Neurobehavioral effects of 1,2-propanediol in zebrafish (Danio rerio)

Abstract

The use of electronic cigarettes (e-cigarettes) is increasing despite insufficient information concerning their long-term effects, including the effects of maternal e-cigarette use on pre- and postnatal development. Our previous study demonstrated that developmental exposure to 1,2-propanediol (a principal component of e-cigarette liquid) affected early development of zebrafish, causing reduced growth, deformities, and hyperactive swimming behavior in larvae. The current study extends assessment of the developmental toxicity of 1,2-propanediol by examining additional long-term behavioral effects. We demonstrate that embryonic/larval exposure of zebrafish to 1,2-propanediol (0.625% or 1.25%) not only affected behavioral parameters in the larvae, but also caused persisting behavioral effects in adults after early developmental exposure. Additional parameters, including neural and vascular development in larvae, stress response in adults, and concentration of neurotransmitters dopamine and serotonin in adult brain were examined, in order to explain the behavioral differences. These additional assessments did not find 1,2-propanediol exposure to significantly affect Tg(Neurog1:GFP) or the transcript abundance of neural genes (Neurog1, Ascl1a, Elavl3, and Lef1). Vascular development was not found to be affected by 1,2-propanediol exposure, as inferred from experiments with Tg(Flk1:eGFP) zebrafish; however, transcript abundance of vascular genes (Flk1, Vegf, Tie-2, and Angpt1) was decreased. No statistically significant changes were noted for plasma cortisol or brain neurotransmitters in adult fish. Lastly, analysis of gene transcripts involved with 1,2-propanediol metabolism (Adh5, Aldh2.1, and Ldha) showed an increase in Adh5 transcript. This is the first study to demonstrate that developmental exposure to 1,2-propanediol has long-term neurobehavioral consequences in adult zebrafish, showing that e-cigarettes contain substances potentially harmful to neurodevelopment.

Impact of Nicotine Replacement and Electronic Nicotine Delivery Systems on Fetal Brain Development

“…Massarsky et al evaluated the neurobehavioral impact of 1,2-PDO toxicity in a zebrafish model, assessing two different concentrations (0.625% and 1.25%). In this study, 1,2-PDO was associated to a hyperactive swimming pattern, concluding that these substances may cause long-term neurobehavioral consequences [72].…”

An updated overview of e-cigarette impact on human health

“…In vitro, aerosols from glycerol only-containing refills showed cytotoxicity in A549 and human embryonic stem cells, even at a low battery output voltage [ 59 ]. PG was also found to affect early neurodevelopment in a zebrafish model [ 60 ]. Another important issue is that, under heating conditions PG can produce acetaldehyde or formaldehyde (119.2 or 143.7 ng/puff at 20 W, respectively, on average), while glycerol can also generate acrolein (53.0, 1000.0 or 5.9 ng/puff at 20 W, respectively, on average), all carbonyls with a well-documented toxicity [ 61 ].…”

Developmental toxicity and neurotoxicity assessment of R-, S-, and RS-propylene glycol enantiomers in zebrafish (Danio rerio) larvae

“…Usually, animals exposed to hazardous chemicals can change their behavior and these changes may affect their survival, growth, and reproduction (Wang et al, 2018). Previous study has been reported that embryonic exposure to PG can result in behavioral changes in zebra sh larvae (Massarsky et al, 2018). In the present study, we found that embryonic exposure to R-, S-, and RS-PG of high doses could signi cantly induce the locomotor hyperactivity of zebra sh larvae, demonstrating that R-, S-, and RS-PG of high doses could cause the neurodevelopmental effect in zebra sh larvae.…”

“…PG has very low toxicity and is considered to be a non-toxic or non-carcinogenic compound for adults (Zaripov et al, 2020). However, newborns and infants are specially susceptible to the effects of PG (Massarsky et al, 2018). In the present study, our results showed that R-, S-, and RS-PG enantiomers of high doses can exhibit the neurotoxicity and ocular developmental toxicity in zebra sh larvae, indicating that R-, S-, and RS-PG exposures of high doses have the potential neurotoxicity and ocular developmental toxicity for infants and toddlers.…”

“…Several studies have examined the toxicity of RS-PG in the context of repeated exposure to these preparations. For instance, embryonic exposure to 0.625% or 1.25% RS-PG not only affect behavioral parameters in the zebra sh (Danio rerio) larvae, but cause persisting behavioral effects in adults (Massarsky et al, 2018). Besides, parenteral administration of RS-PG can cause certain behavioral effects in rodents, including locomotor suppression and anxiolytic effects (Lin et al, 1998;Silva & Elisabetsky, 2001;Harris et al, 2018).…”