Predicting molecular mechanisms, pathways, and health outcomes induced by Juul e-cigarette aerosol chemicals using the Comparative Toxicogenomics Database

https://doi.org/10.1016/j.crtox.2021.08.001Get rights and content
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Highlights

  • Vaping chemicals of Juul aerosols were analyzed using CTD.

  • CTD can be used to predict disease associations of Juul aerosol chemicals.

  • Predictive pathways that relate vaping aerosols to diseases are described.

Abstract

There is a critical need to understand the health risks associated with vaping e-cigarettes, which has reached epidemic levels among teens. Juul is currently the most popular type of e-cigarette on the market. Using the Comparative Toxicogenomics Database (CTD; http://ctdbase.org), a public resource that integrates chemical, gene, phenotype and disease data, we aimed to analyze the potential molecular mechanisms of eight chemicals detected in the aerosols generated by heating Juul e-cigarette pods: nicotine, acetaldehyde, formaldehyde, free radicals, crotonaldehyde, acetone, pyruvaldehyde, and particulate matter. Curated content in CTD, including chemical-gene, chemical-phenotype, and chemical-disease interactions, as well as associated phenotypes and pathway enrichment, were analyzed to help identify potential molecular mechanisms and diseases associated with vaping. Nicotine shows the most direct disease associations of these chemicals, followed by particulate matter and formaldehyde. Together, these chemicals show a direct marker or mechanistic relationship with 400 unique diseases in CTD, particularly in the categories of cardiovascular diseases, nervous system diseases, respiratory tract diseases, cancers, and mental disorders. We chose three respiratory tract diseases to investigate further, and found that in addition to cellular processes of apoptosis and cell proliferation, prioritized phenotypes underlying Juul-associated respiratory tract disease outcomes include response to oxidative stress, inflammatory response, and several cell signaling pathways (p38MAPK, NIK/NFkappaB, calcium-mediated).

Abbreviations

A
acetaldehyde
AC
acetone
C
crotonaldehyde
CGPD
chemical-gene-phenotype-disease
COPD
chronic obstructive pulmonary disease
Cr
chromium
CTD
Comparative Toxicogenomics Database
F
formaldehyde
FR
free radicals
M
marker/mechanism relationship
MIE
molecular initiating event
MOA
mode-of-action
Mn
manganese
N
nicotine
NAFFCAPP
nicotine, acetaldehyde, formaldehyde, free radicals, crotonaldehyde, acetone, pyruvaldehyde, and particulate matter chemical mixture
NAFP
nicotine, acetaldehyde, formaldehyde, particulate matter chemical mixture
nAChR
nicotinic acetylcholine receptor
Ni
nickel
P
pyruvaldehyde
Pb
lead
PM
particulate matter
ROS
reactive oxygen species
Zn
zinc

Keywords

E-cigarettes
Vaping
Juul
Respiratory disease
Database
Environmental exposure

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