posted on 2022-01-19, 20:33authored byPawel Lorkiewicz, Rachel Keith, Jordan Lynch, Lexiao Jin, Whitney Theis, Tatiana Krivokhizhina, Daniel Riggs, Aruni Bhatnagar, Sanjay Srivastava, Daniel J. Conklin
Despite the increasing
popularity of e-cigarettes, their long-term
health effects remain unknown. In animal models, exposure to e-cigarette
has been reported to result in pulmonary and cardiovascular injury,
and in humans, the acute use of e-cigarettes increases heart rate
and blood pressure and induces endothelial dysfunction. In both animal
models and humans, cardiovascular dysfunction associated with e-cigarettes
has been linked to reactive aldehydes such as formaldehyde and acrolein
generated in e-cigarette aerosols. These aldehydes are known products
of heating and degradation of vegetable glycerin (VG) present in e-liquids.
Here, we report that in mice, acute exposure to a mixture of propylene
glycol:vegetable glycerin (PG:VG) or to e-cigarette-derived aerosols
significantly increased the urinary excretion of acrolein and glycidol
metabolites3-hydroxypropylmercapturic acid (3HPMA) and 2,3-dihydroxypropylmercapturic
acid (23HPMA)as measured by UPLC-MS/MS. In humans, the use
of e-cigarettes led to an increase in the urinary levels of 23HPMA
but not 3HPMA. Acute exposure of mice to aerosols derived from PG:13C3-VG significantly increased the 13C3 enrichment of both urinary metabolites 13C3-3HPMA and 13C3-23HPMA. Our stable
isotope tracing experiments provide further evidence that thermal
decomposition of vegetable glycerin in the e-cigarette solvent leads
to generation of acrolein and glycidol. This suggests that the adverse
health effects of e-cigarettes may be attributable in part to these
reactive compounds formed through the process of aerosolizing nicotine.
Our findings also support the notion that 23HPMA, but not 3HPMA, may
be a relatively specific biomarker of e-cigarette use.