Pulmonary toxicity and RNA sequencing analyses of mouse in response to exposure to cellulose nanofibrils

Abstract

Objective

The growing applications of nanocelluloses in the fields of advanced nanocomposites, electronics, and medical devices necessitate investigation of their potential adverse effects on human health. The lungs are the primary and the most important route for the entry of nanocelluloses into the human body in occupational settings. However, data on the pulmonary toxicity of cellulose nanofibrils (CNFs) and its molecular mechanism are limited. This study investigated the pulmonary toxicity of CNFs and its genomic expression using the RNA sequencing approach.

Materials and methods

Female C57BL/6 mice were administered CNFs at 50 μg/mouse by oropharyngeal aspiration. Samples were collected at 3 and 14 days after exposure to CNFs (DAEC).

Results

At three DAEC, the microscopic sections of lungs revealed a significant inflammatory response. In terms of gene expression alterations, 94 genes were up-regulated, and 107 genes were down-regulated. Most of these differentially expressed genes were involved in the inflammatory and immune responses, including chemokines, NK cells, killer cell lectin-like receptors, CD antigens, T cell-specific GTPases, immunity-related GTPase family M members, and interferon-induced proteins encoding genes. However, only 9 and 26 genes at 14 DAEC were significantly up- and down-regulated, respectively.

Conclusions

The pathological analysis of lung sections and the analysis of sequencing data suggested that the homeostasis of mice lungs was restored at 14 DAEC. The findings of this study provide insights into the pulmonary toxicity, and underlying toxicological mechanisms, caused by exposure to CNFs, and are useful for the assessment of the potential toxicity of nanocelluloses.

Keywords:

• Cellulose nanofibrils
• nanotoxicology
• gene regulation
• next-generation screening approaches
• in vivo study

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was financially supported by The Talents Project for Harbin Science and Technology Innovation [Project No. 2016RAXXJ006] and the China Postdoctoral Science Foundation [Project No. 2017M611341].