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Development of a Microscale Cell Culture Analog To Probe Naphthalene Toxicity
Abstract
Prediction of human response to drugs or chemicals is difficult as a result of the complexity of living organisms. We describe an in vitro model that can realistically and inexpensively study the adsorption, distribution, metabolism, elimination, and potential toxicity (ADMET) of chemicals. A microscale cell culture analog (microCCA) is a physical replica of the physiologically based pharmacokinetics (PBPK) model. Such a microfabricated device consists of a fluidic network of channels to mimic the circulatory system and chambers containing cultured mammalian cells representing key functions of animal "organ" systems. This paper describes the application of a two-cell system, four-chamber microCCA ("lung"-"liver"-"other tissue"-"fat") device for proof-of-concept study using naphthalene as a model toxicant. Naphthalene is converted into reactive metabolites (i.e., 1,2-naphthalenediol and 1,2-naphthoquinone) in the "liver" compartment, which then circulate to the "lung" depleting glutathione (GSH) in lung cells. Such microfabricated in vitro devices are potential human surrogates for testing chemicals and pharmaceutics for toxicity and efficacy.
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“For example, naphthalene was converted in the liver module into its reactive metabolites and transferred to the lung module, where it depleted cellular glutathione levels and caused the accumulation of hydrophobic compounds in the fat module (Viravaidya et al., 2004).”
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Metadata
- Authors
- Viravaidya, K., Sin, A., & Shuler, M. L.
- Venue
- Biotechnology Progress
- Publisher
- Wiley
- Published
- 2008-09-05
- Volume
- 20
- Issue
- 1
- Pages
- 316-323
- ISSN
- 1520-6033 (ISSN-L)
- 8756-7938
- OpenAlex
- W2139424714
- Cited by
- 305
- References
- 1
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- closed
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