumulatively, these results suggest nanoceria deposit in lungs, confer protection by quenching noxious free radicals during hypobaric hypoxia, and do not evoke any inflammatory response.
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Delhi, India.
authors.forename: Aditya
authors.initials: A
authors.lastname: Arya
authors.forename: Niroj Kumar
authors.initials: NK
authors.lastname: Sethy
authors.forename: Sushil Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Mainak
authors.initials: M
authors.lastname: Das
authors.forename: Kalpana
authors.initials: K
authors.lastname: Bhargava
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002563:Cerium / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011014:Pneumonia / Q000378:metabolism* / Q000473:pathology; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D020011:Protective Agents; D002563:Cerium; C030583:ceric oxide
keywords: high altitude; nanoceria; nanomedicine