PMID- 36692165
OWN - NLM
STAT- MEDLINE
DCOM- 20230316
LR  - 20240302
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 324
IP  - 3
DP  - 2023 Mar 1
TI  - Menthol flavoring in e-cigarette condensate causes pulmonary dysfunction and 
      cytotoxicity in precision cut lung slices.
PG  - L345-L357
LID - 10.1152/ajplung.00222.2022 [doi]
AB  - E-cigarette consumption is under scrutiny by regulatory authorities due to 
      concerns about product toxicity, lack of manufacturing standards, and increasing 
      reports of e-cigarette- or vaping-associated acute lung injury. In vitro studies 
      have demonstrated cytotoxicity, mitochondrial dysfunction, and oxidative stress 
      induced by unflavored e-cigarette aerosols and flavoring additives. However, 
      e-cigarette effects on the complex lung parenchyma remain unclear. Herein, the 
      impact of e-cigarette condensates with or without menthol flavoring on 
      functional, structural, and cellular responses was investigated using mouse 
      precision cut lung slices (PCLS). PCLS were exposed to e-cigarette condensates 
      prepared from aerosolized vehicle, nicotine, nicotine + menthol, and menthol 
      e-fluids at doses from 50 to 500 mM. Doses were normalized to the glycerin 
      content of vehicle. Video-microscopy of PCLS revealed impaired contractile 
      responsiveness of airways to methacholine and dampened ciliary beating following 
      exposure to menthol-containing condensates at concentrations greater than 300 mM. 
      Following 500 mM menthol-containing condensate exposure, epithelial exfoliation 
      in intrabronchial airways was identified in histological sections of PCLS. 
      Measurement of lactate dehydrogenase release, mitochondrial 
      water-soluble-tetrazolium salt-1 conversion, and glutathione content supported 
      earlier findings of nicotine or nicotine + menthol e-cigarette-induced 
      dose-dependent cytotoxicity and oxidative stress responses. Evaluation of PCLS 
      metabolic activity revealed dose-related impairment of mitochondrial oxidative 
      phosphorylation and glycolysis after exposure to menthol-containing condensates. 
      Taken together, these data demonstrate prominent menthol-induced pulmonary 
      toxicity and impairment of essential physiological functions in the lung, which 
      warrants concerns about e-cigarette consumer safety and emphasizes the need for 
      further investigations of molecular mechanisms of toxicity and menthol effects in 
      an experimental model of disease.
FAU - Herbert, Julia
AU  - Herbert J
AUID- ORCID: 0000-0001-5676-2512
AD  - Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, 
      Rutgers University, Piscataway, New Jersey, United States.
FAU - Kelty, Jacklyn S
AU  - Kelty JS
AUID- ORCID: 0000-0001-8540-874X
AD  - Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, 
      Rutgers University, Piscataway, New Jersey, United States.
FAU - Laskin, Jeffrey D
AU  - Laskin JD
AD  - Department of Environmental and Occupational Health and Justice, School of Public 
      Health, Rutgers University, Piscataway, New Jersey, United States.
FAU - Laskin, Debra L
AU  - Laskin DL
AUID- ORCID: 0000-0003-1832-7311
AD  - Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, 
      Rutgers University, Piscataway, New Jersey, United States.
FAU - Gow, Andrew J
AU  - Gow AJ
AUID- ORCID: 0000-0003-0876-5158
AD  - Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, 
      Rutgers University, Piscataway, New Jersey, United States.
LA  - eng
SI  - figshare/10.6084/m9.figshare.20323689.v2
GR  - P30 ES005022/ES/NIEHS NIH HHS/United States
GR  - T32 ES007148/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230124
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 6M3C89ZY6R (Nicotine)
RN  - 1490-04-6 (Menthol)
RN  - 0 (Flavoring Agents)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Nicotine/toxicity
MH  - *Electronic Nicotine Delivery Systems
MH  - Menthol/toxicity
MH  - Respiratory Aerosols and Droplets
MH  - Lung
MH  - Flavoring Agents/toxicity
PMC - PMC10026991
OTO - NOTNLM
OT  - PCLS
OT  - e-cigarettes
OT  - lung toxicity
OT  - menthol
OT  - nicotine
OT  - precision cut lung slices
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2023/01/25 06:00
MHDA- 2023/03/17 06:00
PMCR- 2024/03/01
CRDT- 2023/01/24 08:02
PHST- 2023/01/25 06:00 [pubmed]
PHST- 2023/03/17 06:00 [medline]
PHST- 2023/01/24 08:02 [entrez]
PHST- 2024/03/01 00:00 [pmc-release]
AID - L-00222-2022 [pii]
AID - 10.1152/ajplung.00222.2022 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2023 Mar 1;324(3):L345-L357. doi: 
      10.1152/ajplung.00222.2022. Epub 2023 Jan 24.