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Inhalation Toxicology
International Forum for Respiratory Research
Volume 33, 2021 - Issue 2
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Research Articles

Lung toxicity and gene expression changes in response to whole-body inhalation exposure to cellulose nanocrystal in rats

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Pages 66-80 | Received 30 Nov 2020, Accepted 27 Jan 2021, Published online: 18 Feb 2021
 

Abstract

Objective

Human exposure to cellulose nanocrystal (CNC) is possible during the production and/or use of products containing CNC. The objectives of the current study were to determine the lung toxicity of CNC and the underlying molecular mechanisms of the toxicity.

Methods

Rats were exposed to air or CNC (20 mg/m3, six hours/day, 14 d) by whole-body inhalation and lung toxicity and global gene expression profile were determined.

Results

Significant increases in lactate dehydrogenase activity, pro-inflammatory cytokine levels, phagocyte oxidant production, and macrophage and neutrophil counts were detected in the bronchoalveolar lavage cells or fluid from the CNC exposed rats. Mild lung histological changes, such as the accumulation of macrophages and neutrophils, were detected in the CNC exposed rats. Gene expression profiling by next generation sequencing identified 531 genes whose expressions were significantly different in the lungs of the CNC exposed rats, compared with the controls. Bioinformatic analysis of the lung gene expression data identified significant enrichment in several biological functions and canonical pathways including those related to inflammation (cellular movement, immune cell trafficking, inflammatory diseases and response, respiratory disease, complement system, acute phase response, leukocyte extravasation signaling, granulocyte and agranulocyte adhesion and diapedesis, IL-10 signaling, and phagosome formation and maturation) and oxidative stress (NRF2-mediated oxidative stress response, production of nitric oxide and reactive oxygen species in macrophages, and free radical scavenging).

Conclusion

Our data demonstrated that inhalation exposure of rats to CNC resulted in lung toxicity mediated mainly through the induction of inflammation and oxidative stress.

Acknowledgements

The authors thank Howard Leonard and Aleks Stefaniak (NIOSH Morgantown, WV) for assistance with inhalation exposure of rats and for critical review of the manuscript, respectively.

Disclosure statement

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention.

Additional information

Funding

Funding for this project was provided by Nanotechnology Research Center (NIOSH) [Project Numbers 921044E and 93909NA].

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