Acute inhalation toxicity of cerium oxide nanoparticles in rats
Highlights
► The ability of the CeO2 NPs exposed by head and nose inhalation route to cause the lung toxicity was evaluated. ► Results showed induction of cytotoxicity, oxidative stress and inflammation in lung. ► Existing of CeO2 NPs in free and engulfed forms was observed in lung which resulted in the formation of microgranuloma. ► Acute inhalation exposure of CeO2 NPs induced cytotoxicity via oxidative stress which led to chronic inflammation.
Introduction
Lanthanide cerium oxide (CeO2) nanoparticles (NPs) have extensive applications and widespread use as catalysts, solar cells, solid fuel cells, ultraviolet absorbents, as phosphor/luminescence, automotive catalytic converters, gas sensors, oxygen pumps and metallurgical and glass/ceramic applications (Murray et al., 1999, Corma et al., 2004, Izu et al., 2004, Sato et al., 2004, Zheng et al., 2005). Extensive usage of CeO2 NPs in manufacturing industries has raised the possibility of occupational and environmental health concerns of humans exposed to them. Occupational exposure to cerium oxide has been reported to cause pneumoconiosis (Pairon et al., 1994, McDonald et al., 1995). OECD established a Working Party on Manufactured Nanomaterials (WPMN) to assess the human health and environmental safety implications of manufactured nanomaterials and included CeO2 NPs as one of the 13 priority listed representative manufactured nanomaterials [ENV/JM/MONO(2008)13/REV]. A number of recent publications have shown that exposure to CeO2 NPs can cause adverse effect to human health through generation of reactive oxygen species (ROS), leading to oxidative stress, inflammation and which leads to stress-induced programmed cell death (apoptosis) (Thill et al., 2006, Park et al., 2008, Eom and Choi, 2009). In contrast some studies reported CeO2 NPs exhibiting antioxidant properties that promote cell survival under conditions of oxidative stress and have a potential for their use in cardio, neuroprotective and retinoprotective therapeutic purposes (Chung, 2003, Chen et al., 2006, Schubert et al., 2006, Das et al., 2007, Niu et al., 2007, Patil et al., 2007, Karakoti et al., 2008). In his recent publication Niu et al. (2011) reported the ability of CeO2 NPs to protect against cigarette smoke extract (CSE)-induced oxidative stress, inflammation and cell damage inflammation in cultured rat H9c2 cardiomyocytes via inhibition of ROS generation, NF-кB activation, inflammatory gene expression and antioxidant depletion.
However, most of the works addressing CeO2 NPs toxicity have only used in vitro models or in vivo intratracheal instillation methods. This lead us to conduct the present study were we made an attempt to assess the acute toxicological effects of CeO2 NPs in rats exposed by head and nose inhalation route. We believe inhalation as the most probable route of exposure for NPs in occupational hazards and simulate human exposure to nanoparticles to observe their health effects experimentally. Further, Madl and Pinkerton (2009) opined that, inhalation exposure provides a natural way for delivery of toxicants; deposition and clearance patterns comparable to that in a real world setting; to evaluate effects at all levels of the respiratory tract and result in even distribution of the delivered toxicant. The present study was undertaken to deliver data on biochemical, hematological, BALF analysis for cytotoxicity and pro inflammatory cytokine responses, oxidative levels in lung and histopathological changes of target organs after a single 4 h continuous head and nose inhalation exposure of CeO2 NPs.
Section snippets
CeO2 nanoparticles
The CeO2 NPs with a primary particle diameter of 15–30 nm and 30–50 m2/g specific surface area (SSA) tested in this study was purchased from Nanostructured and Amorphous Materials, Inc., USA. The average size of the particle was reconfirmed by scanning electron microscopy (SEM) (Fig. 1) and the crystal form by X-ray diffraction (XRD). The characterizations of the CeO2 nanoparticles were shown in Table 1.
Animals
Seventy-two healthy Wistar rats of either sex, aged 8 weeks and weighing 180–200 g were
CeO2 NPs characterization
Prior to the conduct of acute inhalation exposure, characterization of the CeO2 NPs was performed using SEM and XRD methods, which provided information on the size and crystalline structure respectively (Fig. 1 and Table 1). The size of nanoparticles confirmed by SEM was 55 nm, which was higher than the size reported by its commercial supplier. This difference in sizes can be attributed to fact that different size determination methods, i.e., TEM and SEM employed by the manufacturer and us
Discussion
This study was designed to assess the acute inhalation toxicity of CeO2 NPs with rat as animal model. In this study rats were subjected to 4 h continuous exposure of CeO2 NPs at 641 mg/m3 dose concentration. Following exposures, blood was collected from orbital sinus of the rats in the study for biochemical and hematological end points at 24 h, 48 h and 14 days post exposure period to assess the acute toxicity. Simultaneously, the lungs of rats in the study were lavaged and pro inflammation and
Conflict of interest
None.
Acknowledgements
The authors are grateful to the IIBAT management for providing support for this work. We thank M. Goparaju for his cooperation in statistical analysis and B. Siva Prakash and M. Sai Kumar for their contribution to the laboratory work. We thank Dr. P. Srivatsa for critically reviewing the manuscript.
References (57)
- et al.
The primary role of iron-mediated lipid peroxidation in the differential cytotoxicity caused by two varieties of talc nanoparticles on A549 cells and lipid peroxidation inhibitory effect exerted by ascorbic acid
Toxicol. In Vitro
(2010) - et al.
Pro-inflammatory responses of human bronchial epithelial cells to acute nitrogen dioxide exposure
Toxicology
(2004) - et al.
Differential particulate air pollution induced oxidant stress in human granulocytes, monocytes and alveolar macrophages
Toxicol. In Vitro
(2002) - et al.
Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons
Biomaterials
(2007) Tissue sulfhydryl groups
Arch. Biochem. Biophys.
(1959)- et al.
Oxidative stress of CeO2 nanoparticles via p38-Nrf-2 signaling pathway in human bronchial epithelial cell, Beas-2B
Toxicol. Lett.
(2009) - et al.
Respiratory system
- et al.
The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles
Free Radic. Biol. Med.
(2008) Oxy radicals, lipid peroxidation and DNA damage
Toxicology
(2002)- et al.
Risk assessment of airborne fine particles and nanoparticles
Adv. Powder Technol.
(2010)
Respiratory toxicity of multi-wall carbon nanotubes
Toxicol. Appl. Pharm.
Malondialdehyde, a product of lipid peroxidation, is mutagenic in human cells
J. Biol. Chem.
Reactive oxygen species, antioxidants and the mammalian thioredoxin system
Free Radic. Biol. Med.
Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells
Toxicology
Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation
Toxicology
Induction of inflammatory responses in mice treated with cerium oxide nanoparticles by intratracheal instillation
J. Health Sci.
Carbon nanotubes show no sign of acute toxicity but induce intracellular reactive oxygen species in dependence on contaminants
Toxicol. Lett.
Differential ability of transition metals to induce pulmonary inflammation
Toxicol. Appl. Pharmacol.
Synthesis and UV shielding properties of calcia-doped ceria nanoparticles coated with amorphous silica
Solid State Ionics
Cerium and yttrium oxide nanoparticles are neuroprotective
Biochem. Biophys. Res. Commun.
Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO2 nanoparticles
Toxicology
Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles: differential responses related to surface properties
Toxicology
Preparation and characterization of CuO/CeO2 catalysts and their applications in low-temperature CO oxidation
Appl. Catal. A: Gen.
CeO2 nanoparticles induce DNA damage towards human dermal fibroblasts in vitro
Nanotoxicology
Particle characteristics responsible for effects on human lung epithelial cells
Res. Rep. Health Eff. Inst.
Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: role of lipid peroxidation DNA damage, and repair
Lamgenbecks. Arch. Surg.
Ultrafine particle deposition and clearance in the healthy and obstructed lung
Am. J. Respir. Crit. Care Med.
Hierarchically meso structured doped CeO2 with potential for solar-cell use
Nat. Mater.
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