An e-cigarette aerosol generation, animal exposure and toxicants quantification system to characterize in vivo nicotine kinetics in arterial and venous blood

Zhang, J.; Xue, M.; Pan, R.; Zhu, Y.; Zhang, Z.; Cheng, H.; Björkegren, J. L. M.; Chen, J.; Shi, Z.; Hao, K.

doi:10.1101/2022.10.12.511981

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bioRxiv · 10.1101/2022.10.12.511981

An e-cigarette aerosol generation, animal exposure and toxicants quantification system to characterize in vivo nicotine kinetics in arterial and venous blood

Zhang, J.·Xue, M.·Pan, R.·Zhu, Y.·Zhang, Z.·Cheng, H.·Björkegren, J. L. M.·Chen, J.·Shi, Z.·Hao, K.

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Abstract

The increasing e-cigarette use worldwide presents an urgent need to characterize their nicotine delivery property, brain stimulation and potential long-term health effects. We constructed an end-to-end system enabling combustible-cigarette (c-cigarette) and e-cigarette aerosol generation, animal exposure, and effect assessment. The system consists of (1) a 10-channel aerosol generator resembling human smoking/vaping scenarios, (2) nose-only and whole-body exposure chambers suitable for long- or short-duration studies, (3) a lab protocol for animal exposure and collecting arterial and venous blood <1 minute after the exposure, and (4) chromatograph and mass spectrometry to quantify nicotine concentrations in aerosol and biospecimens. We applied the system in a proof-of-principle study characterizing in vivo nicotine delivery after e-cigarette aerosol inhalation. Groups of Sprague-Dawley rats were exposed to e-cigarette aerosols for 1, 2 and 4 minutes, respectively. Arterial and venous blood samples were collected immediately after the exposure. We also directly compared nose-only and whole-body exposure approaches. After nose-only e-cigarette aerosol exposure, the nicotine concentration in arterial blood was substantially higher (11.32 ng/mL in average) than in veins. Similar arterio-venous concentration difference was observed in whole-body exposure experiments. In summary, we described a complete system ideal for e- and c-cigarette in vivo nicotine kinetics and long-term health research. Our findings highlight arterial blood as the suitable bio-specimen for e-cigarette nicotine delivery studies. HighlightO_LIWe constructed a combustible- and e-cigarette aerosol generation - exposure - effect assessment system resembling real world human smoking/vaping scenarios. C_LIO_LIProof-of-principle study characterized in vivo nicotine delivery from e-cigarette aerosol to arterial and venous blood at high temporal resolution. C_LIO_LIAfter exposure, the nicotine concentration was substantially higher (11.32 ng/mL) in arterial blood than in veins. C_LIO_LIOur results suggest arterial blood as the suitable bio-specimen to study nicotine delivery and brain stimulation. C_LI

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Zhang, J., Xue, M., Pan, R., Zhu, Y., Zhang, Z., Cheng, H., Björkegren, J. L. M., Chen, J., Shi, Z., Hao, K.. 2022-10-17. An e-cigarette aerosol generation, animal exposure and toxicants quantification system to characterize in vivo nicotine kinetics in arterial and venous blood. https://doi.org/10.1101/2022.10.12.511981

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