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dc.contributor.authorStaal, Yvonne C M
dc.contributor.authorLi, Yixuan
dc.contributor.authorGerber, Lora-Sophie
dc.contributor.authorFokkens, Paul
dc.contributor.authorCremers, Hans
dc.contributor.authorCassee, Flemming R
dc.contributor.authorTalhout, Reinskje
dc.contributor.authorWesterink, Remco H S
dc.contributor.authorHeusinkveld, Harm J
dc.date.accessioned2022-09-05T10:45:01Z
dc.date.available2022-09-05T10:45:01Z
dc.date.issued2022-09-02
dc.identifier.pmid36053669
dc.identifier.doi10.1080/08958378.2022.2118911
dc.identifier.urihttp://hdl.handle.net/10029/626066
dc.description.abstractThe most direct effects of inhaled harmful constituents are the effects on the airways. However, inhaled compounds can be rapidly absorbed and subsequently result in systemic effects. For example, e-cigarette vapor has been shown to evoke local effects in the lung, although little is known about subsequent effects in secondary target organs such as the brain. Traditionally, such effects are tested using in vivo models. As an alternative, we have combined two in vitro systems, which are Air-Liquid-Interface (ALI) cultured alveolar cells (A549) and rat primary cortical cultures grown on multi-well microelectrode arrays. This allows us to assess the neurological effects of inhaled compounds. We have used exposure to e-cigarette vapor, containing nicotine, menthol, or vanillin to test the model. Our results show that ALI cultured A549 cells respond to the exposure with the production of cytokines (IL8 and GROalpha). Furthermore, nicotine, menthol, and vanillin were found on the basolateral side of the cell culture, which indicates their translocation. Upon transfer of the basolateral medium to the primary cortical culture, exposure-related changes in spontaneous electrical activity were observed correlating with the presence of e-liquid components in the medium. These clear neuromodulatory effects demonstrate the feasibility of combining continuous exposure of ALI cultured cells with subsequent exposure of neuronal cells to assess neurotoxicity. Although further optimization steps are needed, such a combination of methods is important to assess the neurotoxic effects of inhaled compounds realistically. As such, an approach like this could play a role in future mechanism-based risk assessment strategies.en_US
dc.language.isoenen_US
dc.subjectIn vitroen_US
dc.subjectair-liquid interfaceen_US
dc.subjecthazard assessmenten_US
dc.subjectmicroelectrode arrayen_US
dc.titleNeuromodulatory and neurotoxic effects of e-cigarette vapor using a realistic exposure method.en_US
dc.typeArticleen_US
dc.identifier.eissn1091-7691
dc.identifier.journalInhalation toxicology 2023 ;35(3-4):76-85en_US
dc.source.journaltitleInhalation toxicology
dc.source.beginpage1
dc.source.endpage10
dc.source.countryEngland


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