title: Acute inhalation toxicity of cerium oxide nanoparticles in rats.
abstract: The aim of the present study was to assess the acute toxic potential of cerium oxide nanoparticles (CeO(2) NPs) in rats when exposed through the head and nose inhalation route. The rats were exposed to CeO(2) NPs and the resultant effects if any, to cause cytotoxicity, oxidative stress and inflammation in the lungs were evaluated on a 24h, 48h and 14 day post exposure period. Our results showed a significant decrease in the cell viability, with the increase of lactate dehydogenase, total protein and alkaline phosphatase levels in the bronchoalveolar lavage fluid (BALF) of the exposed rats. Total leukocyte count and the percentage of neutrophils in BALF were elevated within 24h of post exposure. The concentrations of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) were significantly increased in the BALF and in the blood throughout the observation period. The level of malondialdehyde was elevated with the decreased levels of intracellular reduced glutathione (GSH) in the lung after exposure. The alveolar macrophages (AMs) and neutrophils overloaded with phagocytosed CeO(2) NPs were observed along with non-phagocytosed free CeO(2) NPs that were deposited over the epithelial surfaces of the bronchi, bronchiole and alveolar regions of lungs within 24h of post exposure and were consistent throughout the observation period. A well distributed, multifocal pulmonary microgranulomas due to impairment of clearance mechanism leading to biopersistence of CeO(2) NPs for an extended period of time were observed at the end of the 14 day post exposure period. These results suggest that acute exposure of CeO(2) NPs through inhalation route may induce cytotoxicity via oxidative stress and may lead to a chronic inflammatory response.
authors.affiliation: Department of Toxicology, International Institute of Biotechnology and Toxicology (IIBAT), Padappai 601301, Tamil Nadu, India. vasualapati@gmail.com
authors.forename: A
authors.initials: A
authors.lastname: Srinivas
authors.forename: P Jaganmohan
authors.initials: PJ
authors.lastname: Rao
authors.forename: G
authors.initials: G
authors.lastname: Selvam
authors.forename: P Balakrishna
authors.initials: PB
authors.lastname: Murthy
authors.forename: P Neelakanta
authors.initials: PN
authors.lastname: Reddy
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002563:Cerium / Q000633:toxicity*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D053758:Nanoparticles / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D023382:Toxicity Tests, Acute
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D002563:Cerium; C030583:ceric oxide