title: 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.
authors.affiliation: School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14850-5201, USA.
authors.forename: Kwanchanok
authors.initials: K
authors.lastname: Viravaidya
authors.forename: Aaron
authors.initials: A
authors.lastname: Sin
authors.forename: Michael L
authors.initials: ML
authors.lastname: Shuler
mesh_terms: D000818:Animals; D032701:Biomimetics / Q000295:instrumentation* / Q000379:methods; D015374:Biosensing Techniques / Q000295:instrumentation* / Q000379:methods; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation / Q000295:instrumentation / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005240:Feasibility Studies; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods; D008904:Miniaturization / Q000379:methods; D009281:Naphthalenes / Q000633:toxicity*; D009928:Organ Specificity; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects*; D013045:Species Specificity
chemical_list: D009281:Naphthalenes; C007229:decalin