Cellular effects of nicotine salt-containing e-liquids

Area of Science:

• Cell Biology
• Toxicology
• Nicotine Research

Background:

• Pod-based e-cigarettes (ENDS), particularly JUUL, are prevalent in the US.
• JUUL utilizes nicotine salts, differing from freebase nicotine ENDS.
• Limited data exists on the cellular impact of nicotine salt-based ENDS.

Purpose of the Study:

• To investigate the cellular effects of JUUL e-liquids on cell viability and calcium (Ca2+) signaling.
• To explore the mechanisms underlying JUUL e-liquid-induced cellular responses.
• To assess the flavor-dependent toxicity of JUUL e-liquids.

Main Methods:

• HEK293T and THP-1 cells were exposed to JUUL e-liquids.
• Cell viability was assessed using calcein-AM/propidium iodide.
• Ca2+ signaling was measured using Fluo-4 fluorescence.
• E-liquid permeation was detected via autofluorescence.
• Inhibitors of Ca2+ channels and phospholipase C were used to identify mechanisms.

Main Results:

• JUUL e-liquids induced significant cytotoxicity, with "Mint" flavor being the most potent.
• Exposure to JUUL e-liquids elevated cytoplasmic Ca2+ levels.
• E-liquid permeation into cells was confirmed, with the endoplasmic reticulum identified as the source of Ca2+ changes.
• Nicotine salt-based e-liquids demonstrated biological effects beyond nicotine alone.

Conclusions:

• Nicotine salt-based JUUL e-liquids exert flavor-dependent cytotoxicity and disrupt cellular Ca2+ homeostasis.
• The endoplasmic reticulum plays a role in mediating these Ca2+ responses.
• Flavored e-liquids warrant reassessment for potential lung toxicity due to observed cellular effects.