A mouse model for chronic intermittent electronic cigarette exposure exhibits nicotine pharmacokinetics resembling human vapers

Abstract

Electronic cigarettes (E-cig) use is increasing rapidly, particularly among youths. Animal models for E-cig exposure with pharmacokinetics resembling human E-cig users are lacking. We developed an E-cig aerosol exposure system for rodents and a chronic intermittent delivery method that simulates E-cig users who vape episodically during wakefulness and abstain during sleep. Mice were exposed to E-cig in a programmed schedule at very low, low, medium, or high doses defined by duration of each puff, number of puffs per delivery episode and frequency of episodes in the dark phase of a 12/12-h circadian cycle for 9 consecutive days. The plasma nicotine/cotinine levels and their time courses were determined using LC/MS-MS. We assessed the body weight, food intake and locomotor activity of Apolipoprotein E null (ApoE-/-) mice exposed to chronic intermittent E-cig aerosol. Plasma nicotine and cotinine levels were positively correlated with exposure doses. Nicotine and cotinine levels showed a circadian variation as they increased with time up to the maximum nicotine level of 21.8 ± 7.1 ng/mL during the daily intermittent E-cig exposure in the 12-h dark phase and then declined during the light phase when there was no E-cig delivery. Chronic E-cig exposure to ApoE-/mice decreased body weight, food intake and increased locomotion. Our rodent E-cig exposure system and chronic intermittent exposure method yield clinically relevant nicotine pharmacokinetics associated with behavioral and metabolic changes.

Electronic cigarettes cause alteration in cardiac structure and function in diet-induced obese mice

“…Our newly developed e-cigarettes aerosol exposure system can be programmed to deliver various doses of nicotine in rodents that yield plasma nicotine and cotinine levels in the ranges at very low, low, medium, and high [21]. Gold leaf tobacco (otherwise identical to Classic Tobacco) with 0% nicotine was used as an additional control to know if our findings are due to the nicotine in the e-cigarettes or to the vaporization of other non-nicotine e-cigarette ingredients.…”

E-Cigarette Use: Device Market, Study Design, and Emerging Evidence of Biological Consequences

“…Enhanced understanding of differences in usage patterns between new and more experienced EC users would facilitate better experimental design for studies distinguishing between acute and chronic exposure responses. The division between the two is already blurred; Shao et al [54] describe a "chronic" exposure as 12 h exposures consisting of two episodes per hour, for 12 weeks. The authors classified the exposure paradigm as chronic because it recapitulated the nicotine pharmacokinetics seen in EC users.…”

The fog, the attractive and the addictive: pulmonary effects of vaping with a focus on the contribution of each major vaping liquid constituent

“…Liquorice-, cinnamon-and tobacco-flavoured e-cigarette vapours prevent normal weight gain over time [23,83]. Mice exposed to cinnamon-flavoured electronic cigarette vapours containing nicotine before conception and during pregnancy give birth to smaller pups [84].…”

“…Mice exposed to cinnamon-flavoured electronic cigarette vapours containing nicotine before conception and during pregnancy give birth to smaller pups [84]. Adult mice exposed in utero to tobacco-flavoured e-cigarette vapours with nicotine show deficits in short-term memory, reduced anxiety and hyperactivity [60], as well as higher locomotor activity [83].…”

“…E-cigarette users have increased sputum and bronchial epithelial MUC5AC levels [90,91]. Male only [27,31,50,67,83,86,107,110] Female only [18, 22, 24, 25, 29, 30, 32, 33, 58-60, 65, 85, 108] Both [23,26,34,35,61,68,84,109] Unspecified [19,28,57] Studies assessing the combined but indistinguishable effects of the propylene glycol, glycerol, nicotine and flavours made more or less the same observations as those who investigated the specific compounds. However, without proper control groups, it remains difficult to assess which e-liquid constituent is responsible for the observed effects.…”