Metabolomics-based safety evaluation of acute exposure to electronic cigarettes in mice

Xiaoke Ren; Lisen Lin; Qinglin Sun; Tianyu Li; Mengqi Sun; Zhiwei Sun; Junchao Duan

doi:10.1016/j.scitotenv.2022.156392

Metabolomics-based safety evaluation of acute exposure to electronic cigarettes in mice

Sci Total Environ. 2022 Sep 15:839:156392. doi: 10.1016/j.scitotenv.2022.156392. Epub 2022 May 31.

Authors

Xiaoke Ren¹, Lisen Lin¹, Qinglin Sun¹, Tianyu Li¹, Mengqi Sun¹, Zhiwei Sun², Junchao Duan³

Affiliations

¹ Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China.
² Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China. Electronic address: zwsun@ccmu.edu.cn.
³ Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China. Electronic address: jcduan@ccmu.edu.cn.

PMID: 35660447
DOI: 10.1016/j.scitotenv.2022.156392

Abstract

Introduction: A growing number of epidemiological evidence reveals that electronic cigarettes (E-cigs) were associated with pneumonia, hypertension and atherosclerosis, but the toxicological evaluation and mechanism of E-cigs were largely unknown.

Objective: Our study was aimed to explore the adverse effects on organs and metabolomics changes in C57BL/6J mice after acute exposure to E-cigs.

Methods and results: Hematoxylin and eosin (H&E) staining found pathological changes in tissues after acute exposure to E-cigs, such as inflammatory cell infiltration, nuclear pyknosis, and intercellular interstitial enlargement. E-cigs could increase apoptosis-positive cells in a time-dependent way using Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Oxidative damage indicators of reactive oxygen species (ROS), malondialdehyde (MDA) and 4-hydroxynonena (4-HNE) were also elevated after E-cigs exposure. There was an increasing trend of total glycerol and cholesterol in serum, while the glucose and liver enzymes including alanine aminotransferase (ALT), aspartate transaminase (AST), gamma-glutamyltranspeptidase (γ-GT) had no significant change compared to that of control. Further, Q Exactive high field (HF) mass spectrometer was used to conduct metabolomics, which revealed that differential metabolites including l-carnitine, Capryloyl glycine, etc. Trend analysis showed the type of compounds that change over time. Pathway enrichment analysis indicated that E-cigs affected 24 metabolic pathways, which were mainly regulated amino acid metabolism, further affected the tricarboxylic acid (TCA) cycle. Additionally, metabolites-diseases network analysis found that the type 2 diabetes mellitus, propionic acidemia, defect in long-chain fatty acids transport and lung cancer may be related to E-cigs exposure.

Conclusions: Our findings provided important clues for metabolites biomarkers of E-cigs acute exposure and are beneficial for disease prevention.

Keywords: Acute exposure; Amino acid metabolism; E-cigs; Metabolomics; Tricarboxylic acid cycle.

MeSH terms

Animals
Diabetes Mellitus, Type 2*
Electronic Nicotine Delivery Systems*
Metabolomics
Mice
Mice, Inbred C57BL
Propionic Acidemia*