Gender differences in murine pulmonary responses elicited by cellulose nanocrystals.
Cellulose-based materials have been used for centuries to manufacture different goods derived from forestry and agricultural sources. In the growing field of nanocellulose applications, its uniquely engineered properties are instrumental for inventive products coming to competitive markets. Due to their high aspect ratio and stiffness, it is speculated that cellulose nanocrystals (CNC) may cause similar pulmonary toxicity as carbon nanotubes and asbestos, thus posing a potential negative impact on public health and the environment.



The present study was undertaken to investigate the pulmonary outcomes induced by repeated exposure to respirable CNC. C57BL/6 female and male mice were exposed by pharyngeal aspiration to CNC (40 μg/mouse) 2 times a week for 3 weeks. Several biochemical endpoints and pathophysiological outcomes along with gene expression changes were evaluated and compared in the lungs of male and female mice.



Exposure to respirable CNC caused pulmonary inflammation and damage, induced oxidative stress, elevated TGF-β and collagen levels in lung, and impaired pulmonary functions. Notably, these effects were markedly more pronounced in females compared to male mice. Moreover, sex differences in responses to pulmonary exposure to CNC were also detected at the level of global mRNA expression as well as in inflammatory cytokine/chemokine activity.



Overall, our results indicate that there are considerable differences in responses to respirable CNC based on gender with a higher pulmonary toxicity observed in female mice.
Health Effects Laboratory Division, NIOSH, Exposure Assessment Branch, 1095 Willowdale Road, Morgantown, WV, 26505, USA. ats1@cdc.gov.|Department of Physiology & Pharmacology, School of Medicine/WVU, Morgantown, WV, USA. ats1@cdc.gov.
Anna A
AA
Shvedova
Health Effects Laboratory Division, NIOSH, Exposure Assessment Branch, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
Elena R
ER
Kisin
Health Effects Laboratory Division, NIOSH, Exposure Assessment Branch, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
Naveena
N
Yanamala
Health Effects Laboratory Division, NIOSH, Exposure Assessment Branch, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
Mariana T
MT
Farcas
Health Effects Laboratory Division, NIOSH, Exposure Assessment Branch, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
Autumn L
AL
Menas
Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, ON, K1A 0 K9, Canada.
Andrew
A
Williams
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
Philip M
PM
Fournier
Engineering and Controls Technology Branch, NIOSH/CDC, Morgantown, WV, USA.
Jeffrey S
JS
Reynolds
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Dmitriy W
DW
Gutkin
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
Alexander
A
Star
Forest Products Laboratory, USDA Forest Service, Madison, WI, USA.
Richard S
RS
Reiner
Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, ON, K1A 0 K9, Canada.
Sabina
S
Halappanavar
Free Radical Center, University of Pittsburgh, Pittsburgh, PA, USA.|Department of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
Valerian E
VE
Kagan
D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002482:Cellulose / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D010316:Particle Size; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012727:Sex Characteristics; D013047:Specific Pathogen-Free Organisms; D013499:Surface Properties
D000393:Air Pollutants; D015415:Biomarkers; D012333:RNA, Messenger; D002482:Cellulose
Cellulose; Gender differences; Inflammation; Oxidative stress; Pulmonary toxicity; mRNA expression