An assessment of vaping-induced inflammation and toxicity: A feasibility study using a 2-stage zebrafish and mouse platform

Onyenwoke, Rob U.; Leung, TinChung; Huang, Xiaoyan; Parker, De’Jana; Alhadyan, Shatha K.; Sivaraman, Vijay

doi:10.1016/j.fct.2022.112923

Cited by 7 publications

(14 citation statements)

References 114 publications

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“…While not an obvious in vivo model to study the effects of vaping, the zebrafish model has provided a strong platform for our previous studies and has been used to perform inflammation and toxicity assays. ,, In fact, while using zebrafish embryos, we have previously demonstrated developmental effects and pro-inflammatory response, as indicated by a neutrophil migration response, after treatments with many of the same vaped flavored e-liquids utilized above (VT, “mint”, and “menthol”), with the VT, “mint” and “menthol” e-liquids all inducing pro-inflammatory responses . However, higher concentrations (e.g., 0.0375% “mint”) of e-liquid in the zebrafish medium reduced the survival of the exposed embryos with doses higher than 0.075, 0.05, and 0.025% for “menthol”, “VT” and “mint”, respectively, demonstrated as lethal for zebrafish embryo survival (Onyenwoke et al 2022) . However, these earlier studies did inform us of appropriate e-liquid concentrations (0.05 and 0.15%) for further assays, as described below.…”

Section: Resultsmentioning

confidence: 99%

GC/HRMS Analysis of E-Liquids Complements In Vivo Modeling Methods and can Help to Predict Toxicity

Walker-Franklin,

Onyenwoke,

Leung

et al. 2024

ACS Omega

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Tobacco smoking is a major risk factor for disease development, with the user inhaling various chemicals known to be toxic. However, many of these chemicals are absent before tobacco is "burned". Similar, detailed data have only more recently being reported for the e-cigarette with regards to chemicals present before and after the e-liquid is "vaped." Here, zebrafish were dosed with vaped e-liquids, while C57-BL/6J mice were vaped using nose-cone only administration. Preliminary assessments were made using e-liquids and GC/ HRMS to identify chemical signatures that differ between unvaped/vaped and flavored/unflavored samples. Oxidative stress and inflammatory immune cell response assays were then performed using our in vivo models. Chemical signatures differed, e.g., between unvaped/vaped samples and also between unflavored/flavored e-liquids, with known chemical irritants upregulated in vaped and unvaped flavored e-liquids compared with unflavored e-liquids. However, when possible respiratory irritants were evaluated, these agents were predominantly present in only the vaped e-liquid. Both oxidative stress and inflammatory responses were induced by a menthol-flavored but not a tobacco-flavored e-liquid. Thus, chemical signatures differ between unvaped versus vaped e-liquid samples and also between unflavored versus flavored e-liquids. These flavors also likely play a significant role in the variability of e-liquid characteristics, e.g., pro-inflammatory and/or cytotoxic responses.

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Section: Resultsmentioning

confidence: 99%

GC/HRMS Analysis of E-Liquids Complements In Vivo Modeling Methods and can Help to Predict Toxicity

Walker-Franklin,

Onyenwoke,

Leung

et al. 2024

ACS Omega

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“…Studies elucidating multiple aspects of the effects of these products will be necessary and must include animal modeling, especially with younger animal age groups. These types of studies are now being performed, ,, in particular with young mouse cohorts, − to analyze the effects of vaping on overall health. Of note, the possible neurotoxicity associated with e-cigarette use and particularly during neurodevelopment has more recently become a topic being addressed by a small but growing number of researchers through the use of animal studies. − The impact of maternal exposure to vaped aerosols on offspring cognitive function has also been evaluated using animal models and demonstrated short-term memory deficits, reduced anxiety, and hyperactivity in offspring. , These early data are extremely troubling due to the growing popularity of the e-cigarette among vulnerable populations, for example, pregnant women and adolescents (see Ruszkiewicz et al for a thorough review).…”

Section: Discussionmentioning

confidence: 99%

E-cigarette Flavors, Sensory Perception, and Evoked Responses

Alhadyan

Sivaraman

Onyenwoke

2022

Chem. Res. Toxicol.

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The chemosensory experiences evoked by flavors encompass a number of unique sensations that include olfactory stimuli (smell), gustatory stimuli (taste, i.e., salty, sweet, sour, bitter, and umami (also known as “savoriness”)), and chemesthesis (touch). As such, the responses evoked by flavors are complex and, as briefly stated above, involve multiple perceptive mechanisms. The practice of adding flavorings to tobacco products dates back to the 17th century but is likely much older. More recently, the electronic cigarette or “e-cigarette” and its accompanying flavored e-liquids emerged on to the global market. These new products contain no combustible tobacco but often contain large concentrations (reported from 0 to more than 50 mg/mL) of nicotine as well as numerous flavorings and/or flavor chemicals. At present, there are more than 400 e-cigarette brands available along with potentially >15,000 different/unique flavored products. However, surprisingly little is known about the flavors/flavor chemicals added to these products, which can account for >1% by weight of some e-liquids, and their resultant chemosensory experiences, and the US FDA has done relatively little, until recently, to regulate these products. This article will discuss e-cigarette flavors and flavor chemicals, their elicited responses, and their sensory effects in some detail.

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“…Exposure to e-cigarette aerosols, which contain reactive oxygen species (ROS) and harmful compounds, triggers oxidative stress within zebrafish tissues. This results in elevated oxidative stress markers and the activation of inflammatory pathways [ 105 , 106 , 107 ]. Additionally, e-cigarette exposure in zebrafish embryos has been associated with DNA damage and programmed cell death, known as apoptosis.…”

Section: Cellular and Molecular Mechanisms Of E-cigarette Toxicity In...mentioning

confidence: 99%

“…Real-time imaging techniques like confocal or light-sheet microscopy capture dynamic processes in zebrafish embryos exposed to e-cigarette aerosols, providing visual insights into developmental changes [ 150 ]. This technology has been widely used in studies focused on electronic cigarette effects on physiological processes and organogenesis [ 107 ].…”

Section: Pushing the Boundaries Of E-cigarette Research With Zebrafis...mentioning

confidence: 99%

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Zebrafish (Danio rerio) as a Model for the Study of Developmental and Cardiovascular Toxicity of Electronic Cigarettes

Hussen,

Aakel,

Shaito

et al. 2023

IJMS

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The increasing popularity of electronic cigarettes (e-cigarettes) as an alternative to conventional tobacco products has raised concerns regarding their potential adverse effects. The cardiovascular system undergoes intricate processes forming the heart and blood vessels during fetal development. However, the precise impact of e-cigarette smoke and aerosols on these delicate developmental processes remains elusive. Previous studies have revealed changes in gene expression patterns, disruptions in cellular signaling pathways, and increased oxidative stress resulting from e-cigarette exposure. These findings indicate the potential for e-cigarettes to cause developmental and cardiovascular harm. This comprehensive review article discusses various aspects of electronic cigarette use, emphasizing the relevance of cardiovascular studies in Zebrafish for understanding the risks to human health. It also highlights novel experimental approaches and technologies while addressing their inherent challenges and limitations.

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An assessment of vaping-induced inflammation and toxicity: A feasibility study using a 2-stage zebrafish and mouse platform

Cited by 7 publications

References 114 publications

GC/HRMS Analysis of E-Liquids Complements In Vivo Modeling Methods and can Help to Predict Toxicity

GC/HRMS Analysis of E-Liquids Complements In Vivo Modeling Methods and can Help to Predict Toxicity

E-cigarette Flavors, Sensory Perception, and Evoked Responses

Zebrafish (Danio rerio) as a Model for the Study of Developmental and Cardiovascular Toxicity of Electronic Cigarettes

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