Premium
Cellular effects of nicotine salt‐containing e‐liquids
Author(s) -
Ghosh Arunava,
Beyazcicek Ozge,
Davis Eric S.,
Onyenwoke Rob U.,
Tarran Robert
Publication year - 2021
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.4060
Subject(s) - chemistry , cytoplasm , propidium iodide , cell signaling , endoplasmic reticulum , cytotoxic t cell , microbiology and biotechnology , cytotoxicity , intracellular , ceramide , nicotine , biochemistry , signal transduction , apoptosis , biology , programmed cell death , medicine , in vitro
“Pod‐based” e‐cigarettes such as JUUL are currently the most prevalent electronic nicotine delivery systems (ENDS) in the United States. JUUL‐type ENDS utilize nicotine salts protonated with benzoic acid rather than freebase nicotine. However, limited information is available on the cellular effects of these products. Cytoplasmic Ca 2+ is a universal second messenger that controls many cellular functions including cell growth and cell death. Of note, dysregulation of cell Ca 2+ homeostasis has been linked with several disease processes including autoimmune disease and several types of cancer. We exposed HEK293T cells and THP‐1 macrophage‐like cells to different JUUL e‐liquids. We evaluated their effects on cellular viability and Ca 2+ signaling by measuring fluorescence from calcein‐AM/propidium iodide and Fluo‐4, respectively. E‐liquid autofluorescence was used to look for e‐liquid permeation into cells. To identify the mechanisms behind the Ca 2+ responses, different inhibitors of Ca 2+ channels and phospholipase C signaling were used. JUUL e‐liquids caused significant cytotoxic effects, with “Mint” flavor being the most cytotoxic. The Mint flavored e‐liquid also caused a significant elevation in cytoplasmic Ca 2+ . Using autofluorescence, the permeation of JUUL e‐liquids into live cells was confirmed, indicating that intracellular organelles are directly exposed to e‐liquids. Further studies identified the endoplasmic reticulum as being the source of e‐liquid‐induced changes in cytoplasmic Ca 2+ . Nicotine salt‐based e‐liquids cause cytotoxicity and elevate cytoplasmic Ca 2+ , indicating that they can exert biological effects beyond what would be expected with nicotine alone. These effects are flavor‐dependent, and we propose that flavored e‐liquids be reassessed for potential lung toxicity.