Pharmacological and physiological response in Apoe^−/− mice exposed to cigarette smoke or e-cigarette aerosols

Abstract

Objective

Electronic cigarettes (e-cigs) are popular nicotine delivery devices, yet the health effects remain unclear. To determine equivalent biomarkers, we characterized the immediate response in Apoe^−/− mice exposed to tank/box-mod e-cig (e-cig_tank), pod e-cig (e-cig_pod), or cig smoke.

Materials and methods

Reproducible puff profiles were generated for each aerosol and delivered to Apoe^−/− mice via a nose-only exposure system. Serum cotinine levels were quantified at various time points through ELISA and utilized to model cotinine pharmacokinetics. In addition, particle size measurements and mouse respiratory function were characterized to calculate particle dosimetry.

Results and discussion

Cig and e-cig_tank particles were lognormally distributed with similar count median diameters (cig: 178 ± 2, e-cig_tank: 200 ± 34nm), while e-cig_pod particles were bimodally distributed and smaller (116 ± 13 and 13.3 ± 0.4 nm). Minute volumes decreased with cig exposure (5.4 ± 2.7 mL/min) compared to baseline (90.8 ± 11.6 mL/min), and less so with e-cig_tank (45.2 ± 9.2 mL/min) and e-cig_pod exposures (58.6 ± 6.8 mL/min), due to periods of apnea in the cig exposed groups. Cotinine was absorbed and eliminated most rapidly in the e-cig_pod group ($t_{\mathit{max}}$ = 14.5; $t_{1/2}^{\mathrm{\text{'}}}$ = 51.9 min), whereas cotinine was absorbed (cig: 50.4, e-cig_tank: 40.1 min) and eliminated (cig: 104.6, e-cig_tank: 94.1 min) similarly in the cig and e-cig_tank groups. For exposure times which equate the area under the cotinine-concentration curve, ∼6.4× (e-cig_tank) and 4.6× (e-cig_pod) more nicotine deposited in e-cig compared to cig exposed mice.

Conclusions

This study provides a basis for incorporating cotinine pharmacokinetics into preclinical exposure studies, allowing for longitudinal studies of structural and functional changes due to exposure.

IMPACT STATEMENT

This study highlights that pod e-cigs deliver smaller particles than tank/box-mode e-cigs and cig smoke. Minute volumes were substantially reduced in cig smoke-exposed mice, due to periods of apnea, whereas only expiration times increased in the e-cig-exposed groups. More particles deposit in e-cig exposed mice, compared to the cig group, for equivalent daily area under the cotinine concentration curve.

Keywords:

• Pod e-cig
• dosimetry
• respiratory rate
• particle size
• pharmacokinetics
• JUUL
• heart rate

Acknowledgments

The authors would like to thank Emma Lloyd and Benjamin Sylvanus of Northeastern University and Stephanie Rosenbaum of SCIREQ Inc. for invaluable assistance in animal exposure.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by NIH/NHLBI R03 HL142472, NSF GRFP Fellowship (Y. Farra), and Northeastern University Tier 1 Grant.